Full Text Available Mectizan® has been donated for the control of onchocerciasis for over twenty years, and also for the elimination of lymphatic filariasis for the last ten years. But how much is needed? I
Boatin, Boakye A; Richards, Frank O
Onchocerciasis is a filarial infection which causes blindness and debilitating skin lesions. The disease occurs in 37 countries, of which 30 are found in Africa (the most affected in terms of the distribution and the severity of the clinical manifestations of the disease), six in the Americas and one in the Arabian Peninsula. The latest WHO Expert Committee on Onchocerciasis estimated that in 1995 around 17.7 million persons were infected, about 270,000 of whom were blind and another 500,000 severely visually impaired. The disease is responsible for 1 million DALYs. Eye disease from onchocerciasis accounts for 40% of DALYs annually although severe skin disease is also recognized as of public health significance. Great progress has been made in the last thirty years in the control of onchocerciasis, both in Africa and the Americas, and this progress has been due largely to international public-private partnerships, sustained funding regional programmes, and new tools and technology. Landmarks in the global control of river blindness include the significant success of the Onchocerciasis Control Programme of West Africa (1975-2002), and the donation of ivermectin (Mectizan) by Merck & Co. Inc., in 1988, a medicine that is distributed to millions free of charge each year. Future major technical challenges of onchocerciasis control include ivermectin mass administration in areas co-endemic for the parasite Loa loa in the light of possible severe adverse reactions, ivermectin treatment in hypoendemic areas hitherto excluded from African control programmes, sustainability of ivermectin distribution, post-control surveillance for recrudescence detection, surveillance for emergence of resistance, and decisions of when to stop mass ivermectin treatments. There is the need to develop the appropriate information systems and diagnostic tools to help in accomplishing many of these tasks. A search for a second-line treatment or as an additional drug to ivermectin as well as a
Taylor, H R
Ivermectin is a recently developed macrocyclic lactone that has widespread antiparasitic activity. A series of clinical trials has shown that ivermectin is safe and effective in the treatment of human infection with Onchocerca volvulus. Although it is rapidly microfilaricidal, it does not cause a severe reaction as is seen with diethylcarbamazine treatment. The drug also temporarily interrupts production of microfilaria but has no known long-lasting effects on the adult worms. In patients with onchocerciasis, a single oral dose of ivermectin (150 micrograms/kg) repeated once a year leads to a marked reduction in skin microfilaria counts and ocular involvement. At this dose, ivermectin causes minimal side effects and appears to be sufficiently free of severe adverse reactions to be used on a mass scale. Its use promises to revolutionise the treatment of onchocerciasis.
Van Laethem, Y; Lopes, C
Onchocerciasis ('river blindness') has for several centuries been the scourge of people living in certain areas of the world where the disease is endemic. The treatment available up to 10 years ago, diethylcarbamazine, had very severe secondary effects. The availability of ivermectin--a well tolerated and highly effective microfilaricidal drug--has completely changed this scenario. Ivermectin is now considered to be the drug of choice for the treatment of onchocerciasis. The prognosis for people with onchocerciasis has changed greatly. It is now possible to avoid the heavy infection loads seen previously, and patients, especially expatriates, may have their symptoms relieved by treatment. Ivermectin, used in mass treatment, may also improve the epidemiological situation, reducing the level of microfilariae in the skin of infected people and thus reducing the source for vector infestation. However, the treatment has to be repeated because the drug has no macrofilaricidal effect. Research today is focused on the finding of a drug able to destroy the adult worms that go on producing microfilariae for the length of their lives.
A.P. Plaisier (Anton)
textabstractIn 1990 the World Health Organization (WHO) coordinated Onchocerciasis Control Programme in West Africa (OCP) used this slogan for evaluating fifteen years of control of the parasitic disease onchocerciasis and for expressing its optimism about the future. Based on the obvious success of
in the body of the blackfly and are transmitted to humans when the fly bites ... African Program for Onchocerciasis Control (APOC) in collaboration with the Southern Sudan Onchocerciasis. Task Force carried out Rapid Epidemiological Mapping .... body length. (cm). IVm Dose. Route. 15-25. 90-119. 1 tablet (3mg). Oral once.
Taylor, H R
Ivermectin, a recently developed macrocyclic lactone with broad antiparasitic activity, has been shown by a series of clinical trials to be safe and effective in the treatment of human infection with Onchocerca volvulus. Although it is rapidly microfilaricidal, it does not cause a severe reaction as is seen with diethylcarbamazine treatment. In patients with onchocerciasis, a single oral dose of ivermectin (150 micrograms/Kg) repeated once a year leads to a marked reduction in skin microfilaria counts and ocular involvement, although ivermectin has no known long-lasting effects on the adult worms. With treatment there is no significant exacerbation of either anterior or posterior segment eye disease even in those with severe ocular disease. Treatment leads to a marked and prolonged improvement in ocular status. Because of its safety and efficacy, ivermectin can be used on a mass scale and promises to revolutionize the treatment of onchocerciasis.
Full Text Available Achievements obtained by the onchocerciasis control programmes should not lead to a relaxation in the biological research on Onchocerca volvulus. Issues such as the Loa loa-related postivermectin serious adverse events, the uncertainties as to whether onchocerciasis can be eliminated by ivermectin treatments, and the possible emergence of ivermectin-resistant O. volvulus populations should be addressed proactively. Doxycycline, moxidectin and emodepside appear to be promising as alternative drugs against onchocerciasis but support to researches in immunology and genomics should also be increased to develop new control tools, including both vaccines and macrofilaricidal drugs.
Mahoney, J L
During a 12-month period (1977 - 1978) of employment in the river forest area of the Ivory Coast, an isolated area hyperendemic for onchocerciasis, a unique opportunity arose to study the disease in depth. Personal observations and experiences with the disease did not necessarily correlate with textbook statements. Although onchocerciasis may involve almost any area of the body it more commonly involves the skin, eyes, lymphatics and groin area. The disease does not appear to cause premature or direct death, but is often acutely and chronically disabling. Diethylcarbamazine and suramin are effective in preventing disabling complications and in diminishing or controlling the progression of complications, but are nephrotoxic. Surgery is utilized to excise microfilaria-producing nodules in order to minimize or control disease progression and for the repair of the frequently occurring complication of inguinal or femoral hernias and hydroceles. A high percentage of patients had microfilarial eye infiltrates but blindness was uncommon. The disease should therefore be known as 'river eye disease' rather than the current 'river blindness'. There is no known method of effective prevention of the disease that is acceptable on a long-term basis.
The Habitat and Behavioural Environment of Onchocerciasis in Patigi Local ... physical and socio-economic factors of vulnerability to onchocerciasis in Patigi ... from its effects on the human body, ..... population and cultural behaviour forms.
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Mackenzie, Charles D; Homeida, Mamoun M; Hopkins, Adrian D; Lawrence, Joni C
Human onchocerciasis, a parasitic disease found in 28 African countries, six Latin American countries and Yemen, causes blindness and severe dermatological problems. In 1987, efforts to control this infection shifted from vector approaches to include the mass distribution of ivermectin - a drug donated by Merck & Co. for disease control in Africa and for disease elimination in the Americas. Currently, almost 25 years later, with the Americas being highly successful and now approaching elimination, new evidence points towards the possibility of successful elimination in Africa. We suggest several major changes in the programmatic approach that through focused goal-directed effort could achieve global elimination of onchocerciasis by 2025.
Mario A Rodríguez-Pérez
Full Text Available Mexico is one of the six countries formerly endemic for onchocerciasis in Latin America. Transmission has been interrupted in the three endemic foci of that country and mass drug distribution has ceased. Three years after mass drug distribution ended, post-treatment surveillance (PTS surveys were undertaken which employed entomological indicators to check for transmission recrudescence.In-depth entomologic assessments were performed in 18 communities in the three endemic foci of Mexico. None of the 108,212 Simulium ochraceum s.l. collected from the three foci were found to contain parasite DNA when tested by polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA, resulting in a maximum upper bound of the 95% confidence interval (95%-ULCI of the infective rate in the vectors of 0.035/2,000 flies examined. This is an order of magnitude below the threshold of a 95%-ULCI of less than one infective fly per 2,000 flies tested, the current entomological criterion for interruption of transmission developed by the international community. The point estimate of seasonal transmission potential (STP was zero, and the upper bound of the 95% confidence interval for the STP ranged from 1.2 to 1.7 L3/person/season in the different foci. This value is below all previous estimates for the minimum transmission potential required to maintain the parasite population.The results from the in-depth entomological post treatment surveillance surveys strongly suggest that transmission has not resumed in the three foci of Mexico during the three years since the last distribution of ivermectin occurred; it was concluded that transmission remains undetectable without intervention, and Onchocerca volvulus has been eliminated from Mexico.
Richards, F; Hopkins, D; Cupp, E
Onchocerciasis is an endemic disease in 37 countries (in Africa, in the Americas, and in Yemen). It infects at least 17.7 million people and causes visual impairment in 500,000 and blindness in another 270,000. It is transmitted by black flies that breed in rapidly flowing rivers and streams. As response to an endemic disease, programs have focused on the control of onchocerciasis transmission. In Africa, the African Programme for Onchocerciasis Control is based on an ivermectin-distribution strategy designed to control the skin and eye disorders that result from heavy infections. By contrast, the strategy of the African Onchocerciasis Control Program is a vector control to completely interrupt the transmission cycle of the parasite by applying larvicide to riverine breeding sites. In the Americas, another strategy being implemented is to use ivermectin more than once a year, not only to stop progression of disease, but also to interrupt transmission. Moreover, the global lymphatic-filariasis initiative aims to halt transmission of lymphatic filariasis in endemic African communities by annual mass administration of single-dose combination therapy with albendazole and Mectizan.
Ronald H. Guderian
Full Text Available Details are given of the prevalence rates of onchocerciasis from the most recent surveys (1989 conducted in northern Ecuador. The disease has intensified and dispersed considerably due to migration of infected individuals and the presence of a highly efficient vector. Comparison of these data with those from two previous surveys carried out in 1982/83 and 1986 and correlated with entomological findings highly the danger of the formation of new foci of onchocerciasis in areas currently free of the disease. Recommendations are made for further entomological studies in areas either recently or likely to be affected by the disease where potential vectors are unknown or different to those registred in the Santiago focus. Invermectin treatment with local vector control in specific areas is advocated to reduce the disease to a low level of public health importance.
Aziz, M A
Onchocerciasis is one of the leading causes of blindness in the developing world. An estimated 40 million people are afflicted with this parasitic disease. World Health Organization vector control programs have had considerable success in interrupting the parasite transmission cycle in selected savanna regions of West Africa, but chemotherapeutic agents suitable for massive treatment campaigns have not been available. Controlled clinical studies have indicated that a single oral dose of ivermectin is safer and more effective therapy for onchocerciasis than the the standard seven- to 10-day course of diethylcarbamazine, the current drug of choice, and that ivermectin causes a more prolonged reduction in dermal microfilarial density. Patients treated with ivermectin are unable to infect the blackfly vector as long as the dermal microfilarial density remains low; therefore, once- or twice-yearly administration of ivermectin in community-wide therapy programs, either alone or in combination with vector control measures, may successfully interrupt transmission of the parasite and eventually eliminate the disease.
Donnelly, J J; Rockey, J H; Bianco, A E; Soulsby, E J
Ocular immunopathologic responses of inbred guinea pigs infected with Onchocerca microfilariae from domesticated animals were studied as a laboratory model of human ocular onchocerciasis. A single intracorneal infection of normal guinea pigs with microfilariae produced only minimal ocular lesions. In contrast, intracorneal infection of guinea pigs previously immunized by systemic infection with microfilariae produced intense corneal and uveal inflammation. Transfer of splenic lymphocytes from immunized donors to syngeneic normal recipients substituted effectively for the active immunization. Cell recipients produced marked corneal inflammatory reactions when challenged by a single intracorneal infection. Fresh and cryopreserved microfilariae produced identical reactions. The corneal inflammatory infiltrates were composed primarily of eosinophils, neutrophils, and plasma cells and resembled human onchocercal keratitis. Diethylcarbamazine citrate administration after a challenge intracorneal infection increased the severity of the corneal inflammatory response in immunized animals.
Brandling-Bennett, A D; Darsie, R F
Ten Simulium ochraceum were allowed to feed at 10 different sites on 12 Guatemalans with onchocerciasis, and skin snips were taken from six of these sites. Numbers of microfilariae (mff) ingested by the flies and mff emerging from skin snips were highly correlated and showed that concentrations were greatest on the torso and decreased peripherally. S. ochraceum ingested the number of mff present in 1.0 mg or under 1.5 mm2 of skin. Numbers of mff in skin snips from the head, shoulder and upper arm correlated with over-all levels of infection but were frequently negative in subjects with light infections. Two or more skin snips were best able to detect and quantify infections.
Duke, B O
The general characteristics of Onchocerca volvulus infection and its transmission are outlined in this overview of human onchocerciasis. The pathogenic role of the microfilariae, producing lesions of the skin, lymphatic system, eye and deep organs, are described, along with the main clinical manifestations of the disease. The global prevalence and distribution of onchocerciasis are given. Best estimates in 1985 gave 86 million persons at risk, 17.8 million infected, 336,400 blind and a like number suffering from severe visual impairment. The vast majority was in Africa. The impact of onchocerciasis on communities in the Sudano-Guinean savanna zone of Africa is outlined, emphasizing the very high blindness rates and the increased mortality among the blind. Communities so affected cannot remain economically viable. They are forced to desert their villages and the fertile land near rivers. The background to the establishment of the Onchocerciasis Control Programme in West Africa (OCP) is given and the successful 10-year results of this campaign, which is based on prolonged, regular Simulium larviciding, are outlined. In the context of the future of the OCP and of the control of onchocerciasis elsewhere in the world, the need for improved chemotherapy is discussed. The prospects for large-scale suppressive therapy have greatly improved following the registration of ivermectin in 1988 for use in human onchocerciasis. The potential and possible uses of this drug, as a single-dose, non-toxic microfilaricide, which excites very little Mazzotti reaction and has a prolonged microfilarial suppressant action, are discussed. It is considered that an effective non-toxic macrofilaricide is still a prime need for onchocerciasis control.
Full Text Available Abstract Onchocerciasis (river blindness is a blinding parasitic disease that threatens the health of approximately 120 million people worldwide. While 99% of the population at-risk for infection from onchocerciasis live in Africa, some 500,000 people in the Americas are also threatened by infection. A relatively recent arrival to the western hemisphere, onchocerciasis was brought to the New World through the slave trade and spread through migration. The centuries since its arrival have seen advances in diagnosing, mapping and treating the disease. Once endemic to six countries in the Americas (Brazil, Colombia, Ecuador, Guatemala, Mexico and Venezuela, onchocerciasis is on track for interruption of transmission in the Americas by 2012, in line with Pan American Health Organization resolution CD48.R12. The success of this public health program is due to a robust public-private partnership involving national governments, local communities, donor organizations, intergovernmental bodies, academic institutions, non-profit organizations and the pharmaceutical industry. The lessons learned through the efforts in the Americas are in turn informing the program to control and eliminate onchocerciasis in Africa. However, continued support and investment are needed for program implementation and post-treatment surveillance to protect the gains to-date and ensure complete elimination is achieved and treatment can be safely stopped within all 13 regional foci.
Sam-Wobo, S O; Adeleke, M A; Jayeola, O A; Adeyi, A O; Oluwole, A S; Ikenga, M; Lawniye, F; Gazama, J; Kagni, A; Kosoko, T O; Agbeyangi, O; Bankole, S; Toé, L; Mafiana, C F; Yameogo, L
Epidemiological studies were carried out to assess the prevalence and community microfilarial load (CMFL) of onchocerciasis after repeated annual treatment with ivermectin along Ogun river System, southwest Nigeria. Skin snips were taken from consented participants in 11 selected communities along the River system. The microfilarial load of the community was estimated. The prevalence and CMFL varied significantly in the communities (p <0.05). The prevalence of onchocerciasis ranged from 19.1 to 45.6%, while the CMFL ranged from 0.11 to 1.03 microfilariae per skin snip. The CMFL recorded was <5 microfilariae per skin snip, i.e. recognized by WHO as threshold value in certifying the communities to be free of onchocerciasis as public health problem, thus, signifying the possibility of onchocerciasis elimination in the study area. Efforts should therefore be intensified to achieve improved ivermectin coverage and compliance in annual ivermectin treatment in order to completely eliminate onchocerciasis as a public health problem in the studied communities.
Taylor, H R; Murphy, R P; Newland, H S; White, A T; D'Anna, S A; Keyvan-Larijani, E; Aziz, M A; Cupp, E W; Greene, B M
The ocular changes that occur with diethylcarbamazine treatment of onchocerciasis seriously restrict its usefulness. Ivermectin, a newly developed antifilarial drug, was compared with diethylcarbamazine for treatment of onchocerciasis in a double-masked, placebo-controlled trial. Thirty men with moderate to severe infection and ocular involvement were randomly assigned to receive ivermectin as a single oral dose (200 micrograms/kg), diethylcarbamazine (administered for eight days), or placebo. Detailed ocular examinations were performed serially over a 12-month period. Diethylcarbamazine treatment caused a marked increase in living and dead microfilariae in the cornea, punctate opacities, and limbitis during the first week of therapy. Ivermectin had no such effect. However, ivermectin therapy resulted in a long-term reduction in intraocular microfilariae comparable to that seen with diethylcarbamazine. Ivermectin appears to have few ocular complications and be a better-tolerated and more effective microfilaricidal agent than diethylcarbamazine for the treatment of onchocerciasis.
Anderson, J; Fuglsang, H; de C Marshall, T F
A single 10-14 day course of diethylcarbamazine (DEC) was given under betamethazone cover to 18 patients (Group A) with ocular onchocerciasis, and the effects were studied in detail over 1-2 years. A comparison was made with the findings in 21 patients (Group B) who received a similar course to be followed by a weekly suppressive 100-200 mg dose of DEC. A further 18 patients (Group C) served as controls. The initial DEC course provoked severe general reactions, but ocular complications could be controlled by betamethazone. The weekly suppressive dose was not acceptable to the majority of patients, and only one young patient with severe iritis who improved during the initial course took the weekly tablet voluntarily over 2 years. The initial DEC course reduced the numbers of microfilariae in the eye and was of temporary benefit to lesions of the anterior segment, but it did not affect lesions of the posterior segment. A possible adverse effect on the optic disc is discussed. Any beneficial long term effect was almost confined to Group B, and to lesions of the anterior segment. The best to hope for in lesions of the posterior segment was arrest of further development. The findings at the end of the trial were as follows: No. of lesions (see article).
Anderson, J; Fuglsang, H; de C Marshall, T F
39 patients (Group A) with ocular onchocerciasis in the Sudan-savanna of north Cameroon were given 4-6 g of suramin and followed in detail over 1-2 years. 39 other patients (Group B) received suramin followed 2 weeks later by a 6-7 day course of diethylcarbamazine (DEC). A further 18 patients (Group C) received placebo injections and were followed in the same way by the same observers. Suramin caused serious general reactions among the 100 patients who started the course - 1 case of stomatitis, 1 exfoliative dermatitis, and several cases of severe prostration, among which 2 ended fatally. These reactions underline the urgency for further studies on the toxicity of suramin, which is without doubt an efficient macro- and micro-filaricidal drug. Changes which occurred in the ocular lesions are described in detail. There was an initial aggravation of punctate and sclerosing keratitis, and sometimes a serious aggravation or development of anterior uveitis, corresponding to the peak microfilaricidal effect of the drug. The possibility of a simultaneous adverse effect on the optic disc is discussed. Despite these reactions, which might have been avoided by prior elimination of microfilariae by DEC, the eyes were in general quieter at 3 months and thereafter than before treatment. However, no posterior segment lesion improved after suramin, and the majority remained unchanged. The findings at the end of the trial were as follows: No. of lesions (see article).
S.O. Sam-Wobo , M.A. Adeleke , O.A. Jayeola , A.O. Adeyi , A.S. Oluwole , M. Ikenga , A. Lawniye , J. Gazama , A. Kagni , T.O. Kosoko , O. Agbeyangi , S. Bankole , L. Toé , C.F. Mafiana & L. Yameogo
Full Text Available Background & objective: Epidemiological studies were carried out to assess the prevalence and communitymicrofilarial load (CMFL of onchocerciasis after repeated annual treatment with ivermectin along Ogun riverSystem, southwest Nigeria.Method: Skin snips were taken from consented participants in 11 selected communities along the River system.The microfilarial load of the community was estimated.Results: The prevalence and CMFL varied significantly in the communities (p <0.05. The prevalence ofonchocerciasis ranged from 19.1 to 45.6%, while the CMFL ranged from 0.11 to 1.03 microfilariae per skinsnip. The CMFL recorded was <5 microfilariae per skin snip, i.e. recognized by WHO as threshold value incertifying the communities to be free of onchocerciasis as public health problem, thus, signifying the possibilityof onchocerciasis elimination in the study area.Conclusion: Efforts should therefore be intensified to achieve improved ivermectin coverage and compliance inannual ivermectin treatment in order to completely eliminate onchocerciasis as a public health problem in thestudied communities.
textabstractThe present thesis deals with research which has been undertaken since 1983 with the aim of finding answers to the three main epidemiological questions which have been discussed above, i.e. I.-What are the epidemiological patterns of ocular onchocerciasis in West Africa and what is the g
Rodríguez-Pérez, Mario A; Unnasch, Thomas R; Real-Najarro, Olga
Onchocerciasis has historically been one of the leading causes of infectious blindness worldwide. It is endemic to tropical regions both in Africa and Latin America and in the Yemen. In Latin America, it is found in 13 foci located in 6 different countries. The epidemiologically most important focus of onchocerciasis in the Americas is located in a region spanning the border between Guatemala and Mexico. However, the Amazonian focus straddling the border of Venezuela and Brazil is larger in overall area because the Yanomami populations are scattered over a very large geographical region. Onchocerciasis is caused by infection with the filarial parasite Onchocerca volvulus. The infection is spread through the bites of an insect vector, black flies of the genus Simulium. In Africa, the major vectors are members of the S. damnosum complex, while numerous species serve as vectors of the parasite in Latin America. Latin America has had a long history of attempts to control onchocerciasis, stretching back almost 100 years. The earliest programmes used a strategy of surgical removal of the adult parasites from affected individuals. However, because many of the adult parasites lodge in undetectable and inaccessible areas of the body, the overall effect of this strategy on the prevalence of infection was relatively minor. In 1988, a new drug, ivermectin, was introduced that effectively killed the larval stage (microfilaria) of the parasite in infected humans. As the microfilaria is both the stage that is transmitted by the vector fly and the cause of most of the pathologies associated with the infection, ivermectin opened up a new strategy for the control of onchocerciasis. Concurrent with the use of ivermectin for the treatment of onchocerciasis, a number of sensitive new diagnostic tools were developed (both serological and nucleic acid based) that provided the efficiency, sensitivity and specificity necessary to monitor the decline and eventual elimination of
Annette C. Kuesel
Full Text Available Onchocerciasis is a parasitic, vector borne disease caused by the filarial nematode Onchocerca volvulus. More than 99% of the population at risk of infection live in Africa. Onchocerciasis control was initiated in West Africa in 1974 with vector control, later complemented by ivermectin mass drug administration and in the other African endemic countries in 1995 with annual community directed treatment with ivermectin (CDTI. This has significantly reduced infection prevalence. Together with proof-of-concept for onchocerciasis elimination with annual CDTI from foci in Senegal and Mali, this has resulted in targeting onchocerciasis elimination in selected African countries by 2020 and in 80% of African countries by 2025. The challenges for meeting these targets include the number of endemic countries where conflict has delayed or interrupted control programmes, cross-border foci, potential emergence of parasite strains with low susceptibility to ivermectin and co-endemicity of loiasis, another parasitic vector borne disease, which slows down or prohibits CDTI implementation. Some of these challenges could be addressed with new drugs or drug combinations with a higher effect on Onchocerca volvulus than ivermectin. This paper reviews the path from discovery of new compounds to their qualification for large scale use and the support regulatory authorities provide for development of drugs for neglected tropical diseases. The status of research for new drugs or treatment regimens for onchocerciasis along the path to regulatory approval and qualification for large scale use is reviewed. This research includes new regimens and combinations of ivermectin and albendazole, antibiotics targeting the O. volvulus endosymbiont Wolbachia, flubendazole, moxidectin and emodepside and discovery of new compounds.
Kuesel, Annette C
Onchocerciasis is a parasitic, vector borne disease caused by the filarial nematode Onchocerca volvulus. More than 99% of the population at risk of infection live in Africa. Onchocerciasis control was initiated in West Africa in 1974 with vector control, later complemented by ivermectin mass drug administration and in the other African endemic countries in 1995 with annual community directed treatment with ivermectin (CDTI.) This has significantly reduced infection prevalence. Together with proof-of-concept for onchocerciasis elimination with annual CDTI from foci in Senegal and Mali, this has resulted in targeting onchocerciasis elimination in selected African countries by 2020 and in 80% of African countries by 2025. The challenges for meeting these targets include the number of endemic countries where conflict has delayed or interrupted control programmes, cross-border foci, potential emergence of parasite strains with low susceptibility to ivermectin and co-endemicity of loiasis, another parasitic vector borne disease, which slows down or prohibits CDTI implementation. Some of these challenges could be addressed with new drugs or drug combinations with a higher effect on Onchocerca volvulus than ivermectin. This paper reviews the path from discovery of new compounds to their qualification for large scale use and the support regulatory authorities provide for development of drugs for neglected tropical diseases. The status of research for new drugs or treatment regimens for onchocerciasis along the path to regulatory approval and qualification for large scale use is reviewed. This research includes new regimens and combinations of ivermectin and albendazole, antibiotics targeting the O. volvulus endosymbiont Wolbachia, flubendazole, moxidectin and emodepside and discovery of new compounds.
Krotneva, Stanimira P; Coffeng, Luc E; Noma, Mounkaila; Zouré, Honorat G M; Bakoné, Lalle; Amazigo, Uche V; de Vlas, Sake J; Stolk, Wilma A
Since its initiation in 1995, the African Program for Onchocerciasis Control (APOC) has had a substantial impact on the prevalence and burden of onchocerciasis through annual ivermectin mass treatment...
Taylor, H R; Semba, R D; Newland, H S; Keyvan-Larijani, E; White, A; Dukuly, Z; Greene, B M
The treatment of onchocerciasis with diethylcarbamazine and suramin is associated with an exacerbation of ocular disease. This occurs more frequently in patients with severe onchocercal ocular disease. We assessed ocular changes following ivermectin treatment in 39 patients with severe ocular onchocerciasis. Patients were treated with 100, 150, or 200 micrograms/kg of ivermectin at either 1 or 2 year intervals and followed for 3 years. There was no evidence for an acute exacerbation of either anterior or posterior segment eye disease, and there was a marked improvement in ocular status in the group as a whole. There was a significant decrease in onchocercal involvement which was maintained for at least 3 years. Annual treatment with ivermectin can be used safely in patients with severe ocular disease and is beneficial over a prolonged period of time.
Taylor, H R; Greene, B M
Ivermectin is a macrocyclic lactone that has widespread antiparasitic activity. Numerous clinical trials have shown that ivermectin is safe and effective in the treatment of human infection with Onchocerca volvulus. Although it is rapidly microfilaricidal, it does not cause a severe reaction, as is seen with diethylcarbamazine treatment. The drug temporarily interrupts production of microfilaria but has not known long-lasting effects on the adult worms. In patients with onchocerciasis, a single oral dose of ivermectin (150 micrograms/kg) repeated once a year leads to a marked reduction in skin microfilaria counts and ocular involvement. At this dose, ivermectin causes minimal side effects and is sufficiently free of severe reactions to be used on a mass scale. It promises to revolutionize the treatment of onchocerciasis.
Ottesen, E A
It is not clear what role immediate hypersensitivity immune responses have in the pathogenesis of human onchocerciasis, but it is certain that these responses are prominent both in the course of natural infection and during the Mazzotti reactions that follow treatment with diethylcarbamazine. In humans, the levels of total serum IgE associated with onchocerciasis are as high or higher than those associated with almost any helminth infection, although specific IgE antibodies to Onchocerca volvulus appear to be a small and still poorly characterized fraction of the total serum IgE. Evidence about the relationship of these prominent IgE responses in patients with onchocerciasis to the onchocercal skin disease that manifests as pruritus and papular eruptions is conflicting, but in a guinea pig model of ocular pathology induced by onchocerca microfilariae evidence for the pathogenetic importance of IgE and immediate hypersensitivity is much less equivocal. The suggestive findings from this model make it imperative to carry out similar studies of Onchocerca-affected human eyes to determine whether immediate hypersensitivity responses play a similar critical role in the pathogenesis of the ocular lesions in humans.
L.E. Coffeng (Luc); W.A. Stolk (Wilma); H.G.M. Zouré (Honorat G.); J.L. Veerman (Lennert); K.B. Agblewonu (Koffi); M.E. Murdoch (Michele); M. Noma (Mounkaila); G. Fobi (Grace); J.H. Richardus (Jan Hendrik); D.A.P. Bundy (Donald A.); J.D.F. Habbema (Dik); S.J. de Vlas (Sake); U.V. Amazigo (Uche)
textabstractBackground: Onchocerciasis causes a considerable disease burden in Africa, mainly through skin and eye disease. Since 1995, the African Programme for Onchocerciasis Control (APOC) has coordinated annual mass treatment with ivermectin in 16 countries. In this study, we estimate the health
Dieye, Yakou; Storey, Helen L; Barrett, Kelsey L; Gerth-Guyette, Emily; Di Giorgio, Laura; Golden, Allison; Faulx, Dunia; Kalnoky, Michael; Ndiaye, Marie Khemesse Ngom; Sy, Ngayo; Mané, Malang; Faye, Babacar; Sarr, Mamadou; Dioukhane, Elhadji Mamadou; Peck, Roger B; Guinot, Philippe; de Los Santos, Tala
As effective onchocerciasis control efforts in Africa transition to elimination efforts, different diagnostic tools are required to support country programs. Senegal, with its long standing, successful control program, is transitioning to using the SD BIOLINE Onchocerciasis IgG4 (Ov16) rapid test over traditional skin snip microscopy. The aim of this study is to demonstrate the feasibility of integrating the Ov16 rapid test into onchocerciasis surveillance activities in Senegal, based on the following attributes of acceptability, usability, and cost. A cross-sectional study was conducted in 13 villages in southeastern Senegal in May 2016. Individuals 5 years and older were invited to participate in a demographic questionnaire, an Ov16 rapid test, a skin snip biopsy, and an acceptability interview. Rapid test technicians were interviewed and a costing analysis was conducted. Of 1,173 participants, 1,169 (99.7%) agreed to the rapid test while 383 (32.7%) agreed to skin snip microscopy. The sero-positivity rate of the rapid test among those tested was 2.6% with zero positives 10 years and younger. None of the 383 skin snips were positive for Ov microfilaria. Community members appreciated that the rapid test was performed quickly, was not painful, and provided reliable results. The total costs for this surveillance activity was $22,272.83, with a cost per test conducted at $3.14 for rapid test, $7.58 for skin snip microscopy, and $13.43 for shared costs. If no participants had refused skin snip microscopy, the total cost per method with shared costs would have been around $16 per person tested. In this area with low onchocerciasis sero-positivity, there was high acceptability and perceived value of the rapid test by community members and technicians. This study provides evidence of the feasibility of implementing the Ov16 rapid test in Senegal and may be informative to other country programs transitioning to Ov16 serologic tools.
Awadzi, K; Dadzie, K Y; Shulz-Key, H; Haddock, D R; Gilles, H M; Aziz, M A
Nineteen patients from an area of vector control in the savanna region of Northern Ghana, all with moderate to heavy infections with Onchocerca volvulus and some with ocular involvement, were treated with 50, 100, 150 or 200 micrograms kg-1 of ivermectin. Detailed monitoring of clinical and ocular reactions and of alterations in skin microfilarial counts and laboratory indices were carried out during the first 28 days. Microfilarial counts in skin snips and detailed ocular examinations were then repeated at intervals over a period of nine months. Ivermectin slowly eliminated microfilariae from the skin and eye without serious adverse clinical or ocular reactions in all treated groups. There was little difference in efficacy between doses of 100, 150 and 200 micrograms kg-1, and these were more effective than the 50 micrograms kg-1 dose. Very low levels of skin microfilariae were maintained for nine months. Microfilariae were not eliminated from the eye for at least three months. The drug was neither macrofilaricidal nor embryotoxic. However, it produced a dose-dependent stimulation of embryogenesis manifest at one month and succeeded by a suppression of embryogenesis at three months after therapy. In areas where transmission of onchocerciasis has been interrupted, ivermectin may need not be given more often than once a year. The efficacy of the drug on single dosage and the mild adverse reactions produced, if confirmed in subsequent controlled studies, would greatly simplify the treatment of onchocerciasis and would reintroduce new concepts of the role of chemotherapy in the control of onchocerciasis.
Van der Lelij, A; Rothova, A; Klaassen-Broekema, N; Wilson, W R; Barbe, R F; Stilma, J S
We assessed the side-effects after multiple single-dose treatment with ivermectin (150 micrograms/kg) in onchocerciasis patients form a hyperendemic area in Sierra Leone, in order to investigate whether medical surveillance was always necessary. After initial treatment 87 onchocerciasis patients were examined for adverse reactions. Fourty-four of these 87 patients (51%) received a second dose of ivermectin 5 months later and thirty-five (40%) received a third dose one year later. The side-effects after the second and third doses were significantly diminished, when compared with the initial dose of ivermectin in the treatment of onchocerciasis (chi2 test p less than 0.005, resp. p less than 0.008). Side-effects requiring therapy were observed in 32% of patients after the first dose, in 18% after the second dose and in 11% after the third dose of ivermectin. Severe side-effects (9%) were only seen after the initial ivermectin dose. All the severe adverse reactions appeared within 48 hours. In view of our findings, it seems necessary that the first treatment with ivermectin should take place under strict medical supervision during at least two days. Five months after treatment with a single dose of ivermectin 29 out of 44 patients (66%) still had a positive skin-snip test. Seven months after the second dose 15 of 35 patients (43%) had a positive skin-snip count. Since almost half of the patients had a positive skin-snip test despite two treatments with ivermectin, it could be argued that in hyperendemic areas treatment should consist of at least two doses in the first year.
Chippaux, J P; Boussinesq, M; Prod'hon, J
Onchocerciasis is an infection with the nematode Onchocerca volvulus. The main clinical symptoms are caused by the microfilariae. They include ocular lesions leading to blindness. Onchocerciasis is widely distributed in Africa from the Sahara to the southern tip, and is also found in some areas of South and Central America. Ivermectin was shown to be an effective treatment in the early 1980's, and is safe and better tolerated than diethylcarbamazine. We report the results of ivermectin treatment of onchocerciasis, and various features of the control obtained by large-scale ivermectin treatment programs. In large-scale programs, ivermectin (150 micrograms/kg) is administered once a year. This dose paralyses the microfilariae, such that they are carried away by the lymph to the lymph nodes where they are destroyed. This dose thereby reduces the load of microfilaria by 90%. The effects of a dose of ivermectin last about two or three years, and the lesions in the anterior segment of the eye can be cured or substantially reduced. Regular treatment prevents severe lesions of the posterior segment of the eye. The effects of repeated treatment on lesions of the retina are currently under investigation. Frequent doses of ivermectin prevent the development of embryo parasites in the females, and reduces the number of adults by attrition. Large-scale treatment programs reduce the transmission of the parasite by its vectors. There are several problems impeding large-scale treatment programs. Choosing patients for priority treatment requires expensive and sometimes aggressive methods of diagnosis. Thus new techniques for the identification of communities in which onchocerciasis is a serious public health problem are required. The choice of strategies for distribution, to optimize the cost, benefit ratio and feasibility, remain controversial. Wide distribution by mobile teams is effective, but expensive. Active distribution by trained community distributors is a cheaper
Full Text Available Tarig B Higazi,1 Timothy G Geary,2 Charles D Mackenzie3,41Department of Biological Sciences, Ohio University Zanesville, Zanesville, OH, USA; 2Institute of Parasitology, McGill University, Montreal, QC, Canada; 3Center for Neglected Tropical Diseases, Liverpool School of Tropical Medicine, Liverpool, UK; 4Department of Pathobiology & Diagnostic Investigation, Michigan State University, East Lansing, MI, USAAbstract: Onchocerciasis treatment is one of the most positive stories in tropical medicine although major challenges remain to reaching the ultimate goal of disease elimination. Such challenges are to be expected when the therapeutic goal is to kill and safely remove a large multistage, efficient, metazoan infectious agent such as Onchocerca volvulus that has an exceptionally complicated relationship with its host. Successful control of onchocerciasis has often been hampered by host reactions following chemotherapy, that can sometimes cause significant tissue pathology. Presence of other filariae, particularly Loa loa, in endemic onchocerciasis-treatment areas also poses severe problems due to adverse reactions caused by drug-induced death of the coincident microfilariae of this usually clinically benign species. Although ivermectin has been very successful, there is a need to enhance the progress toward elimination of onchocerciasis; new drugs and their efficient use are keys to this. The permanent absence of Onchocerca microfilaridermia, defined as the lack of resurgence of skin microfilarial loads after treatment, is the ultimate characteristic of a useful new chemotherapeutic agent. Several drugs are under investigation to achieve this, including the reassessment of currently available and previously tested agents, such as the antibiotic, doxycycline, which targets the adult parasites through its anti-Wolbachia endosymbiont activity. Flubendazole, a benzimidazole derivative approved for treatment of human gastrointestinal nematodes, is
Greene, B M; Taylor, H R; Cupp, E W; Murphy, R P; White, A T; Aziz, M A; Schulz-Key, H; D'Anna, S A; Newland, H S; Goldschmidt, L P
We compared ivermectin with diethylcarbamazine for the treatment of onchocerciasis in a double-blind, placebo-controlled trial. Thirty men with moderate to heavy infection and ocular involvement were randomly assigned to receive ivermectin in a single oral dose (200 micrograms per kilogram of body weight), diethylcarbamazine daily for eight days, or placebo. Diethylcarbamazine caused a significantly more severe systemic reaction than ivermectin (P less than 0.001), whereas the reaction to ivermectin did not differ from the reaction to placebo. Diethylcarbamazine markedly increased the number of punctate opacities in the eye (P less than 0.001), as well as the number of dead and living microfilariae in the cornea over the first week of therapy. Ivermectin had no such effect. Both ivermectin and diethylcarbamazine promptly reduced skin microfilaria counts, but only in the ivermectin group did counts remain significantly lower (P less than 0.005) than in the placebo group at the end of six months of observation. Analysis of adult worms isolated from nodules obtained two months after the start of therapy showed no effect of either drug on viability. Ivermectin appears to be a better tolerated, safer, and more effective microfilaricidal agent than diethylcarbamazine for the treatment of onchocerciasis.
Tielsch, James M; Beeche, Arlyne
The Onchocerciasis Control Program (OCP), one of the most successful vertical disease control programs in the history of public health, came to an end in 2003 with devolvement of responsibilities for control program activities passed to the countries affected. Fortunately, 15 years ago the Mectizan Distribution Program (MDP) was founded to provide a complementary approach to controlling the disabling consequences of this parasitic infection. With over 250 million doses of ivermectin distributed over the past 15 years, the MDP is well on its way to both solidifying the progress made by the OCP and extending program reach well beyond the boundaries of the OCP. Through the extensive clinical testing protocols implemented in a variety of countries in Aftica, ivermectin has been proven to be a safe and highly effective treatment for onchocerciasis. Regular distribution to populations living in endemic areas has demonstrated significant reductions in blinding ocular complications, transmission, and disability caused by onchocercal skin disease. As yet undocumented, are the likely significant impact regular population dosing with ivermectin has on intestinal helminth infections, lymphatic filariasis, and human scabies infection. While there are significant barriers to continued program success, focussed attention on expanding and improving community-directed ivermectin distribution is likely to lead to further progress against this resilient infection.
Brown, K R; Neu, D C
Initial clinical trials with ivermectin were performed in patients with both roundworm infestation and onchocerciasis. Obvious clinical safety allowed for rapid progression through 5-30-50-100-150-200 mcg/kg in infected patients. Initial studies showed some effect at 50 mcg/kg; subsequent double-blind controlled studies, either with placebo or diethylcarbamazine (DEC), confirmed the efficacy of ivermectin as well as further defining its safety profile. Absence of adverse eye findings or serious systemic reactions justified the further open trials. Studies of patients treated at 6, 12, or 18 month intervals showed a long lasting effect of ivermectin in reducing skin microfilaria counts. Phase III studies confirmed safety and efficacy and further refined the dose to 150 mcg/kg every 12 months. Large trials in Liberia and other countries in West Africa, and subsequently under Onchocerciasis Control Program (OCP), included approximately 120,000 persons carefully followed during which few patients with serious adverse experiences were reported. These extensive field trials confirmed the relative safety allowing for broad distribution of ivermectin in programs not able to provide physician monitoring.
Umeh, R E; Mahmoud, A O; Hagan, M; Wilson, M; Okoye, O I; Asana, U; Biritwum, R; Ogbu-Pearce, P; Elhassan, E; Yaméogo, L; Braideo, E I; Seketeli, A
The African Programme for Onchocerciasis Control (APOC) sponsored a baseline study in Nigeria between 1998 and 1999 on the prevalence and distribution of Onchocerciasis. The randomly selected 1,064 subjects in the baseline study underwent detailed eye examination in Cross River (rain forest), Taraba (savanna) and Kogi (forest-savanna) States. This paper compares and contrasts the public health significance of ocular onchocerciasis in these ecological zones. A blindness prevalence of 2.4% was recorded in the study, onchocerciasis being responsible for 30.2% of the bilaterally blind subjects. Onchocerciasis-induced blindness prevalence was relatively high in the rain forest and forest savanna zones of Cross River and Kogi States, Cross River having the highest site-specific prevalence (50.0%), followed by Kogi (41.7%). Taraba recorded only 27.3%. Other conditions identified included glaucoma, optic nerve disease and cataract rates of which were also found to be high among the population (6.9%, 6.5 % and 8.9% respectively). Anterior segment onchocercal lesions, punctate and sclerosing keratitis were the predominant features of the infection in the savanna zone (14.1% and 6.3% respectively), while posterior segment lesions were much more common in the forest zone. The need to sustain the present efforts to control onchocerciasis through mass ivermectin treatment is recommended.
Wanji, Samuel; Tendongfor, Nicholas; Nji, Theolbald; Esum, Mathias; Che, Julious N; Nkwescheu, Armand; Alassa, Fifen; Kamnang, Geremy; Enyong, Peter A; Taylor, Mark J; Hoerauf, Achim; Taylor, David W
Severe side effects following ivermectin treatment of onchocerciasis in areas of co-endemicity with loaisis have been an impediment for the work of the African Programme for Onchocerciasis Control (APOC...
Stanimira P Krotneva; Luc E Coffeng; Mounkaila Noma; Honorat G M Zouré; Lalle Bakoné; Uche V Amazigo; Sake J de Vlas; Wilma A Stolk
Since its initiation in 1995, the African Program for Onchocerciasis Control (APOC) has had a substantial impact on the prevalence and burden of onchocerciasis through annual ivermectin mass treatment...
Fulford, A J; Macfarlane, S B; Awadzi, K; Bell, D R; Gilles, H M
This paper presents some statistical problems of analysing changes in patterns of microfilarial loads in onchocerciasis patients after chemotherapeutic treatment. Analyses are made of a pooled set of data from ten separate studies of diethylcarbamazine (DEC) conducted at the Onchocerciasis Chemotherapeutic Research Centre, Tamale, between 1978 and 1983. Regression models of microfilarial load at different intervals post-treatment are fitted with initial microfilarial load, total dose of DEC, duration of treatment and age of the patient as the independent variables. Appropriate transformations of the variables are chosen by examination of plots of residuals for violations of the assumptions underlying the regression models. A dose response curve for DEC is produced.
Dogba, P K; Komi, B T
We have evaluated the endemicity of the onchocerciasis in two villages of the district of Amou in Togo, Okpahoué et Onglo. We have studied 294 subjects including 136 males and 158 females representing the quarter of the population of the two villages (clinical investigation and exsanguine cutaneous biopsy): 111 persons are parasited by Onchocerca volvulus that means a prevalence rate of 37.7%. We can therefore say that the villages are in a state of "meso-endemicity". We have been able to find nodules by 20 persons among the 111 that give a percentage of 6.8 of the examined persons. Among children of 3 to 9 years old, the prevalence and the average microfilaremia are respectively 8.86 and 3.54%. Among the persons of 50 or older than 50, we found a prevalence rate of 65.95% and an average microfilaremia of 28.37.
Bryceson, A D; Warrell, D A; Pope, H M
Nine Nigerians with severe onchocerciasis who were treated with diethylcarbamazine developed clinical changes, ranging in severity from mild itching to distress, cough, and syncope. Physiological changes (fever, tachypnoea, tachycardia, or hypotension) were seen in eight. In five patients the systolic blood pressure fell by more than 25 mm Hg, and one patient collapsed on attempting to sit up. Circulating eosinophils decreased profoundly in all cases, reaching their lowest levels just before or during the clinical and physiological changes. A fall in serum complement (c3) accompanied the reaction but there was no fall in antibody titre. Diethylcarbamazine probably acts on the parasite's cuticle, thus exposing it to the body's defence mechansims. The reaction coincides with the death of microfilariae, and the accompanying physiological changes may be so severe, even in generally healthy patients, the treatment should perferably be started in hospital.
Taylor, H R; Greene, B M
Twenty men with moderate infection of Onchocerca volvulus were studied in a double-masked, controlled clinical trial to compare the safety and efficacy of oral diethylcarbamazine (DEC) with topical DEC lotion. Visual acuity and colour vision did not alter during the 6 months of observation, although 2 patients receiving DEC lotion and 3 patients receiving oral DEC developed either visual field constriction or optic atrophy. Fluffy corneal opacities were common in both groups. Intraocular microfilariae also appeared in both groups but to a greater extent in those receiving DEC lotion. New chorioretinal changes developed in 4 men receiving lotion and in only 1 receiving tablets. It is concluded that DEC lotion offers no advantage over tablets in the treatment of ocular onchocerciasis and in fact may be associated with more ocular complications than the conventional oral treatment.
Lee, S J; Francis, H L; Awadzi, K; Ottesen, E A; Nutman, T B
To define the changes in antibody response to Onchocerca volvulus antigens after treatment of patients with onchocerciasis, IgG and IgE antibodies were examined quantitatively and qualitatively in 21 patients and 3 control individuals before and sequentially for 14 days after treatment with diethylcarbamazine. The quantitative levels of IgE and IgG responses (both polyclonal and O. volvulus-specific) remained essentially unchanged for all patients, but 9 of the 21 patients showed intensified responses to one or more parasite-specific antigens, and 8 of 21 developed antibodies to previously undetected antigens. There was a significant correlation between the intensities of infection and the development of newly recognized anti-O. volvulus antibodies. These studies demonstrate that O. volvulus-specific IgE and IgG antibody responses are, at least transiently, enhanced by treatment with diethylcarbamazine and that after treatment, parasites possibly release antigens previously hidden from the host's immune response.
Dominguez-Vazquez, A; Taylor, H R; Greene, B M; Ruvalcaba-Macias, A M; Rivas-Alcala, A R; Murphy, R P; Beltran-Hernandez, F
Flubendazole, an injectable benzimidazole drug, was compared with diethylcarbamazine (DEC) in a prospective double-blind study of the treatment of onchocerciasis. Nineteen Mexican men were randomly assigned to receive either flubendazole 750 mg intramuscularly once a week for 5 doses, or DEC 100 mg twice daily for 14 days, and they were then followed up for 12 months. Major systemic side-effects during the first 3 weeks were common in the DEC group but not in the flubendazole group in which there was considerable inflammation at the injection site instead. Ocular complications (limbitis, punctate keratitis, and uveitis) were also common in the DEC group, whereas in the flubendazole group they consisted only of one new punctate opacity at day 4 in one subject. One DEC patient also had several new areas of chorioretinal changes on day 2 but these had disappeared by 2 months. Skin microfilaria counts fell rapidly in the DEC group, but returned to the pretreatment levels. In contrast, skin microfilaria counts in the flubendazole group fell slowly, but by 6 and 12 months were lower than in the DEC group (at 12 months 0.2 vs 7.3 mf/mg, p less than 0.001). In addition, by 6 months none of the flubendazole subjects had intracorneal microfilariae, and only one had microfilariae in the anterior chamber, whereas the numbers of intraocular microfilariae in the DEC group had returned to pretreatment levels. The results suggest that flubendazole is safer and more effective than DEC in the treatment of onchocerciasis.
Limaye, A P; Abrams, J S; Silver, J E; Awadzi, K; Francis, H F; Ottesen, E A; Nutman, T B
To understand the role of the eosinophilopoietic cytokine IL-5 in humans, the posttreatment eosinophilic response in a group of microfilaria (mf)-positive patients with onchocerciasis (n = 10) was examined before and after treatment with diethylcarbamazine (6 mg/kg for 7 d). Sequential blood samples were assessed at 24 and 1 h before treatment (baseline values), then at frequent intervals over the next 14 d. Symptom scores, skin microfilariae (mf), and peripheral blood eosinophil counts were recorded as a function of time after treatment, and serum levels of IL-5 were quantitated by a highly sensitive (sensitivity greater than or equal to 20 pg/ml) monoclonal-based ELISA. Pretreatment eosinophil counts ranged from 240 to 1,186 eosinophils/microliter (geometric mean, 675), and the mf counts from 10 to 218 per mg skin (geometric mean, 79). After an initial decline in the peripheral eosinophil count to 28 +/- 8% of pretreatment levels at 8 h after beginning treatment, the eosinophil counts steadily increased over the next 2 wk, reaching a maximum at 14 d (257 +/- 38% of pretreatment levels). Serum levels of IL-5 rose sharply from pretreatment levels to a peak of 70.5 +/- 11 pg/ml by 24 h after treatment. Serum IL-5 remained elevated over the next 2-3 d and declined toward baseline by approximately 6 d after treatment, at which time the eosinophil levels were steadily increasing. IL-3 and granulocyte macrophage colony-stimulating factor, two other cytokines implicated in eosinophilopoeisis, were not detectable in the serum at any time before or after treatment. The rise in serum IL-5 before the posttreatment eosinophilia seen in this group of patients with onchocerciasis demonstrates a temporal relationship between IL-5 and the subsequent development of eosinophilia and implicates IL-5 as an important mediator of eosinophilia in humans.
Laura Moya Alonso
Full Text Available Background: Onchocerciasis or river blindness is a chronic parasitic disease caused by the filarial nematode Onchocerca Volvulus. It occurs in 38 countries in the world, including Africa, Latin America and the Arabian Peninsula. The infection predominantly causes visual impairment and blindness and skin disease. Objectives: The aim of this project is to review the literature on the psycho-social and economic consequences of onchocerciasis in endemic areas. Economic evaluation studies on onchocerciasis and its control programmes were also reviewed. Methods: Electronic searches of PUBMED and Google were made. In addition, the Cochrane Library and WHO website were searched. Different types of economic analysis were reviewed to quantify the relationship between the programme costs and impacts. Results: Eighty papers were identified from different sources, most of which are quantitative studies or literature reviews, and only two were clinical trials. Onchocerciasis has severe socio-economic and psychological consequences. The stigma associated with the disease may reduce marital prospects among affected individuals, disrupt social relationships and cause loss of self-confidence. Also among agricultural workers onchocerciasis has been associated with increased time away from work and reduced productivity, leading to lower income. Discussion: Most of the papers analysed were cross-sectional studies based on data collection through questionnaires. Although there is an increasing number of published papers about the importance of the psycho-social and economic perspective of onchocerciasis, further research is still necessary to quantify and control its consequences. Conclusion: Onchocerciasis is still a serious problem in poor countries. Infected people face physical disability and social stigma that can dramatically reduce the quality of life and land productivity. Control programmes, though costly, have been very successful and cost
Full Text Available Although the depiction of a child leading a blind man is the most enduring image of onchocerciasis in Africa, research activities have hardly involved children. This paper aims at giving voice to children through drawings and their interpretation. The study was conducted in 2009 in Cameroon, Democratic Republic of Congo (DRC, Nigeria and Uganda. Children aged 6–16 years were asked to draw their perceptions of onchocerciasis and community-directed treatment with ivermectin (CDTI in their communities. A total of 50 drawings were generated. The drawings depicted four main aspects of onchocerciasis: (1 the disease symptoms, (2 the negative consequences of onchocerciasis among children and in the community generally, (3 the ivermectin distribution process, and (4 the benefits or effects of taking ivermectin. Out of the 50 drawings, 30 were on symptoms, 7 on effects of the disease on children, 8 on distribution process, and 5 represented multiple perceptions on symptoms, drug distribution processes, benefits, and effects of treatment. The lack of clarity when treatment with ivermectin can be stopped in endemic areas requires working with children to ensure continued compliance with treatment into the future. Children's drawings should be incorporated into health education interventions.
S.P. Krotneva (Stanimira P.); L.E. Coffeng (Luc); M. Noma (Mounkaila); H.G.M. Zouré (Honorat G.); L. Bakoné (Lalle); U.V. Amazigo (Uche); S.J. de Vlas (Sake); W.A. Stolk (Wilma)
textabstractSince its initiation in 1995, the African Program for Onchocerciasis Control (APOC) has had a substantial impact on the prevalence and burden of onchocerciasis through annual ivermectin mass treatment. Ivermectin is a broad-spectrum anti-parasitic agent that also has an impact on other c
Full Text Available Abstract Background In most endemic parts of the world, onchocerciasis (river blindness control relies, or will soon rely, exclusively on mass treatment with the microfilaricide ivermectin. Worldwide eradication of the parasite by means of this drug is unlikely. Macrofilaricidal drugs are currently being developed for human use. Methods We used ONCHOSIM, a microsimulation mathematical model of the dynamics of onchocerciasis transmission, to explore the potentials of a hypothetical macrofilaricidal drug for the elimination of onchocerciasis under different epidemiological conditions, as characterized by previous intervention strategies, vectorial capacity and levels of coverage. Results With a high vector biting rate and poor coverage, a very effective macrofilaricide would appear to have a substantially higher potential for achieving elimination of the parasite than does ivermectin. Conclusions Macrofilaricides have a substantially higher potential for achieving onchocerciasis elimination than ivermectin, but high coverage levels are still key. When these drugs become available, onchocerciasis elimination strategies should be reconsidered. In view of the impact of control efforts preceding the introduction of macrofilaricides on the success of elimination, it is important to sustain current control efforts.
Duerr, Hans P; Raddatz, Günter; Eichner, Martin
Control of onchocerciasis in Africa is currently based on annual community-directed treatment with ivermectin (CDTI) which has been assumed to be not efficient enough to bring about elimination. However, elimination has recently been reported to have been achieved by CDTI alone in villages of Senegal and Mali, reviving debate on the eradicability of onchocerciasis in Africa. We investigate the eradicability of onchocerciasis by examining threshold shifts and breakpoints predicted by a stochastic transmission model that has been fitted extensively to data. We show that elimination based on CDTI relies on shifting the threshold biting rate to a level that is higher than the annual biting rate. Breakpoints become relevant in the context of when to stop CDTI. In order for the model to predict a good chance for CDTI to eliminate onchocerciasis, facilitating factors such as the macrofilaricidal effect of ivermectin must be assumed. A chart predicting the minimum efficacy of CDTI required for elimination, dependent on the annual biting rate, is provided. Generalisable recommendations into strategies for the elimination of onchocerciasis are derived, particularly referring to the roles of vectors, the residual infection rate under control, and a low-spreader problem originating from patients with low parasite burdens.
Abdul-Ghani, Rashad; Mahdy, Mohammed A K; Beier, John C
Onchocerciasis is a neglected parasitic disease affecting the poorest underserved people in Yemen. A national control programme with goals to eliminate onchocerciasis has yet to be launched due to the current upheaval and social unrest in the country. The disease, locally termed as sowda, is unique in its clinicopathologic pattern, being of the localized, non-blinding, hyperreactive onchocercal skin disease. Although early reports identified endemic foci along seasonal watercourses, there is a need to redefine its epidemiologic patterns as well as health and socioeconomic impacts. Laboratory diagnosis of sowda among Yemeni patients is difficult due to the low load of microfilariae in skin snips and the presence of asymptomatic itching-free microfilaria carriers. Adoption of ivermectin use at three-month intervals as a control strategy has not been evaluated because the drug is mostly used in clinics and distributed to only a few affected communities. This paper addresses key aspects of onchocerciasis in Yemen and highlights the need for screening at-risk populations using highly sensitive techniques and mapping the distributions of the parasite in human and vector populations of blackflies. The new research should be integrated with the launch of a national onchocerciasis control programme to achieve onchocerciasis elimination.
Connor, D H; Gibson, D W; Neafie, R C; Merighi, B; Buck, A A
Sowda is an unusual form of onchocerciasis in Yemenites that differs from African onchocerciasis. Clinical and pathological studies were performed on 18 patients in Yemen Arab Republic (North Yemen). Biopsies of skin and lymph nodes were taken, and then processed at the Armed Forces Institute of Pathology, Washington, D.C. The most striking clinical features were swollen, darkened, pruritic, papular skin changes that were usually limited to one leg, more rarely to one arm, and large soft regional lymph nodes. Dermal changes were deeper and more diffuse than in African onchocerciasis, with many large fibroblasts and plasma cells. Microfilariae of Onchocerca volvulus were much rarer in skin from Yemenites with sowda. When patients were treated with diethylcarbamazine, the dermatitis became suddenly worse as the microfilariae degenerated and provoked acute inflammation. The dermatitis decreased after several days of treatment. Enlarged lymph nodes from sowda have shown follicular hyperplasia, in contrast to follicular atrophy and perivascular fibrosis that are characteristic of lymph nodes from cases of African onchocerciasis. Cell-mediated and humoral immunity may be more active in sowda than in African onchocerciasis.
Fendt, J; Hamm, D M; Banla, M; Schulz-Key, H; Wolf, H; Helling-Giese, G; Heuschkel, C; Soboslay, P T
Ivermectin treatment will effectively diminish microfilariae (Mf) of Onchocerca volvulus in the skin of patients, but therapy is associated with adverse host inflammatory responses. To investigate the association of proinflammatory chemokines with the intensity of infection and clinical adverse reactions, chemokine serum levels were measured in patients following ivermectin treatment (100 microg/kg, 150 microg/kg or 200 microg/kg) or placebo. The density of O. volvulus Mf per mg skin decreased by 85%, 97%, 97% and 90% at day 3, at month 3, month 6 and at 1 year post-ivermectin. The cutaneous T cell-attracting chemokine (CTACK/CCL27) was found highly elevated in onchocerciasis patients compared to infection-free European controls (P = 0.0004) and it did not change following ivermectin or placebo to 1 year post-therapy. The chemokine RANTES/CCL5 (regulated on activated and normally T cell-expressed) was similarly high in onchocerciasis patients and infection-free European controls; the RANTES/CCL5 levels did not change following treatment until 6 months post-therapy but were slightly elevated at 1 year post-therapy (P ivermectin (P ivermectin treatment, but following clearance of microfilariae of O. volvulus their levels increased from 6 months post-therapy onwards (for both at 12 months post-therapy, P dose of ivermectin or with the serum levels of MIP-1alpha/CCL3, MIP-1beta/CCL4, TARC/CCL17, MDC/CCL22 and CTACK/CCL27. Our observations suggest that following ivermectin, macrophages as well as memory Th2-type lymphocytes and B cells, attracted and activated by MDC/CCL22, TARC/CCL17 and CTACK/CCL27, may contribute to dermal immune responses and O. volvulus Mf killing and clearance. The transient changes of TARC/CCL17 and MDC/CCL22 were not associated with clinical adverse responses, and the later rise of MIP-1alpha/CCL3 and MIP-1beta/CCL4 showed a reactivation of Type 1 immune responses associated with persistent low levels of O. volvulus microfilariae and an expiring
Full Text Available Ed W Cupp1, Charles D Mackenzie2, Thomas R Unnasch31Department of Entomology and Plant Pathology, Auburn University, Auburn, AL, USA; 2Department of Pathobiology, Michigan State University, East Lansing, MI, USA; 3Department of Global Health, University of South Florida, Tampa, FL, USAAbstract: Ivermectin (registered for human use as Mectizan® was donated by Merck & Co Inc in 1987 for the treatment and control of human onchocerciasis ("river blindness". This philanthropic gesture has had a remarkable effect in reducing the incidence and prevalence of this serious ocular and dermatological disease, while changing health system support for millions of people worldwide. Over 800 million doses have been given to more than 80 million people for onchocerciasis during the past 23 years. As a result, onchocerciasis has been significantly reduced in more than 25 countries, transmission has been interrupted in foci in at least 10 countries, and the disease is no longer seen in children in many formerly endemic foci. Recent communications have suggested that the drug's efficacy as the major therapeutic agent for these control and elimination programs may be threatened, but alternative interpretations for suboptimal response/resistance suggest otherwise. Current research needs and control methods by which the public health community in endemic countries may respond to resistance, should it occur in their area, are discussed, along with the continuing importance of this anthelmintic as the mainstay in onchocerciasis control programs.Keywords: Ivermectin, Onchocerca volvulus, river blindness, resistance, African Programme for Onchocerciasis Control, Onchocerciasis Elimination Program for the Americas
Amazigo, U; Noma, M; Boatin, B A; Etya'alé, D E; Sékétéli, A; Dadzie, K Y
The efficiency of on-going delivery systems and cost recovery in Mectizan (ivermectin, MSD) treatment for onchocerciasis are reviewed. The search is on for an effective system of Mectizan delivery, involving drug procurement, delivery from port to districts and distribution to eligible persons, which can be sustained by the endemic countries for many years. The mechanisms for procuring and clearing the drug at the ports, and the drug's integration into the existing delivery systems of each national health service, need to be improved. Although large-scale treatments by mobile teams or community-based methods evidently achieve high and satisfactory rates of coverage, they also incur high recurrent costs which have to be covered by external partners and are not sustainable by national health services. Cost-sharing is considered an important factor in a sustainable delivery system and community-directed treatment, in which the community shares the cost and ownership of local distribution and is empowered to design and implement it, is likely to be more cost-effective and sustainable.
Herzog-Neto, Guilherme; Jaegger, Karen; do Nascimento, Erika S.; Marchon-Silva, Verônica; Banic, Dalma M.; Maia-Herzog, Marilza
To determine the influence of onchocercal eye disease on the intraocular pressure of the Yanomami Tribe Aratha-ú of Roraima State, Brazil, considered endemic for onchocerciasis, a total of 86 patients were submitted to an ophthalmologic exam that included external examination, slit lamp examination, intraocular pressure measurement, and a fundus ophthalmoscope examination. A high prevalence of onchocerciasis-related eye lesions was encountered in 68.6% of the patients. Punctate keratitis and microfilariae in the anterior chamber were found in ∼28%. The mean of intraocular eye pressure found was 10.47 mm of Hg. PMID:24297812
L.E. Coffeng (Luc); S.D.S. Pion (Sébastien); S. O'Hanlon (Simon); S. Cousens (Simon); A.O. Abiose (Adenike); P.U. Fischer (Peter); J.H.F. Remme (Jan); K.Y. Dadzie (Yankum); M.E. Murdoch (Michele); S.J. de Vlas (Sake); M-G. Basáñez (María-Gloria); W.A. Stolk (Wilma); M. Boussinesq (Michel)
markdownabstract*Background*: The prospect of eliminating onchocerciasis from Africa by mass treatment with ivermectin has been rejuvenated following recent successes in foci in Mali, Nigeria and Senegal. Elimination prospects depend strongly on local transmission conditions and therefore on pre-con
W.A. Stolk (Wilma); M. Walker (Martin); L.E. Coffeng (Luc); M-G. Basáñez (María-Gloria); S.J. de Vlas (Sake)
textabstractBackground: The World Health Organization (WHO) has set ambitious targets for the elimination of onchocerciasis by 2020-2025 through mass ivermectin treatment. Two different mathematical models have assessed the feasibility of reaching this goal for different settings and treatment scena
Luz, Sérgio Luiz Bessa; Crainey, James Lee; Shelley, Anthony John; Rubio, Miguel
In a recent issue of Memórias do Instituto Oswaldo Cruz, published in Rio de Janeiro in February 2014 (109: 87-92), Adami et al. have published a survey reporting Mansonella parasite prevalence in the Amazon Region. This report makes a useful contribution to the existing knowledge of filarial parasite distribution within the Amazon area, parasite prevalence rates in relation to age and occupation and provides observations on the possible clinical impact of Mansonella ozzardi. Their publication also provides an account of what appears to be a novel ELISA that has recently been used in the Simuliidae and Onchocerciasis Laboratory of the Oswaldo Cruz Institute, Rio de Janeiro, Brazil. We are concerned that the publication of this ELISA may have created an excessively positive impression of the effectiveness of the onchocerciasis recrudescence serological surveillance tools that are presently available for use in the Amazonia onchocerciasis focus. In this letter we have, thus, sought to highlight some of the limitations of this ELISA and suggest how continuing insecurities concerning the detection of antibodies to Onchocerca volvulus within the Amazonia onchocerciasis focus might be minimised.
Sérgio Luiz Bessa Luz
Full Text Available In a recent issue of Memórias do Instituto Oswaldo Cruz, published in Rio de Janeiro in February 2014 (109: 87-92, Adami et al. have published a survey reporting Mansonella parasite prevalence in the Amazon Region. This report makes a useful contribution to the existing knowledge of filarial parasite distribution within the Amazon area, parasite prevalence rates in relation to age and occupation and provides observations on the possible clinical impact of Mansonella ozzardi. Their publication also provides an account of what appears to be a novel ELISA that has recently been used in the Simuliidae and Onchocerciasis Laboratory of the Oswaldo Cruz Institute, Rio de Janeiro, Brazil. We are concerned that the publication of this ELISA may have created an excessively positive impression of the effectiveness of the onchocerciasis recrudescence serological surveillance tools that are presently available for use in the Amazonia onchocerciasis focus. In this letter we have, thus, sought to highlight some of the limitations of this ELISA and suggest how continuing insecurities concerning the detection of antibodies to Onchocerca volvulus within the Amazonia onchocerciasis focus might be minimised.
Use of the recombinant Onchocerca volvulus protein Ov20/OvS1 for the immunodiagnostic differentiation between onchocerciasis and mansonelliasis and for the characterization of hyperreactive onchocerciasis (sowda)
Mpagi, J. L; Büttner, D. W; Tischendorf, F. W; Erttmann, K. D; Brattig, N. W
... of Onchocerca volvulus infection (sowda). The specificity of the IgG4 Western blot was 98% for the differentiation between persons with onchocerciasis and Mansonella microfilariae (mf) carriers (125 persons with M...
Makenga Bof, J-C; Maketa, V; Bakajika, D K; Ntumba, F; Mpunga, D; Murdoch, M E; Hopkins, A; Noma, M M; Zouré, H; Tekle, A H; Katabarwa, M N; Lutumba, P
To evaluate onchocerciasis control activities in the Democratic Republic of Congo (DRC) in the first 12 years of community-directed treatment with ivermectin (CDTI). Data from the National Programme for Onchocerciasis (NPO) provided by the National Onchocerciasis Task Force (NOTF) through the annual reports of the 21 CDTI projects for the years 2001-2012 were reviewed retrospectively. A hypothetical-inputs-process-outputs-outcomes table was constructed. Community-directed treatment with ivermectin expanded from 1968 communities in 2001 to 39 100 communities by 2012 while the number of community-directed distributors (CDD) and health workers (HW) multiplied. By 2012, there were ratios of 1 CDD per 262 persons and 1 HW per 2318 persons at risk. More than 80% of the funding came from the fiduciary funds of the African Programme for Onchocerciasis Control. The cost of treatment per person treated fell from US$ 1.1 in 2001 to US$ 0.1 in 2012. The therapeutic coverage increased from 2.7% (2001) to 74.2% (2012); the geographical coverage, from 4.7% (2001) to 93.9% (2012). Geographical coverage fell in 2005 due to deaths in loiasis co-endemic areas, and the therapeutic coverage fell in 2008 due to insecurity. Challenges to CDTI in DRC have been serious adverse reactions to ivermectin in loiasis co-endemic areas and political conflict. Targets for personnel or therapeutic and geographical coverages were not met. Longer term funding and renewed efforts are required to achieve control and elimination of onchocerciasis in DRC. © 2014 John Wiley & Sons Ltd.
Hugo C Turner
Full Text Available BACKGROUND: Recent studies in Mali, Nigeria, and Senegal have indicated that annual (or biannual ivermectin distribution may lead to local elimination of human onchocerciasis in certain African foci. Modelling-based projections have been used to estimate the required duration of ivermectin distribution to reach elimination. A crucial assumption has been that microfilarial production by Onchocerca volvulus is reduced irreversibly by 30-35% with each (annual ivermectin round. However, other modelling-based analyses suggest that ivermectin may not have such a cumulative effect. Uncertainty in this (biological and other (programmatic assumptions would affect projected outcomes of long-term ivermectin treatment. METHODOLOGY/PRINCIPAL FINDINGS: We modify a deterministic age- and sex-structured onchocerciasis transmission model, parameterised for savannah O. volvulus-Simulium damnosum, to explore the impact of assumptions regarding the effect of ivermectin on worm fertility and the patterns of treatment coverage compliance, and frequency on projections of parasitological outcomes due to long-term, mass ivermectin administration in hyperendemic areas. The projected impact of ivermectin distribution on onchocerciasis and the benefits of switching from annual to biannual distribution are strongly dependent on assumptions regarding the drug's effect on worm fertility and on treatment compliance. If ivermectin does not have a cumulative impact on microfilarial production, elimination of onchocerciasis in hyperendemic areas may not be feasible with annual ivermectin distribution. CONCLUSIONS/SIGNIFICANCE: There is substantial (biological and programmatic uncertainty surrounding modelling projections of onchocerciasis elimination. These uncertainties need to be acknowledged for mathematical models to inform control policy reliably. Further research is needed to elucidate the effect of ivermectin on O. volvulus reproductive biology and quantify the patterns of
Luc E Coffeng
Full Text Available BACKGROUND: Onchocerciasis causes a considerable disease burden in Africa, mainly through skin and eye disease. Since 1995, the African Programme for Onchocerciasis Control (APOC has coordinated annual mass treatment with ivermectin in 16 countries. In this study, we estimate the health impact of APOC and the associated costs from a program perspective up to 2010 and provide expected trends up to 2015. METHODS AND FINDINGS: With data on pre-control prevalence of infection and population coverage of mass treatment, we simulated trends in infection, blindness, visual impairment, and severe itch using the micro-simulation model ONCHOSIM, and estimated disability-adjusted life years (DALYs lost due to onchocerciasis. We assessed financial costs for APOC, beneficiary governments, and non-governmental development organizations, excluding cost of donated drugs. We estimated that between 1995 and 2010, mass treatment with ivermectin averted 8.2 million DALYs due to onchocerciasis in APOC areas, at a nominal cost of about US$257 million. We expect that APOC will avert another 9.2 million DALYs between 2011 and 2015, at a nominal cost of US$221 million. CONCLUSIONS: Our simulations suggest that APOC has had a remarkable impact on population health in Africa between 1995 and 2010. This health impact is predicted to double during the subsequent five years of the program, through to 2015. APOC is a highly cost-effective public health program. Given the anticipated elimination of onchocerciasis from some APOC areas, we expect even more health gains and a more favorable cost-effectiveness of mass treatment with ivermectin in the near future.
Henri Lucien Fouamno Kamga
Full Text Available <0.001. The greatest rate of infection was found among farmers (2.5% followed by students (0.7% and businessmen (0.25%. CONCLUSION: This study shows that the study area is now hypo-endemic for onchocerciasis, following 6 years of continuous treatment with ivermectin. Careful monitoring of onchocerciasis should however be continued to avoid that the area returns to its initial hyper endemicity.
Turner, Hugo C.; Churcher, Thomas S.; Martin Walker; Osei-Atweneboana, Mike Y.; Prichard, Roger K.; María-Gloria Basáñez
BACKGROUND: Recent studies in Mali, Nigeria, and Senegal have indicated that annual (or biannual) ivermectin distribution may lead to local elimination of human onchocerciasis in certain African foci. Modelling-based projections have been used to estimate the required duration of ivermectin distribution to reach elimination. A crucial assumption has been that microfilarial production by Onchocerca volvulus is reduced irreversibly by 30-35% with each (annual) ivermectin round. However, other m...
Krüger, A; Kalinga, A K; Post, R J; Maegga, B T A
During a distribution survey of Simulium damnosum s.l. around the Tukuyu onchocerciasis focus at the northern tip of Lake Malawi/Nyasa (Tanzania), we discovered two new cytoforms of the S. damnosum complex in onchocerciasis-free areas. The Nyika form is related to Simulium thyolense, a vector of onchocerciasis, and can be identified by the new inversion 3L-L on the long arm of chromosome 3. It was found breeding in five rivers in northern Malawi and neighbouring Tanzania and is assumed to be zoophilic. The Njombe form represents a member of the Sanje group of the complex and is characterized by the new diagnostic inversion 2L-35 on chromosome 2. So far, it is only known from around Njombe town in southern Tanzania, where it breeds at remarkably high altitudes. Anthropophily for the Njombe form is well known. The medical importance and systematic position of the new forms within the S. damnosum complex are discussed.
Turner, P F; Rockett, K A; Ottesen, E A; Francis, H; Awadzi, K; Clark, I A
Adverse reactions following treatment of onchocerciasis and bancroftian filariasis are common and frequently severe. They are generally caused not by direct drug toxicity but by host inflammatory responses to dying microfilariae. To define the responsible mechanism, serial blood levels of interleukin-6 (IL-6) and tumor necrosis factor (TNF) were studied in 15 microfilaria-positive patients (10 with bancroftian filariasis, 5 with onchocerciasis) and 4 microfilaria-negative persons after diethylcarbamazine treatment. Elevations in IL-6 correlated with the occurrence and severity of clinical symptoms after treatment; for the onchocerciasis patients IL-6 levels directly reflected pretreatment intensity of infection. Serum TNF levels also rose but did not correlate directly with infection intensity or reaction severity. Microfilaria-negative controls remained asymptomatic with no significant rise in either cytokine. These findings suggest an etiologic role for systemically elevated cytokines in the inflammatory reactions developing after treatment of filarial infections in humans.
Bird, A C; el-Sheikh, H; Anderson, J; Fuglsang, H
Eighteen patients, moderately to heavily infected with onchocerciasis, were treated with a standard course of diethylcarbamazine citrate (DEC-C). In addition to the well recognised systemic reactions to treatment, the following ocular changes occurred during therapy: (1) Transient pigment epithelial lesions were detected in 7 patients by fluorescein angiography. (2) Optic disc leakage, as shown by fluorescein angiography, developed in 9 patients, and increase of pre-existing leakage was demonstrated in 3 further patients. (3) Visual field loss was documented in 5 patients. These observations have grave implications for DEC-C therapy in onchocerciasis. They emphasise the need for great caution in its use in the treatment of onchocerciasis in heavily infected patients and for close supervision of ocular function during therapy.
Awadzi, K; Dadzie, K Y; Schulz-Key, H; Gilles, H M; Fulford, A J; Aziz, M A
Fifty-nine onchocerciasis patients with ocular involvement were randomly assigned to receive either 12 mg of ivermectin in a single dose or 1300 mg of diethylcarbamazine over eight days or matching placebo capsules. Detailed standardized follow-up examination was carried out for one year. Both ivermectin and diethylcarbamazine rapidly reduced skin microfilarial counts to a similar extent over six months, after which counts increased significantly more with diethylcarbamazine. Diethylcarbamazine rapidly eliminated microfilariae from the eye, while ivermectin did so over six months. Reactions to treatment were more severe with diethylcarbamazine, which also produced clinical ocular deficiency in two patients. Ivermectin produced intra-uterine sequestration and degeneration of microfilariae in adult worms, which may account for its ability to produce prolonged suppression of skin microfilariae. Ivermectin proved superior to diethylcarbamazine in safety, tolerance and efficacy, but further work is needed to assess fully its effects in patients with heavy intraocular microfilarial loads.
Luc E Coffeng
Full Text Available BACKGROUND: The prospect of eliminating onchocerciasis from Africa by mass treatment with ivermectin has been rejuvenated following recent successes in foci in Mali, Nigeria and Senegal. Elimination prospects depend strongly on local transmission conditions and therefore on pre-control infection levels. Pre-control infection levels in Africa have been mapped largely by means of nodule palpation of adult males, a relatively crude method for detecting infection. We investigated how informative pre-control nodule prevalence data are for estimating the pre-control prevalence of microfilariae (mf in the skin and discuss implications for assessing elimination prospects. METHODS AND FINDINGS: We analyzed published data on pre-control nodule prevalence in males aged ≥ 20 years and mf prevalence in the population aged ≥ 5 years from 148 African villages. A meta-analysis was performed by means of Bayesian hierarchical multivariate logistic regression, accounting for measurement error in mf and nodule prevalence, bioclimatic zones, and other geographical variation. There was a strong positive correlation between nodule prevalence in adult males and mf prevalence in the general population. In the forest-savanna mosaic area, the pattern in nodule and mf prevalence differed significantly from that in the savanna or forest areas. SIGNIFICANCE: We provide a tool to convert pre-control nodule prevalence in adult males to mf prevalence in the general population, allowing historical data to be interpreted in terms of elimination prospects and disease burden of onchocerciasis. Furthermore, we identified significant geographical variation in mf prevalence and nodule prevalence patterns warranting further investigation of geographical differences in transmission patterns of onchocerciasis.
Ryan M Young
Full Text Available Entomological indicators are considered key metrics to document the interruption of transmission of Onchocerca volvulus, the etiological agent of human onchocerciasis. Human landing collection is the standard employed for collection of the vectors for this parasite. Recent studies reported the development of traps that have the potential for replacing humans for surveillance of O. volvulus in the vector population. However, the key chemical components of human odor that are attractive to vector black flies have not been identified.Human sweat compounds were analyzed using GC-MS analysis and compounds common to three individuals identified. These common compounds, with others previously identified as attractive to other hematophagous arthropods were evaluated for their ability to stimulate and attract the major onchocerciasis vectors in Africa (Simulium damnosum sensu lato and Latin America (Simulium ochraceum s. l. using electroantennography and a Y tube binary choice assay. Medium chain length carboxylic acids and aldehydes were neurostimulatory for S. damnosum s.l. while S. ochraceum s.l. was stimulated by short chain aliphatic alcohols and aldehydes. Both species were attracted to ammonium bicarbonate and acetophenone. The compounds were shown to be attractive to the relevant vector species in field studies, when incorporated into a formulation that permitted a continuous release of the compound over time and used in concert with previously developed trap platforms.The identification of compounds attractive to the major vectors of O. volvulus will permit the development of optimized traps. Such traps may replace the use of human vector collectors for monitoring the effectiveness of onchocerciasis elimination programs and could find use as a contributing component in an integrated vector control/drug program aimed at eliminating river blindness in Africa.
Full Text Available Background: This study was carried out in Opi-Agu a tropical semi-urban autonomous community comprising of three villages in Enugu State, Nigeria, between the months of April and June 2010. It was designed to determine the prevalence of Onchocerca volvulus infection and assess the perception of the disease among the inhabitants of this community.Methods: A total number of 305 individuals comprising of 148 males and 157 females were examined for various manifestations of onchocerciasis symptoms using rapid epidemiological assessment (REA method.Results: Out of this number, 119 (39.02% individuals were infected. Prevalence of infection among age groups and villages varied. Age group 41 yr and above had the highest (31.00% prevalence, while among the villages, Ogbozalla village ranked higher (45.71% than the other villages. Overall the prevalence of infection among the sexes revealed that males were more infected (43.24% than the females (35.03%. Lichenified onchodermatitis (LOD was the most prevalent (35.29% onchocerciasis symptom among others identified in the area, while leopard skin (LS had the lowest (20.17% occurrence and blindness (0.00% which is the most devastating effect of O. volvulus infection was not observed. Questionnaire responses from 410 individuals revealed that 34.8% respondent from Idi village and 28.1% from Ibeku village believed that O. volvulus infection occurs through poor personal hygiene. Bite of blackfly ranked least (10.6% among the respondent’s knowledge of the causes of onchocerciasis in Opi-Agu community.Conclusion: Opi-Agu community members had poor knowledge of onchocerciasis, the vector and of its etiologic organism. There is need for integration of community health education with mass chemotherapy
Young, Ryan M.; Burkett-Cadena, Nathan D.; McGaha, Tommy W.; Rodriguez-Perez, Mario A.; Toé, Laurent D.; Adeleke, Monsuru A.; Sanfo, Moussa; Soungalo, Traore; Katholi, Charles R.; Noblet, Raymond; Fadamiro, Henry; Torres-Estrada, Jose L.; Salinas-Carmona, Mario C.; Baker, Bill; Unnasch, Thomas R.; Cupp, Eddie W.
Background Entomological indicators are considered key metrics to document the interruption of transmission of Onchocerca volvulus, the etiological agent of human onchocerciasis. Human landing collection is the standard employed for collection of the vectors for this parasite. Recent studies reported the development of traps that have the potential for replacing humans for surveillance of O. volvulus in the vector population. However, the key chemical components of human odor that are attractive to vector black flies have not been identified. Methodology/Principal Findings Human sweat compounds were analyzed using GC-MS analysis and compounds common to three individuals identified. These common compounds, with others previously identified as attractive to other hematophagous arthropods were evaluated for their ability to stimulate and attract the major onchocerciasis vectors in Africa (Simulium damnosum sensu lato) and Latin America (Simulium ochraceum s. l.) using electroantennography and a Y tube binary choice assay. Medium chain length carboxylic acids and aldehydes were neurostimulatory for S. damnosum s.l. while S. ochraceum s.l. was stimulated by short chain aliphatic alcohols and aldehydes. Both species were attracted to ammonium bicarbonate and acetophenone. The compounds were shown to be attractive to the relevant vector species in field studies, when incorporated into a formulation that permitted a continuous release of the compound over time and used in concert with previously developed trap platforms. Conclusions/Significance The identification of compounds attractive to the major vectors of O. volvulus will permit the development of optimized traps. Such traps may replace the use of human vector collectors for monitoring the effectiveness of onchocerciasis elimination programs and could find use as a contributing component in an integrated vector control/drug program aimed at eliminating river blindness in Africa. PMID:25569240
Ezzedine, Khaled; Malvy, Denis; Dhaussy, Ines; Steels, Emmanuelle; Castelein, Carine; De Dobbeler, Gilbert; Heenen, Michel
Travelers to West Central Africa are at risk for infection with Onchocerca volvulus. We describe the case of an adventurous traveler who became infected with O volvulus after a 10-day stay in rural Cameroon. Two years after his return, he was diagnosed with a 3-month history of limb swelling with pruritus and fixed edema of the right arm. He was successfully treated by a single dose of ivermectin, with an additional treatment with doxycycline. The patient was followed-up during 1 year after therapy without relapse. Such travelers experiencing unusual dermatitis syndromes should prompt evaluation for onchocerciasis.
Taylor, H R; Greene, B M; Langham, M E
In a double-blind controlled clinical trial comparing the safety and efficacy of oral diethylcarbamazine citrate (DEC) with topical DEC for the treatment of onchocerciasis twenty men with moderate skin-snip microfilarial counts received daily therapy for 1 week, then weekly therapy for the rest of 6 months. The number of microfilariae per skin snip dropped quickly to 2% of initial levels and remained at low levels in those receiving oral DEC, and to 20% of initial levels in patients treated with DEC lotion. Side-effects in both groups included lymphadenopathy, fever, pruritus, rash, proteinuria, and chorioretinitis; they were commoner with topical DEC.
Full Text Available Onchocerciasis or river blindness constitutes a major burden to households especially in resource-poor settings, causing a significant reduction in household productivity. There has been renewed interest from policy makers to reduce the burden of Neglected Tropical Diseases (NTDs such as onchocerciasis on individuals and households. This paper provides new information on the patient's perceptions of onchocerciasis and its economic burden on households in South-eastern Nigeria. The information will be useful to health providers and policy makers for evidence-informed resource allocation decisions.Information was generated from a cross-sectional household survey conducted in Achi community, Oji River Local Government Area (LGA of Enugu State, Southeast Nigeria. A pre-tested interviewer-administered questionnaire was used to collect data. A total of 747 households were visited randomly and data were collected using pre-tested interviewer administered questionnaire from 370 respondents. The respondents' knowledge of the cause of symptoms of the disease, costs incurred for seeking treatment and productivity losses were elicited. Data were analyzed using tabulations and inferential statistics. A socio-economic status (SES index was used to disaggregate some key variables by SES quintiles for equity analysis.Many people had more than one type of manifestation of onchocerciasis. However, more than half of the respondents (57% had no knowledge of the cause of their symptoms. Male respondents had significantly more knowledge of the cause of symptoms than females (P = 0.04 but knowledge did not differ across SES (P = 0.82. The average monthly treatment cost per respondent was US$ 14.0. Drug cost (US$10 made up about 72% of total treatment cost. The per capita productivity loss among patients was US$16 and it was higher in the poorest (Q1 (US$20 and the third SES quintiles (Q3 (US$21. The average monthly productivity loss among caregivers was US$3
Rivas-Alcalá, A R; Greene, B M; Taylor, H R; Domíguez-Vázquez, A; Ruvalcaba-Macías, A M; Lugo-Pfeiffer, C; Mackenzie, C D; Beltrán, F
Four drug regimens for treating onchocerciasis were compared in a double-blind study in persons from an endemic area in southern Mexico. 40 men were randomly assigned to receive either diethylcarbamazine (DEC) (200 mg/day), mebendazole (2 g/day), levamisole (150 mg per week), or mebendazole plus levamisole. DEC produced the most rapid fall in skin microfilaria counts, but by 6 months the two groups receiving mebendazole showed similar or slightly greater reductions. Despite the administration of corticosteroids to persons receiving DEC, more systemic side-effects were seen in this group. Ocular complications were also commoner and more severe in those receiving DEC. The reduction in the number of intraocular microfilariae at 6 months was similar to those receiving DEC and mebendazole, alone or in combination with levamisole. Levamisole alone had no significant effect on microfilaria counts. Examination of adult worms in nodules excised at 2 months showed changes suggestive of an interruption of embryogenesis in those persons receiving the mebendazole-containing regimens only. The findings suggest that mebendazole may be a useful alternative to DEC in the treatment of onchocerciasis.
RODGER, F C
The records of 2000 blind or partially blind persons in the onchocerciasis areas of West Africa provided the background information for this report.The author has grouped his material in three sections. The first of these deals with diagnostic methods, and contains the results of skin and conjunctival biopsies, as well as a description of onchocercomas and an estimate of the life-span of Onchocerca adults.Next, the pathogenesis of ocular lesions is discussed in the light of evidence obtained from a series of animal experiments designed to test two theories-namely, the existence of an allergic state and damage by toxins.In the last section, which is devoted to clinical observations, the author demonstrates the existence of a relationship between the posterior segmental lesion and vitamin A deficiency, and shows that punctate corneal opacities result more often from certain virus diseases and malaria than from onchocerciasis. A description follows of various degenerations due to a local nutritional disorder combined with vitamin A deficiency in onchocercal limbitis and anterior uveitis.
Vázquez Castellanos, J L
Due to the social and ecological changes that have taken place in the region of Soconusco, Chiapas, Mexico, the coffee tree growth economy (established in the latter part of the last century) has been an important factor in the transmission of onchocerciasis. The optimum ecological conditions for the growth of the coffee tree coincide with those of the disease's growth rate vector; the mobilization of migrant workers for the cultivation and gathering of coffee beans, plus changes in the natural environment, are elements which explain the disease's distribution in the different regions. The origin of the disease in Chiapas may be due to the migration of coffee plantation workers from Guatemala in search of land in which to settle. Social changes occurring after the Agrarian Distribution (land distributions that occurred in 1918 and 1940) caused an intensification and modernization in the areas of cultivation which in turn caused a decline in the disease's growth rate vector. This, together with standard of living improvements and control measures against the disease, explain why the problem in these regions has decreased considerably. The use of ivermectin as a new therapy paves the way for better disease control in the future. Nevertheless, in the smaller locations occupied by middle and poor class farmers, where coffee bean cultivation is just commencing and still in a rudimentary form, onchocerciasis and other diseases continue to present serious health problems.
A. J. Shelley
Full Text Available Factors that affect the propensity of a simuliid species to act as a host to Onchocerca volvulus and to naturally transmit this filarial worm in nature are discussed. Presence or absence of a cibarial armature is believed to be a major factor that has been previously overlooked and this is considered in relation to the choice of control methods currently advocated for onchocerciasis. The current epidemiological studies, transmission dynamics and relevant control measures are discussed for each onchocerciasis focus in Latin America.Neste trabalho são discutidos os fatores que interferem na suscetibilidade de espécies de simulídeos atuarem como hospedeiros do Onchocerca volvulus e de transmitir a filária em condições naturais. Acredita-se que a presença ou não da armadura do cibário pode ser um fator central, que anteriormente foi subestimado. Este aspecto é discutido em relação às opções em voga de métodos de controle na oncocercose. São também discutidos os estudos epidemiológicos correntes, a dinâmica de transmissão e principais medidas de controle para cada foco de oncocercose na América Latina.
Goa, K L; McTavish, D; Clissold, S P
Ivermectin, a derivative of avermectin B, is an orally effective microfilaricidal agent. It is the current drug of choice for treating patients infected with the nematode Onchocerca volvulus, which is a major cause of blindness in inhabitants of some tropical areas. Ivermectin is administered orally as a single dose of 150 micrograms/kg given annually. Skin and ocular microfilarial counts are dramatically reduced after the first dose, with some evidence for a resulting decrease in transmission of infection by the blackfly vector. With the exception of rare serious reactions such as severe systemic postural hypotension, ivermectin is generally well tolerated. The drug has the clear advantages of ease of administration and better tolerability compared with diethylcarbamazine and suramin, agents previously used to treat onchocerciasis. Thus, ivermectin is suitable for inclusion in mass treatment programmes and is the best therapeutic option presently available to combat onchocerciasis. As such it provides hope for many thousands of people at risk of becoming blind, and represents a major contribution to tropical medicine.
Lariviere, M; Vingtain, P; Aziz, M; Beauvais, B; Weimann, D; Derouin, F; Ginoux, J; Schulz-Key, H; Gaxotte, P; Basset, D
In a randomised double-blind study, ivermectin was compared with diethylcarbamazine (DEC) and placebo in the treatment of onchocerciasis in 30 male patients from Mali with moderate to heavy Onchocerca volvulus infections and ocular involvement. 10 patients received a single oral dose of ivermectin, 12 mg, 10 received DEC daily for eight days (total dose 1.3 g), and 10 received matching placebo. Patients were examined periodically for twelve months. Punctate keratitis disappeared in 6 of 7 ivermectin patients but increased in DEC patients. Numbers of O volvulus microfilariae (mf) in the anterior chamber decreased slowly and eventually disappeared in most ivermectin patients during the six months following treatment; anterior chamber mf disappeared more rapidly in some patients after DEC, but reappeared within six months of stopping treatment. Both ivermectin and DEC caused a prompt decrease in mean skin mf density; density then increased in both groups over the twelve month observation period, reaching 9% of pretreatment values in ivermectin patients and 45% in the DEC group. Analysis of adult O volvulus from nodules excised at three and twelve months post treatment showed no effect of either drug on viability; however, there was evidence of degeneration of intra-uterine developing mf in the ivermectin group. Side-effects were less frequent and less severe in ivermectin patients than in DEC patients. Ivermectin as a single oral dose appears to be a more effective microfilaricidal drug than DEC in onchocerciasis.
Chemotherapy against onchocerciasis and lymphatic filariasis has been discussed mainly within the framework of mass drug administration with diethylcarbamazine, ivermectin and albendazole. Although strong reductions in infection prevalence were achieved, the regimes for these drugs do not fully cover needs of individual patients who seek treatment because of symptoms. Chemotherapy against filarial Wolbachia endosymbionts with doxycycline showed higher antiparasitic efficacy in onchocerciasis and lymphatic filariasis and also improved disease. This review details the recent indications for this new treatment, focussing on regimes for individual drug administration. A regimen of 6-week/100 mg doxycycline per day sterilized adult female Onchocerca volvulus. Two hundred milligrams doxycycline per day for 4 or 6 weeks revealed 50 and 60% macrofilaricidal effects, respectively. Reduction of 80-90% of adult worms was observed in bancroftian filariasis with 200 mg/day doxycycline for 4 or 6 weeks. The latter regimen showed reduction of lymph vessel dilation and of hydrocele. Lymphoedema progression was halted and reversed in early stages. Different options for antiwolbachial individual drug administration are summarized here. With improving health systems in endemic countries, individuals will demand best-possible treatment and accelerate a shift from mass drug administration-only approaches to integrated approaches combining both mass drug administration and individual drug administration. Treatment may be further improved by new antibiotics detected in high-throughput settings.
Jones, B R; Anderson, J; Fuglsang, H
...% to patients with ocular onchocerciasis. Migration of microfilariae into the cornea, followed by their straightening and disintegration, was observed with delivery rates as low as 0.1 microgram/hour...
Philip J. Cooper; Lawrence B. Schwartz; Anne-Marie Irani; Kwablah Awadzi; Ronald H. Guderian; Thomas B. Nutman
To investigate the role of mast cells in treatment-associated adverse reactions in patients with onchocerciasis, changes in plasma tryptase levels and skin mast cell counts were examined in 2 groups...
Full Text Available Abstract Background Although ivermectin is distributed free of charge through the African Programme for Onchocerciasis Control (APOC, not all eligible individuals within communities receive the annual treatment. This poses a serious threat to efforts aimed to control onchocerciasis. This study attempts to determine factors associated with compliance to Community Directed Treatment with Ivermectin (CDTI and provides a basis for trying to understand how best to sustain long-term compliance in order to achieve success in the control of onchocerciasis. Methods An unmatched case-control study was conducted in Bebeka coffee plantation southwest Ethiopia. Cases were, compliant i.e., those individuals who had been registered on the relevant treatment registers and had taken all the five annual doses of Ivermectin. Controls were non-compliant, i.e. those individuals who had been recorded in the relevant treatment registers during the first treatment round(2003, and did not take at least two doses of which one being in the last treatment round (2007. Data were collected using a pre-tested interviewer administered structured questionnaire. Data were edited, cleaned, coded and analyzed using SPSS version 12.0.1 for Microsoft Windows. Multiple logistic regression models was used to identify factors associated with compliance to ivermectin. Results From the total of 456 individuals selected for administration of the survey questionnaire, 450(225 cases and 225 controls were contacted and completed the study 2 refused and 4 were unavailable. Five factors associated with compliance were identified: high risk perception [Adjusted Odds Ratio(AOR = 1.98, 95% Confidence Interval (CI, 1.32-2.95], one's family support [AOR = 1.86, 95% CI, 1.22-2.84], perceiving that the Community Drug Distributors (CDDs are doing their work well [AOR = 2.84, 95% CI, 1.50-5.37] and perceiving measuring height is the best way to determine a person's treatment dose [AOR = 6.37, 95% CI, 2
Bailey, Theodore C; Merritt, Maria W; Tediosi, Fabrizio
It has been suggested that initiatives to eradicate specific communicable diseases need to be informed by eradication investment cases to assess the feasibility, costs, and consequences of eradication compared with elimination or control. A methodological challenge of eradication investment cases is how to account for the ethical importance of the benefits, burdens, and distributions thereof that are salient in people's experiences of the diseases and related interventions but are not assessed in traditional approaches to health and economic evaluation. We have offered a method of ethical analysis grounded in theories of social justice. We have described the method and its philosophical rationale and illustrated its use in application to eradication investment cases for lymphatic filariasis and onchocerciasis, 2 neglected tropical diseases that are candidates for eradication.
Masud, Hannan; Qureshi, Tausif Qadir; Dukley, Meimei
To compare and analyze the effects of ivermectin with combined therapy of doxycycline and ivermectin on clinical symptoms of onchocerciasis. Randomized, comparative trial without blinding, a quasi-experimental study. Tubmenburg City (Bomy County) of Liberia, from March to December 2005. Two hundred and forty black local patients were included in clinical trial after recording their informed consent. Inclusion criteria was history of exposure to black fly in endemic area, symptoms of generalized and ocular itching, visual impairment associated with pannus and perilimbal pigmentation, punctuate/sclerosing keratitis, iridocyclitis, chorioretinitis, optic atrophy, lesions suggestive of onchodermatitis and subcutaneous nodules. Patients suffering from allergic conjunctivitis, history of measles and rubella, pregnant / breast-feeding women and children under 16 years of age were excluded from the study. The patients were randomly placed into two groups. Group I (120 patients) was treated with ivermectin in a single dose of 150 microg/kg orally. Group II (120 patients) was treated with combined therapy of doxycycline 100 mg/day for 6 weeks followed by ivermectin in a single dose of 150 microg/kg orally. Topical steroid-antibiotic combination was given to patients of both groups where indicated. Follow-up was carried out for 6 months. Improvement or progression of clinical features was recorded on each visit. Results were compiled and analysed by SPSS 10.0 using Chi-square test. Eighty four patients (70%) of group I and 117 (98%) patients of group II responded to treatment, with improvement in onchocerciasis clinical symptoms (p ivermectin as compared to those patients who were treated with ivermectin alone.
Yaya, G; Kobangué, L; Kémata, B; Gallé, D; Grésenguet, G
The authors return the results of a transverse prospective survey whose goal was to value the impact of struggle against the onchocerciasis after 20 years of distribution of ivermectin in a village of the Central African Republic. A transverse prospective survey with a descriptive and analytic aim of a sample of 393 topics aged of more than 5 years residing in Gami Village since more of 2 years and having benefitted the ivermectine in the last distribution that took place 10 months before. The epidemiological, clinical and parasitologic data introverted have been compared to the results of the previous investigations in the village. The parameters improved distinctly during the 20 years (1990-2010) notably the microfilarian indication (88% in 1990 against 19% in 2010), the middle microfilarian density (54 against 0,7), the CMFL Indication (39 against 0,67), the Knuttgen indication moved of the trance of age of 5-9 years to the one of more than 45 years since 1998), the cystic indication (36% against 8%), the ocular lesions (31% against 4%) of which onchocercian (28% against 2%), serious ocular lesions (16% against 1,3%), rate of blindness (9% against 0,8%), rate of meadow-blindness (9% against 0,8), important loss of vision (3% against 0,0%), ocular lesions in children of 6-10 years old (6% against 0,3%). These data permit to speak of control but not of elimination of the onchocerciasis in the grouping villager of Gami because of the persistence of the microfilarian indications susceptible to maintain the transmission of where necessity to pursue the struggle.
Emmanuel Uttah & Dominic C. Ibeh
Full Text Available Background & objectives: The study was aimed at determining the pattern of co-occurrence of species ofmicrofilaraemia between onchocerciasis endemic and sporadic populations.Methods: From every consenting person of one year and above, 50 μl of day and night blood samples werecollected and processed respectively with Haemotoxylin and Giemsa as vital stains. Two skin snips (one eachfrom the waist and the shoulder were also taken from these individuals and processed.Results: Results showed single species microfilaraemia (86.4 and 82.3%, double species microfilaraemia (12.2and 16.9% and triple species microfilaraemia (1.4 and 0.7% for endemic and sporadic populations respectively.All the species had single species microfilaraemia mostly, but Mansonella perstans and Loa loa showed greatestt endency towa rds doubl e and t r ipl e spe c i e s mi c rof i l a r a emi a . The pr eva l enc e of Wuche re r ia banc rof t imicrofilaraemia among those positive for Onchocerca volvulus was significantly lower than the overall prevalenceof Wuchereria bancrofti. Wuchereria bancrofti microfilaraemia was most common among those who had L. loamicrofilaraemia. Wuchereria bancrofti microfilarial intensity was higher among those with M. perstansmicrofilaraemia than among those positive for any of the other filarial species. Similarly, the intensity of M.perstans microfilaraemia among those positive for W. bancrofti exceeded the overall intensity of M. perstans.Conclusion: It is concluded that there was no definite pattern in mf densities discernible from co-occurrenceinfections either in the onchocerciasis endemic or sporadic population. There could be varied outcomes ofonchocerciasis infection attributable to positive or negative regulatory effects of other pathogens harbored bythe victims.
Young Eun Kim
Full Text Available Onchocerciasis (river blindness is a parasitic disease transmitted by blackflies. Symptoms include severe itching, skin lesions, and vision impairment including blindness. More than 99% of all cases are concentrated in sub-Saharan Africa. Fortunately, vector control and community-directed treatment with ivermectin have significantly decreased morbidity, and the treatment goal is shifting from control to elimination in Africa.We estimated financial resources and societal opportunity costs associated with scaling up community-directed treatment with ivermectin and implementing surveillance and response systems in endemic African regions for alternative treatment goals--control, elimination, and eradication. We used a micro-costing approach that allows adjustment for time-variant resource utilization and for the heterogeneity in the demographic, epidemiological, and political situation.The elimination and eradication scenarios, which include scaling up treatments to hypo-endemic and operationally challenging areas at the latest by 2021 and implementing intensive surveillance, would allow savings of $1.5 billion and $1.6 billion over 2013-2045 as compared to the control scenario. Although the elimination and eradication scenarios would require higher surveillance costs ($215 million and $242 million than the control scenario ($47 million, intensive surveillance would enable treatments to be safely stopped earlier, thereby saving unnecessary costs for prolonged treatments as in the control scenario lacking such surveillance and response systems.The elimination and eradication of onchocerciasis are predicted to allow substantial cost-savings in the long run. To realize cost-savings, policymakers should keep empowering community volunteers, and pharmaceutical companies would need to continue drug donation. To sustain high surveillance costs required for elimination and eradication, endemic countries would need to enhance their domestic funding capacity
Jones, B R; Anderson, J; Fuglsang, H
Increasing concentrations of levamisole and of mebendazole were applied to 1 eye in groups of 4 patients with ocular onchocerciasis in northern Cameroon. No effect resulted from up to 3.0% mebendazole suspensions, but 3.0% levamisole solutions rapidly caused entry of microfilariae, straightening out and subsequent opacification of previously curled-up living microfilariae, the rapid formation of typical limbal globular infiltrates, and the subsequent formation of fluffy opacities around the microfilariae. These changes are typical of all other drugs so far studied that have a microfilaricidal action on O. volvulus--diethlycarbamizine citrate (DEC), suramin, and metrifonate. The efficacy of 3.0% levamisole approximated to that of 0.03% DEC. This is in keeping with published observations on the filaricidal activity of these 2 compounds. It is suggested that this system of drug testing should be considered for systematic use in the search for more effective and safer drugs for onchocerciasis.
Twum-Danso, N A Y
In many areas of Africa where human onchocerciasis is endemic there are now programmes for mass treatment with ivermectin (Mectizan), to eliminate the disease as a public-health problem. To determine whether those with epilepsy and/or growth-retardation syndromes (GRS) should be excluded from such mass drug administrations, literature searches of the standard biomedical databases were performed for all relevant articles published in English or French before January 2003. Cross-referencing and the retrieving of articles recommended by experts completed the search. The literature review revealed that there is insufficient evidence for an association between onchocerciasis and epilepsy or GRS. Since ivermectin does not normally cross the blood-brain barrier, the drug is unlikely to have direct pro- or anti-convulsive activity. Furthermore, an estimated 1-2 million epileptics in Africa have been treated with ivermectin, in onchocerciasis-control programmes, without any reports of serious adverse events (SAE) to the passive surveillance system for such events. As there are few data on the prevalence of GRS in Africa, it is difficult to estimate the number of GRS cases who have been treated with ivermectin or the incidence of ivermectin-related SAE among such cases. Epileptics should not be excluded from mass treatments with ivermectin unless they are actively seizing or postictal. Although those with GRS associated with chronic wasting, with or without epilepsy, should be excluded, they should be eligible for clinic-based treatment if the diagnosis of onchocerciasis is confirmed and the benefits of treatment are deemed to outweigh any potential risks.
Stanimira P Krotneva
Full Text Available Since its initiation in 1995, the African Program for Onchocerciasis Control (APOC has had a substantial impact on the prevalence and burden of onchocerciasis through annual ivermectin mass treatment. Ivermectin is a broad-spectrum anti-parasitic agent that also has an impact on other co-endemic parasitic infections. In this study, we roughly assessed the additional impact of APOC activities on the burden of the most important off-target infections: soil-transmitted helminthiases (STH; ascariasis, trichuriasis, hookworm, and strongyloidiasis, lymphatic filariasis (LF, and scabies. Based on a literature review, we formulated assumptions about the impact of ivermectin treatment on the disease burden of these off-target infections. Using data on the number of ivermectin treatments in APOC regions and the latest estimates of the burden of disease, we then calculated the impact of APOC activities on off-target infections in terms of disability-adjusted life years (DALYs averted. We conservatively estimated that between 1995 and 2010, annual ivermectin mass treatment has cumulatively averted about 500 thousand DALYs from co-endemic STH infections, LF, and scabies. This impact comprised approximately an additional 5.5% relative to the total burden averted from onchocerciasis (8.9 million DALYs and indicates that the overall cost-effectiveness of APOC is even higher than previously reported.
Noma, Mounkaila; Zouré, Honorat G. M.; Bakoné, Lalle; Amazigo, Uche V.; de Vlas, Sake J.; Stolk, Wilma A.
Since its initiation in 1995, the African Program for Onchocerciasis Control (APOC) has had a substantial impact on the prevalence and burden of onchocerciasis through annual ivermectin mass treatment. Ivermectin is a broad-spectrum anti-parasitic agent that also has an impact on other co-endemic parasitic infections. In this study, we roughly assessed the additional impact of APOC activities on the burden of the most important off-target infections: soil-transmitted helminthiases (STH; ascariasis, trichuriasis, hookworm, and strongyloidiasis), lymphatic filariasis (LF), and scabies. Based on a literature review, we formulated assumptions about the impact of ivermectin treatment on the disease burden of these off-target infections. Using data on the number of ivermectin treatments in APOC regions and the latest estimates of the burden of disease, we then calculated the impact of APOC activities on off-target infections in terms of disability-adjusted life years (DALYs) averted. We conservatively estimated that between 1995 and 2010, annual ivermectin mass treatment has cumulatively averted about 500 thousand DALYs from co-endemic STH infections, LF, and scabies. This impact comprised approximately an additional 5.5% relative to the total burden averted from onchocerciasis (8.9 million DALYs) and indicates that the overall cost-effectiveness of APOC is even higher than previously reported. PMID:26401658
Katabarwa, Moses N; Katamanywa, James; Lakwo, Thomson; Habomugisha, Peace; Byamukama, Edson; Oguttu, David; Nahabwe, Christine; Ngabirano, Monica; Tukesiga, Ephraim; Khainza, Annet; Tukahebwa, Edridah; Unnasch, Thomas R; Richards, Frank O; Garms, Rolf
It was not until early 1990s that, when the Imaramagambo focus of southwest Uganda was mapped, mass treatment with a single annual dose of ivermectin for onchocerciaisis control commenced. However, comprehensive investigations on its transmission were launched after a nationwide policy for onchocerciasis elimination in 2007. Entomological surveys throughout the focus from 2007 to 2015 have yielded few or no freshwater crabs (Potamonautes aloysiisabaudiae), which serve as the obligate phoretic host of the larvae and pupae of the vector Simulium neavei No S. neavei flies have been observed or collected since 2007. Skin snips (microscopy) from 294 individuals in 2008 were negative for skin microfilariae, and of the 462 persons analyzed by polymerase chain reaction skin snip poolscreen in 2009, only five (1.08%) persons were indicated as infected with onchocerciasis. All five of the positive persons were at least 40 years old. Serosurvey results showed negative exposure among 3,332 children in 2012 and 3,108 children in 2015. Both were within the upper bound of the 95% confidence interval of the prevalence estimate of 0.06%, which confirmed the elimination of onchocerciasis. Treatment coverage in Imaramagambo was generally poor, and transmission interruption of onchocerciasis could not be attributed solely to annual mass treatment with ivermectin. There was sufficient evidence to believe that the possible disappearance of the S. neavei flies, presumed to have been the main vector, may have hastened the demise of onchocerciasis in this focus.
White, A T; Newland, H S; Taylor, H R; Erttmann, K D; Keyvan-Larijani, E; Nara, A; Aziz, M A; D'Anna, S A; Williams, P N; Greene, B M
Ivermectin, given as a single oral dose, has shown considerable promise as a new treatment for onchocerciasis. We assessed the safety and efficacy of ivermectin and tried to determine the optimal dose. Two hundred Liberians received 100, 150, or 200 micrograms of ivermectin/kg or placebo and were followed up for 12 months. Therapy was associated with only minimal systemic and ocular side effects. A 200-micrograms/kg dose was associated with greater systemic reaction than was a 100-micrograms/kg dose. Each treatment group had significant reduction in skin microfilaria counts by day 3 and a decrease of approximately 95% at three months. At three months the proportion of persons with no microfilariae in a specimen of skin was significantly less in the 100-micrograms/kg group than in the 150-micrograms/kg or 200-micrograms/kg groups. At 12 months, the level of microfilariae in skin was still reduced approximately 80%. Significant reduction in ocular involvement was seen in all groups. These results confirm that single-dose ivermectin is effective and well-tolerated and suggest that 150 micrograms of ivermectin/kg may be the optimal dose for initial therapy.
Nwoke, B E; Onwuliri, C O; Ufomadu, G O
The physico-biological ecological complex in Plateau State has by definition increased the potential of most rivers to support the breeding and dispersal of vector species as well as human acquisition and dissemination of the disease for several months in a year. Though villagers in endemic areas are of the know of the nuisance of blackfly bites, but the majority of them lacked the aetiological knowledge of onchocercal lesion. Hence disease management is misdirected towards consulting the oracle and appeasing the gods. The vectors of onchocerciasis in Plateau State, S. damnosum, and S. sirbanum are wet season breeders with their peak biting density occurring at the height of rainy season. However, biting flies carry more infective parasites at the beginning and end of rain. These vectors exhibit bimodal biting activity: a small one in the morning hours and a pronounced evening peak. Biting activity is at least influenced by two major climatic factors; illumination and temperature. However, the fastest changing climatic factor relative to an increase in the biting activity of flies was illumination. Microfilarial load in the skin of patients does not significantly change throughout the year or when biopsies are taken under shade throughout the day. Extreme temperatures, however, have significant reducing effect on the skin microfilarial. The epidemiological relevance of these in the ongoing MECTIZAN delivery in the State are discussed.
Luc E Coffeng
Full Text Available The African Programme for Onchocerciasis Control (APOC is currently shifting its focus from morbidity control to elimination of infection. To enhance the likelihood of elimination and speed up its achievement, programs may consider to increase the frequency of ivermectin mass treatment from annual to 6-monthly or even higher. In a computer simulation study, we examined the potential impact of increasing the mass treatment frequency for different settings. With the ONCHOSIM model, we simulated 92,610 scenarios pertaining to different assumptions about transmission conditions, history of mass treatment, the future mass treatment strategy, and ivermectin efficacy. Simulation results were used to determine the minimum remaining program duration and number of treatment rounds required to achieve 99% probability of elimination. Doubling the frequency of treatment from yearly to 6-monthly or 3-monthly was predicted to reduce remaining program duration by about 40% or 60%, respectively. These reductions come at a cost of additional treatment rounds, especially in case of 3-monthly mass treatment. Also, aforementioned reductions are highly dependent on maintained coverage, and could be completely nullified if coverage of mass treatment were to fall in the future. In low coverage settings, increasing treatment coverage is almost just as effective as increasing treatment frequency. We conclude that 6-monthly mass treatment may only be worth the effort in situations where annual treatment is expected to take a long time to achieve elimination in spite of good treatment coverage, e.g. because of unfavorable transmission conditions or because mass treatment started recently.
Vieira, J C; Brackenboro, L; Porter, C H; Basáñez, M-G; Collins, R C
The influence of spatial and temporal factors on onchocerciasis transmission by Simulium exiguum s.l. and S. quadrivittatum in Ecuador was investigated to help develop sampling protocols for entomological surveillance of ivermectin programmes. Flies were collected in alternate months (November 1995-November 1996) at four sites each in the hyperendemic communities of San Miguel and El Tigre. A fixed-effects analysis of variance was used to explore the influence on vector abundance of locality, site, month and hour. Infectivity rates detected by dissection and PCR assays were compared. Simulium exiguum s.l. predominated at El Tigre (75%) whereas S. quadrivittatum prevailed at San Miguel (62%). Vector abundance was highest on river banks and outside houses. Biting and infection rates peaked from March to July. Hourly activity patterns were bimodal in S. exiguum but unimodal in S. quadrivittatum. Annual transmission potentials (ATP) for both species combined were 385 and 733 third stage larvae/person in San Miguel and El Tigre respectively, with S. exiguum accounting for 80% of the combined ATP at both localities. We recommend protocols that may maximize detection of parasite transmission. Infection rates thus obtained must be linked with vector density estimates to assess meaningfully host exposure as treatment progresses.
Full Text Available Histological examination of a nodule removed from the back of the hand of a 58-year-old woman from Oita, Kyushu, Japan showed an Onchocerca female sectioned through the posterior region of the worm (ovaries identifiable and young (thin cuticle. Six Onchocerca species are enzootic in that area: O. gutturosa and O. lienalis in cattle, O. suzukii in serows (Capricornis crispus, O. skrjabini and an Onchocerca sp. in Cervus nippon nippon, and O. dewittei japonica in wild boar (Sus scrofa leucomystax. Diagnostic charactets of female Onchocerca species, such as the cuticle and its ridges, change along the body length. Tables of the histologic morphology of the mid- and posterior body-regions of the local species are presented. In addition, it was observed that transverse ridges arose and thickened during the adult stage (examination of fourth stage and juvenile females of O. volvulus. The specimen described in this report, with its prominent and widely spaced ridges, was identified as O. d. japonica. Four of the 10 zoonotic cases of onchocerciasis reported worldwide were from Oita, three of them being caused by O. d. japonica, the prevalence of which in local wild boar was 22 of 24 (92 %.
Karam, M; Weiss, N
Immunological study of individuals (aged 4 to 70 years) living in an area of Mali hyperendemic for onchocerciasis revealed an 83% prevalence of skin microfilariae (mf). Microfilariae counts from skin snips were highly age-dependent. Screening for concomitant helminth infections showed a low prevalence of hookworms and Mansonella (Dipetalonema) perstans, but neither schistosomiasis nor bancroftian filariasis. Immunological results revealed strong correlation between radioallergosorbent test (RAST) and skin test (5 and 50 ng adult O. volvulus extract), between RAST and total IgE, and between IFAT and ELISA. A negative correlation exists between mf counts and skin tests and between mf counts and RAST; the lowest median values were obtained in the group with high mf counts. Skin sensitizing antibodies were detected in most locally born children aged 4-5 years. Intradermal tests showed a high rate of sensitization to O. volvulus antigen in mf-negative children, whereas ELISA and IFAT values were significantly lower in these children than in mf-positive children. Increasing concentrations of circulating IgE antibodies were found in children aged 4-11 years by RAST, and, in individuals aged 12-19 years (age group for which mf counts sharply increase), skin testing revealed a state of anergy. In long lasting infections (adults greater than 20 years) skin reactivity was comparable to that of young children or was depressed. ELISA and IFAT achieved similar results in each age group.
Awadzi, K; Adjepon-Yamoah, K K; Edwards, G; Orme, M L; Breckenridge, A M; Gilles, H M
Twenty-one patients with moderate to heavy infections with O. volvulus were treated with 25 mg of diethylcarbamazine (DEC) citrate twice daily for 10 days. In 11 patients the urine was made alkaline with sodium bicarbonate, 2 g, administered 6 hourly for three doses daily beginning 1 day before DEC was started and continued throughout the DEC therapy. Ten patients served as controls. The mean pre-dose plasma DEC concentration during treatment and the mean plasma DEC half-life were significantly higher in bicarbonate treated patients as compared to controls. Total urinary excretion of DEC was significantly less in the bicarbonate treated group than in controls. Mean overall total reaction was higher in bicarbonate-treated patients but the difference was not significant. The bicarbonate-treated group achieved a significantly greater reduction in skin microfilarial counts than the control group as assessed 1 week after completion of therapy, but there was little difference at 1 month. Microfilarial killing was associated with microfilarial mobilisation, alteration in peripheral leucocytes and elevation in serum aminotransferases in both groups. There was no effect of DEC on the number of adult worms recovered in nodules removed at the end of the therapy. This study indicates that moderate urinary alkalinisation alters the kinetics of DEC and the therapeutic response. However the severity of clinical reaction coupled with the inadequate level of microfilarial killing achieved make it unlikely that manipulation of urinary pH will be of practical value in onchocerciasis chemotherapy.
Full Text Available BACKGROUND: Mass treatment with ivermectin is a proven strategy for controlling onchocerciasis as a public health problem, but it is not known if it can also interrupt transmission and eliminate the parasite in endemic foci in Africa where vectors are highly efficient. A longitudinal study was undertaken in three hyperendemic foci in Mali and Senegal with 15 to 17 years of annual or six-monthly ivermectin treatment in order to assess residual levels of infection and transmission and test whether ivermectin treatment could be safely stopped in the study areas. METHODOLOGY/PRINCIPAL FINDINGS: Skin snip surveys were undertaken in 126 villages, and 17,801 people were examined. The prevalence of microfilaridermia was <1% in all three foci. A total of 157,500 blackflies were collected and analyzed for the presence of Onchocerca volvulus larvae using a specific DNA probe, and vector infectivity rates were all below 0.5 infective flies per 1,000 flies. Except for a subsection of one focus, all infection and transmission indicators were below postulated thresholds for elimination. Treatment was therefore stopped in test areas of 5 to 8 villages in each focus. Evaluations 16 to 22 months after the last treatment in the test areas involved examination of 2,283 people using the skin snip method and a DEC patch test, and analysis of 123,000 black flies. No infected persons and no infected blackflies were detected in the test areas, and vector infectivity rates in other catching points were <0.2 infective flies per 1,000. CONCLUSION/SIGNIFICANCE: This study has provided the first empirical evidence that elimination of onchocerciasis with ivermectin treatment is feasible in some endemic foci in Africa. Although further studies are needed to determine to what extent these findings can be extrapolated to other endemic areas in Africa, the principle of elimination has been established. The African Programme for Onchocerciasis Control has adopted an additional
Gloeckner, Christian; Garner, Amanda L; Mersha, Fana; Oksov, Yelena; Tricoche, Nancy; Eubanks, Lisa M; Lustigman, Sara; Kaufmann, Gunnar F; Janda, Kim D
Onchocerciasis, or river blindness, is a neglected tropical disease caused by the filarial nematode Onchocerca volvulus that affects more than 37 million people, mainly in third world countries. Currently, the only approved drug available for mass treatment is ivermectin, however, drug resistance is beginning to emerge, thus, new therapeutic targets and agents are desperately needed to treat and cure this devastating disease. Chitin metabolism plays a central role in invertebrate biology due to the critical structural function of chitin for the organism. Taken together with its absence in mammals, targeting chitin is an appealing therapeutic avenue. Importantly, the chitinase OvCHT1 from O. volvulus was recently discovered, however, its exact role in the worm's metabolism remains unknown. A screening effort against OvCHT1 was conducted using the Johns Hopkins Clinical Compound Library that contains over 1,500 existing drugs. Closantel, a veterinary anthelmintic with known proton ionophore activities, was identified as a potent and specific inhibitor of filarial chitinases, an activity not previously reported for this compound. Notably, closantel was found also to completely inhibit molting of O. volvulus infective L3 stage larvae. Closantel appears to target two important biochemical processes essential to filarial parasites. To begin to unravel closantel's effects, a retro-fragment-based study was used to define structural elements critical for closantel's chitinase inhibitor function. As resources towards the development of new agents that target neglected tropical diseases are scant, the finding of an existing drug with impact against O. volvulus provides promise in the hunt for new therapies against river blindness.
Christina A Bulman
Full Text Available Two major human diseases caused by filariid nematodes are onchocerciasis, or river blindness, and lymphatic filariasis, which can lead to elephantiasis. The drugs ivermectin, diethylcarbamazine (DEC, and albendazole are used in control programs for these diseases, but are mainly effective against the microfilarial stage and have minimal or no effect on adult worms. Adult Onchocerca volvulus and Brugia malayi worms (macrofilariae can live for up to 15 years, reproducing and allowing the infection to persist in a population. Therefore, to support control or elimination of these two diseases, effective macrofilaricidal drugs are necessary, in addition to current drugs. In an effort to identify macrofilaricidal drugs, we screened an FDA-approved library with adult worms of Brugia spp. and Onchocerca ochengi, third-stage larvae (L3s of Onchocerca volvulus, and the microfilariae of both O. ochengi and Loa loa. We found that auranofin, a gold-containing drug used for rheumatoid arthritis, was effective in vitro in killing both Brugia spp. and O. ochengi adult worms and in inhibiting the molting of L3s of O. volvulus with IC50 values in the low micromolar to nanomolar range. Auranofin had an approximately 43-fold higher IC50 against the microfilariae of L. loa compared with the IC50 for adult female O. ochengi, which may be beneficial if used in areas where Onchocerca and Brugia are co-endemic with L. loa, to prevent severe adverse reactions to the drug-induced death of L. loa microfilariae. Further testing indicated that auranofin is also effective in reducing Brugia adult worm burden in infected gerbils and that auranofin may be targeting the thioredoxin reductase in this nematode.
Henson, P. M.; Mackenzie, C. D.; Spector, W. G.
This report concerns the host's reactions to the presence of the parasite both in the course of the natural disease and during drug treatment. The various stages of Onchocerca volvulus are discussed in terms of the type of tissue reaction seen. The discussion then turns to basic hypotheses concerning the etiology of these reactions, emphasis being placed on the fact that while pathological changes are considerable in some locations there is a remarkable lack of reaction in others. Some of the mechanisms possibly involved in this apparent absence of host response are discussed, including anti-complement factors, poor antigenicity, acquisition of host antigen, immune tolerance, and blocking antibodies. In any study of the inflammatory response it is recommended that critical evaluations be made of histological material, haematological studies, the definition of the antigenic nature of O. volvulus, characterization of immunological reactivity of patients, and the definition of the migratory pathways of the parasite. The marked host reactions seen following chemotherapy, especially those related to the interaction of the drug diethylcarbamazine with microfilariae, are discussed at some length. The etiology of these reactions is considered and recommendations are made for the experimental elucidation of the mechanisms involved. Emphasis is placed on the necessity for detailed sequential histopathological and immunopathological studies in the definition of the tissue lesions found in onchocerciasis. Characterization of these lesions will assist greatly the approach to control of the adverse reactions seen during treatment. The use of anti-inflammatory agents in clinical trials is discussed and comments are made concerning the most suitable clinical situations for testing drugs and the types of drug that should be tested. PMID:396050
Henson, P M; Mackenzie, C D; Spector, W G
This report concerns the host's reactions to the presence of the parasite both in the course of the natural disease and during drug treatment. The various stages of Onchocerca volvulus are discussed in terms of the type of tissue reaction seen. The discussion then turns to basic hypotheses concerning the etiology of these reactions, emphasis being placed on the fact that while pathological changes are considerable in some locations there is a remarkable lack of reaction in others. Some of the mechanisms possibly involved in this apparent absence of host response are discussed, including anti-complement factors, poor antigenicity, acquisition of host antigen, immune tolerance, and blocking antibodies. In any study of the inflammatory response it is recommended that critical evaluations be made of histological material, haematological studies, the definition of the antigenic nature of O. volvulus, characterization of immunological reactivity of patients, and the definition of the migratory pathways of the parasite.The marked host reactions seen following chemotherapy, especially those related to the interaction of the drug diethylcarbamazine with microfilariae, are discussed at some length. The etiology of these reactions is considered and recommendations are made for the experimental elucidation of the mechanisms involved. Emphasis is placed on the necessity for detailed sequential histopathological and immunopathological studies in the definition of the tissue lesions found in onchocerciasis. Characterization of these lesions will assist greatly the approach to control of the adverse reactions seen during treatment.The use of anti-inflammatory agents in clinical trials is discussed and comments are made concerning the most suitable clinical situations for testing drugs and the types of drug that should be tested.
G.J.J.M. Borsboom (Gerard); B.A. Boatin (Boakye); N.J.D. Nagelkerke (Nico); H. Agoua (Hyacinthe); K.L.B. Akpoboua (Komlan); E.W. Soumbey Alley (E. William); Y. Bissan (Yeriba); A. Renz (Anna); L. Yameogo (Laurent); J.H.F. Remme (Jan); J.D.F. Habbema (Dik)
markdownabstract__Background:__ The Onchocerciasis Control Program (OCP) in West Africa has been closed down at the end of 2002. All subsequent control will be transferred to the participating countries and will almost entirely be based on periodic mass treatment with ivermectin. This makes the ques
Vouking, Marius Zambou; Tamo, Violette Claire; Tadenfok, Carine Nouboudem
The African Program for Onchocerciasis Control (APOC) was launched in 1995 with the main goal being to boost the fight against onchocerciasis in Africa. In 2011, over 80 million people benefited from this intervention thanks to the contribution of 268.718 Community-Directed Distributors (CDD). These significant results obscure the role of women CDD in this fight. Indeed, the insufficient involvement of female CDD has been identified as a concern by the APOC partners early in the program. The present study aims to assess the contribution and performance of women involved in a strategy to control onchocerciasis by community-directed treatment with ivermectin in sub Saharan Africa. We searched the following electronic databases from January 1995 to July 2013: Medline, Embase (Excerpta Medica Database), CINAHL (Cumulative Index to Nursing and Allied Health Literature), LILAS (Latin American and Caribbean Literature on Health Sciences), International Bibliography of Social Sciences, Social Services Abstracts, and Sociological Abstracts. Two research team members independently conducted data extraction from the final sample of articles by using a pre-established data extraction sheet. The primary outcome was the contribution of female CDD in the control of onchocerciasis by community-directed treatment with Ivermectin. Of 25 hits, 7 papers met the inclusion criteria. For the management of onchocerciasis, female CDDs are elected by the health committee from the communities they will serve. The significant proportion of those treated (about 61%) were women, although only 24% of CDDs were women. Many community members reported that women were more committed, persuasive and more patient than men in the distribution of ivermectin. Some studies have identified underutilization of female CDD as one reason for the limited effectiveness or, in some cases, pure failure related to the distribution of Ivermectin interventions in the fight against onchocerciasis in sub-Saharan Africa
Arzube, M E
The first endemic focus of onchocerciasis in Ecuador has been established in the province of Esmeraldas. It is on the Cayapas River about 85 kilometer upstream from the town of Borbón. The endemic focus as far as it is currently known, appears to be localized between the settlements of Sapallo Grande and San Miguel de Cayapas. 87 persons were examined in both settlements. Onchocerciasis was detected in 72 (83%) persons; 62 (86%) were negroes and 10 were Cayapas indians; 42 (58%) were males and 30 were females. 29 (74%) of the weighed skin snips taken from 39 individuals showed a higher microfilarial density from the iliac crest than from the scapula. The following clinical manifestations were found in the positive cases: 45 (63%) with onchocercoma; 31 (43%) with dermatitis, pigmentary changes, atrophy of the skin; 19 (26%) with lymphoadenopathy and lymphoedema of the external genital organs; 32 (44%) with corneal opacities; 49 (68%) with itching of the skin and dermatitis and 23 (32%) without itching but with dermatitis. 274 Simulium were collected biting man. Three species were identified, although the specific names used must be considered as provisional. 59 S. exiguum, 206 S. quadrivittatum and 9 S. antillarum. The black flies were attracted with human bait inside the houses, outside and around the houses and at 500 meters far from the house near a creek. It seems that the three species are anthropophilic and endophilic.
Joy R Guderian
Full Text Available The prevalence of onchocerciasis infection was determined in communities on 7 rivers located in the northern area of the cantón San Lorenzo, province of Esmeraldas. Diagnosis of the infection was obtained by skin biopsies and recombinant-antigen based-serology. No evidence of infection was detected in 9 communities studied along the Río Mataje, which forms the frontier between Ecuador and Colombia, nor in 10 adjacent communities located on 5 interior rivers. Evidence for Onchocerca volvulus infection was found in 4 communities on the Río Tululví with the following prevalence: La Boca (3.5% by biopsy and 3.9% by serology, Guayabal (9.1% by both biopsy and serology, La Ceiva (51.5% by biopsy and 53% by serology, and Salidero (4% by biopsy and 7.7% by serology. A few individuals in these communities were seropositive for O. volvulus in the absence of detectable dermal microfilariae: these might harbor very light or prepatent infections. No clinical disease attributable to onchocerciasis was found. The infected communities will be included in the ivermectin-based National Control Program for the disease, with no evidence of the infection having extended north of the Ecuadorian-colombian border
Hagan, J B; Bartemes, K R; Kita, H; Ottesen, E A; Awadzi, K; Nutman, T B; Gleich, G J
The eosinophil survival assay was used to quantitate cytokines in 17 serial serum samples from 10 patients treated for onchocerciasis with diethylcarbamazine. Eosinophils isolated from normal donors were cultured for 4 days in the presence of patients' sera, and cell viability was determined. Serum specimens from 9 of 10 patients enhanced eosinophil survival from 4.8% +/- 2.2% (mean +/- SE) before treatment to 50.0% +/- 6.4% after treatment. Survival enhancement activity peaked before posttreatment eosinophilia. Antibodies to interleukin (IL)-5, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-3 were used to block cytokine activity in 22 serum samples. Antibodies to IL-5 blocked survival in 5 samples, antibodies to GM-CSF blocked survival in 6 samples, and a combination of antibodies to IL-5 and GM-CSF blocked survival in 8 additional samples. Overall, posttreatment sera from patients treated for onchocerciasis enhanced eosinophil survival; both GM-CSF and IL-5 may promote the posttreatment eosinophilia in filarial infection.
Albiez, E J; Newland, H S; White, A T; Kaiser, A; Greene, B M; Taylor, H R; Büttner, D W
Fifty adult male subjects with moderate to heavy onchocerciasis from the Liberian rain forest were selected for a double-blind placebo-controlled chemotherapy study. The effects of high doses of diethylcarbamazine (DEC) - 30 mg/kg/d - over one week preceded by a one week initial treatment with normal oral doses of DEC or DEC lotion were compared with a single dose of ivermectin (150 micrograms/kg) and placebo. During the initial treatment DEC tablets or lotion caused distinctly more frequent and severe reactions than did invermectin. The reactions to ivermectin did not differ from those of the placebo patients. High doses of DEC caused, in about half of the patients, headache, dizziness, nausea or vomiting. DEC markedly increased the number of corneal microfilariae and of corneal opacities compared to ivermectin. All changes resolved with a return to pretreatment findings two months after treatment. The three treatment groups showed no differences at the ten months follow-up. In all treated patients skin microfilaria counts fell almost to zero by the end of the two week therapy. In the ivermectin group microfilaria counts remained significantly lower than in the DEC patients at the two and ten months examinations. In summary, ivermectin was much better tolerated than DEC and had a longer lasting effect on the microfilariae in the skin. Since high doses of DEC were less effective and caused more frequent and severe side effects, this approach cannot be recommended for treatment of onchocerciasis.
Knab, J; Darge, K; Büttner, D W
The role of macrophages in the killing and elimination of microfilariae (mf) was studied immunohistologically in 14 lymph nodes from 10 patients with generalized onchocerciasis 20-68 h after treatment with a single oral dose of 150 microg/kg ivermectin. Mf with signs of damage at light microscopical level were surrounded by a cellular infiltrate comprising macrophages, eosinophils and neutrophils, whereas light microscopically intact mf mostly showed no cellular reaction. Resident mature macrophages expressing the CD 68 epitope usually neither migrated nor attached to damaged mf, especially on the first and second day after ivermectin treatment. However, many young invading macrophages labelled for the L1 protein (antibodies 27 E 10, MAC 387, S 36.48 and 8.5C2) were found within the cellular infiltrate around damaged mf and in adherence to the mf in all lymph nodes after ivermectin treatment. Free L1 protein was observed on the cuticle of the mf. The attacking macrophages contained increased amounts of the enzymes lysozyme, alpha-1-antichymotrypsin and alpha-1-antitrypsin compared to resident macrophages. Free enzymes were found on the cuticle of the mf and around them, indicating a role of these enzymes in the inflammatory reaction to the parasites. The attacking macrophages were strongly labelled for human HLA-DR and they showed further an increased expression of the complement receptors CR1 (CD 35) for C3b and CR3 (CD 11b) for C3 bi in comparison to resident macrophages and thus were considered as activated macrophages. Rarely fragments of mf were seen within multinuclear macrophages. We conclude that young activated macrophages play a major role in the elimination of mf transported to the regional lymph nodes after ivermectin treatment. The immunohistological findings are in accordance with the assumption that these activated macrophages together with granulocytes contribute to the killing of the damaged mf. They also help to limit the damage of the host tissue
Ackerman, S J; Kephart, G M; Francis, H; Awadzi, K; Gleich, G J; Ottesen, E A
Onchocerciasis patients treated with diethylcarbamazine often undergo a severe inflammatory response, the Mazzotti reaction. To assess the eosinophil's role in the pathogenesis of the Mazzotti reaction, we obtained serial blood, plasma, and skin biopsy specimens from 21 heavily infected patients and 3 endemic controls, both before and during therapy with diethylcarbamazine. Samples were analyzed for blood eosinophils, plasma levels of eosinophil granule major basic protein (MBP) and eosinophil-derived neurotoxin, eosinophil infiltration and eosinophil and mast cell degranulation in the skin. After the first dose of diethylcarbamazine, blood eosinophils fell from a pre-treatment level of 888 +/- 111 to 203 +/- 42 cells/mm3 at 8 h. This decrease was followed by a marked eosinophilia developing over the remaining 7 days of treatment and 14 days of follow-up. Plasma eosinophil-derived neurotoxin levels increased from 56 +/- 4 ng/ml pretreatment to a peak of 82 +/- 9 ng/ml at 8 h and returned to pretreatment levels by 48 h. Beginning at 12 h, plasma MBP levels increased from 730 +/- 74 ng/ml pretreatment to a peak of 1140 +/- 74 ng/ml after 5 days. Pretreatment skin biopsies stained for MBP by immunofluorescence showed a bright fibrillar pattern in the dermis consistent with chronic eosinophil degranulation; the MBP was localized on elastic tissue fibers. After treatment, skin biopsy specimens showed both the pretreatment fibrillar MBP staining pattern as well as focal eosinophil degranulation. Deposition of MBP around microfilariae in the papillary dermis was visible as early as 1.5 h. The lowest blood eosinophil levels and peak plasma eosinophil-derived neurotoxin levels coincided with the infiltration and degranulation of eosinophils in the skin. Mast cell degranulation in the skin was maximal by the first posttreatment biopsy (1.5 h) coincident with the beginning of eosinophil degranulation. Although the pathogenesis of the Mazzotti reaction is clearly complex, our
Mekonnen, Solomon A; Beissner, Marcus; Saar, Malkin; Ali, Solomon; Zeynudin, Ahmed; Tesfaye, Kassahun; Adbaru, Mulatu G; Battke, Florian; Poppert, Sven; Hoelscher, Michael; Löscher, Thomas; Bretzel, Gisela; Herbinger, Karl-Heinz
Onchocerciasis is a parasitic disease caused by the filarial nematode Onchocerca volvulus. In endemic areas, the diagnosis is commonly confirmed by microscopic examination of skin snip samples, though this technique is considered to have low sensitivity. The available melting-curve based quantitative real-time PCR (qPCR) using degenerated primers targeting the O-150 repeat of O. volvulus was considered insufficient for confirming the individual diagnosis, especially in elimination studies. This study aimed to improve detection of O. volvulus DNA in clinical samples through the development of a highly sensitive qPCR assay. A novel hydrolysis probe based qPCR assay was designed targeting the specific sequence of the O. volvulus O-5S rRNA gene. A total of 200 clinically suspected onchocerciasis cases were included from Goma district in South-west Ethiopia, from October 2012 through May 2013. Skin snip samples were collected and subjected to microscopy, O-150 qPCR, and the novel O-5S qPCR. Among the 200 individuals, 133 patients tested positive (positivity rate of 66.5%) and 67 negative by O-5S qPCR, 74 tested positive by microscopy (37.0%) and 78 tested positive by O-150 qPCR (39.0%). Among the 133 O-5S qPCR positive individuals, microscopy and O-150 qPCR detected 55.6 and 59.4% patients, respectively, implying a higher sensitivity of O-5S qPCR than microscopy and O-150 qPCR. None of the 67 individuals who tested negative by O-5S qPCR tested positive by microscopy or O-150 qPCR, implying 100% specificity of the newly designed O-5S qPCR assay. The novel O-5S qPCR assay is more sensitive than both microscopic examination and the existing O-150 qPCR for the detection of O. volvulus from skin snip samples. The newly designed assay is an important step towards appropriate individual diagnosis and control of onchocerciasis.
Gardon, J; Gardon-Wendel, N; Demanga-Ngangue; Kamgno, J; Chippaux, J P; Boussinesq, M
In 1995, the World Bank launched an African Programme for Onchocerciasis Control to eliminate Onchocerca volvulus disease from 19 African countries by means of community-based ivermectin treatment (CBIT). Several cases of encephalopathy have been reported after ivermectin in people heavily infected with microfilariae of Loa loa (loiasis). We assessed the incidence of serious events in an area where onchocerciasis and loiasis are both endemic. Ivermectin (at 150 micrograms/kg) was given to 17877 people living in the Lékié area of Cameroon. 50 microL samples of capillary blood were taken during the daytime before treatment from all adults (aged > or = 15 years), and the numbers of L loa and Mansonella perstans microfilariae in them were counted. Patients were monitored for 7 days after treatment. Adverse reactions were classified as mild, marked, or serious. Serious reactions were defined as those associated with a functional impairment that required at least a week of full-time assistance to undertake normal activities. We calculated the relative risk of developing marked or serious reactions for increasing L loa microfilarial loads. Risk factors for serious reactions were identified and assessed with a logistic regression model. 20 patients (0-11%) developed serious reactions without neurological signs but associated with a functional impairment lasting more than a week. Two other patients were in coma for 2-3 days, associated with L loa microfilariae in cerebrospinal fluid. Occurrence of serious reactions was related to the intensity of pretreatment L loa microfilaraemia. The relative risk of developing marked or serious reactions was significantly higher when the L loa load exceeded 8000 microfilariae/mL; for serious reactions, the risk is very high (odds ratio > 1000) for loads above 50000 microfilariae/mL. Epidemiological surveys aimed at assessing the intensity of infection with L loa microfilariae should be done before ivermectin is distributed for
Darge, K; Lucius, R; Monson, M H; Behrendsen, J; Büttner, D W
Microfilariae were studied in skin and lymph node biopsies from Liberian patients with generalised onchocerciasis 12-78 hours after administration of a single dose of 150 micrograms/kg body weight using histology, transmission electron microscopy and immunocytological staining with antibodies against an immunodominant antigen of Onchocerca volvulus. Most microfilariae in the skin appeared morphologically intact and beginning signs of degeneration were seen only on the ultrastructural level. The densities of microfilariae in the lymph nodes were about thousandfold higher in ivermectin treated patients. More than 90% of the microfilariae in the lymph nodes showed distinct signs of degeneration. Early changes were seen in the muscle cells. The disintegrating microfilariae in the lymph nodes were always encircled by eosinophils or macrophages or both cells. Immunohistological staining with antifilarial antibodies increased the detection of small and disintegrating pieces of microfilariae considerably.
Philip J Cooper
Full Text Available Trends in prevalence rates of onchocercal ocular lesions were examined over the period 1980 to 1990 using data from two cross-sectional surveys. There was evidence for increasing prevalence of anterior chamber microfilariae, iridocyclitis, optic atrophy, and chorioretinopathy. Large increases in prevalence, in particular, were seen for posterior segment lesions: optic atrophy increased from 2.7% to 6.4% and chorioretinopathy from 8.8% to 35.6%. Greatest increases in these lesions were seen in the Chachi which was attributed to the large increases in prevalence of microfilariae in the anterior chamber particularly in those aged 30 years or greater. The study findings suggest that ocular onchocerciasis is evolving in parallel with the well documented parasitological changes.
Full Text Available INTRODUCTION: A clinically significant endemic focus of onchocerciasis existing in Esmeraldas Province, coastal Ecuador has been under an ivermectin mass drug administration program since 1991. The main transmitting vector in this area is the voracious blackfly, Simulium exiguum. This paper describes the assessments made that support the decision to cease mass treatment. METHODOLOGY AND PRINCIPLE FINDINGS: Thirty-five rounds of ivermectin treatment occurred between 1991-2009 with 29 of these carrying >85% coverage. Following the guidelines set by WHO for ceasing ivermectin distribution the impact on parasite transmission was measured in the two vector species by an O-150 PCR technique standard for assessing for the presence of Onchocerca volvulus. Up to seven collection sites in three major river systems were tested on four occasions between 1995 and 2008. The infectivity rates of 65.0 (CI 39-101 and 72.7 (CI 42-116 in 1995 dropped to zero at all seven collection sites by 2008. Assessment for the presence of antibodies against O. volvulus was made in 2001, 2006, 2007 and 2008 using standard ELISA assays for detecting anti-Ov16 antibodies. None of total of 1810 children aged 1-15 years (between 82 and 98% of children present in the surveyed villages tested in the above years were found to be carrying antibodies to this antigen. These findings were the basis for the cessation of mass drug treatment with ivermectin in 2009. SIGNIFICANCE: This fulfillment of the criteria for cessation of mass distribution of ivermectin in the only known endemic zone of onchocerciasis in Ecuador moves the country into the surveillance phase of official verification for national elimination of transmission of infection. These findings indicate that ivermectin given twice a year with greater than 85% of the community can move a program to the final stages of verification of transmission interruption.
Lovato, Raquel; Guevara, Angel; Guderian, Ronald; Proaño, Roberto; Unnasch, Thomas; Criollo, Hipatia; Hassan, Hassan K; Mackenzie, Charles D
A clinically significant endemic focus of onchocerciasis existing in Esmeraldas Province, coastal Ecuador has been under an ivermectin mass drug administration program since 1991. The main transmitting vector in this area is the voracious blackfly, Simulium exiguum. This paper describes the assessments made that support the decision to cease mass treatment. Thirty-five rounds of ivermectin treatment occurred between 1991-2009 with 29 of these carrying >85% coverage. Following the guidelines set by WHO for ceasing ivermectin distribution the impact on parasite transmission was measured in the two vector species by an O-150 PCR technique standard for assessing for the presence of Onchocerca volvulus. Up to seven collection sites in three major river systems were tested on four occasions between 1995 and 2008. The infectivity rates of 65.0 (CI 39-101) and 72.7 (CI 42-116) in 1995 dropped to zero at all seven collection sites by 2008. Assessment for the presence of antibodies against O. volvulus was made in 2001, 2006, 2007 and 2008 using standard ELISA assays for detecting anti-Ov16 antibodies. None of total of 1810 children aged 1-15 years (between 82 and 98% of children present in the surveyed villages) tested in the above years were found to be carrying antibodies to this antigen. These findings were the basis for the cessation of mass drug treatment with ivermectin in 2009. This fulfillment of the criteria for cessation of mass distribution of ivermectin in the only known endemic zone of onchocerciasis in Ecuador moves the country into the surveillance phase of official verification for national elimination of transmission of infection. These findings indicate that ivermectin given twice a year with greater than 85% of the community can move a program to the final stages of verification of transmission interruption.
Full Text Available Abstract Background Anti-Wolbachia treatment with doxycycline is effective in sterilising and killing adult Onchocerca volvulus nematodes, proving superior to ivermectin and of great potential as an alternative approach for the treatment and control of onchocerciasis, particularly in areas of Loa loa co-endemicity. Nevertheless, the length of the required treatment poses potential logistical problems and risk of poor compliance, raising a barrier to the use of doxycycline in Mass Drug Administration (MDA strategies. In 2007 and 2008 a feasibility trial of community-directed treatment with doxycycline was carried out in two health districts in Cameroon, co-endemic for O. volvulus and L. loa. With 17,519 eligible subjects, the therapeutic coverage was 73.8% with 97.5% compliance, encouraging the feasibility of using doxycycline community-directed delivery in restricted populations of this size. The current study evaluated the effectiveness of this community-directed delivery of doxycycline four years after delivery. Findings Infection with O. volvulus was evaluated by skin biopsy and nodule palpation. Of the 507 subjects recruited, 375 had completed the treatment with doxycycline followed by one or two rounds of annual ivermectin MDA and 132 received one or two rounds of annual ivermectin MDA alone. Statistically significant lower microfilarial prevalence (17.0% [doxycycline plus ivermectin group], 27.0% [ivermectin only group], p = 0.014 and load (p = 0.012 were found in people that had received doxycycline followed by ivermectin compared to those who received ivermectin only. Conclusions This study demonstrates the long-term effectiveness of doxycycline treatment delivered with a community-directed strategy even when evaluated four years after delivery in an area of ongoing transmission. This finding shows that a multi-week course of treatment is not a barrier to community-delivery of MDA in restricted populations of this size and supports its
Hugo C Turner
Full Text Available It has been proposed that switching from annual to biannual (twice yearly mass community-directed treatment with ivermectin (CDTI might improve the chances of onchocerciasis elimination in some African foci. However, historically, relatively few communities have received biannual treatments in Africa, and there are no cost data associated with increasing ivermectin treatment frequency at a large scale. Collecting cost data is essential for conducting economic evaluations of control programmes. Some countries, such as Ghana, have adopted a biannual treatment strategy in selected districts. We undertook a study to estimate the costs associated with annual and biannual CDTI in Ghana.The study was conducted in the Brong-Ahafo and Northern regions of Ghana. Data collection was organized at the national, regional, district, sub-district and community levels, and involved interviewing key personnel and scrutinizing national records. Data were collected in four districts; one in which treatment is delivered annually, two in which it is delivered biannually, and one where treatment takes place biannually in some communities and annually in others. Both financial and economic costs were collected from the health care provider's perspective.The estimated cost of treating annually was US Dollars (USD 0.45 per person including the value of time donated by the community drug distributors (which was estimated at USD 0.05 per person per treatment round. The cost of CDTI was approximately 50-60% higher in those districts where treatment was biannual than in those where it was annual. Large-scale mass biannual treatment was reported as being well received and considered sustainable.This study provides rigorous evidence of the different costs associated with annual and biannual CDTI in Ghana which can be used to inform an economic evaluation of the debate on the optimal treatment frequency required to control (or eliminate onchocerciasis in Africa.
Turner, Hugo C; Osei-Atweneboana, Mike Y; Walker, Martin; Tettevi, Edward J; Churcher, Thomas S; Asiedu, Odame; Biritwum, Nana-Kwadwo; Basáñez, María-Gloria
It has been proposed that switching from annual to biannual (twice yearly) mass community-directed treatment with ivermectin (CDTI) might improve the chances of onchocerciasis elimination in some African foci. However, historically, relatively few communities have received biannual treatments in Africa, and there are no cost data associated with increasing ivermectin treatment frequency at a large scale. Collecting cost data is essential for conducting economic evaluations of control programmes. Some countries, such as Ghana, have adopted a biannual treatment strategy in selected districts. We undertook a study to estimate the costs associated with annual and biannual CDTI in Ghana. The study was conducted in the Brong-Ahafo and Northern regions of Ghana. Data collection was organized at the national, regional, district, sub-district and community levels, and involved interviewing key personnel and scrutinizing national records. Data were collected in four districts; one in which treatment is delivered annually, two in which it is delivered biannually, and one where treatment takes place biannually in some communities and annually in others. Both financial and economic costs were collected from the health care provider's perspective. The estimated cost of treating annually was US Dollars (USD) 0.45 per person including the value of time donated by the community drug distributors (which was estimated at USD 0.05 per person per treatment round). The cost of CDTI was approximately 50-60% higher in those districts where treatment was biannual than in those where it was annual. Large-scale mass biannual treatment was reported as being well received and considered sustainable. This study provides rigorous evidence of the different costs associated with annual and biannual CDTI in Ghana which can be used to inform an economic evaluation of the debate on the optimal treatment frequency required to control (or eliminate) onchocerciasis in Africa.
Turner, Hugo C.; Osei-Atweneboana, Mike Y.; Walker, Martin; Tettevi, Edward J.; Churcher, Thomas S.; Asiedu, Odame; Biritwum, Nana-Kwadwo; Basáñez, María-Gloria
Background It has been proposed that switching from annual to biannual (twice yearly) mass community-directed treatment with ivermectin (CDTI) might improve the chances of onchocerciasis elimination in some African foci. However, historically, relatively few communities have received biannual treatments in Africa, and there are no cost data associated with increasing ivermectin treatment frequency at a large scale. Collecting cost data is essential for conducting economic evaluations of control programmes. Some countries, such as Ghana, have adopted a biannual treatment strategy in selected districts. We undertook a study to estimate the costs associated with annual and biannual CDTI in Ghana. Methodology The study was conducted in the Brong-Ahafo and Northern regions of Ghana. Data collection was organized at the national, regional, district, sub-district and community levels, and involved interviewing key personnel and scrutinizing national records. Data were collected in four districts; one in which treatment is delivered annually, two in which it is delivered biannually, and one where treatment takes place biannually in some communities and annually in others. Both financial and economic costs were collected from the health care provider's perspective. Principal Findings The estimated cost of treating annually was US Dollars (USD) 0.45 per person including the value of time donated by the community drug distributors (which was estimated at USD 0.05 per person per treatment round). The cost of CDTI was approximately 50–60% higher in those districts where treatment was biannual than in those where it was annual. Large-scale mass biannual treatment was reported as being well received and considered sustainable. Conclusions/Significance This study provides rigorous evidence of the different costs associated with annual and biannual CDTI in Ghana which can be used to inform an economic evaluation of the debate on the optimal treatment frequency required to control
Mullen, K; Prost, A
It has been shown in the epidemiological evaluation of onchocerciasis that the method of taking two or more snips per person contains information about the probabilities of false negatives which can be extracted and used to improve the prevalence estimates. Using the method of maximum likelihood, one can obtain expressions for estimating the prevalence, adjusted for the false negatives, and for estimating the proportion of false negatives. The variances of all estimates are also available, making confidence interval estimation possible.
Haselow, Nancy J; Akame, Julie; Evini, Cyrille; Akongo, Serge
In areas co-endemic for loiasis and onchocerciasis, the classic Community-Directed Treatment using ivermectin (Mectizan(R)) must be adapted as additional program activities, better communication and tighter control of ivermectin stocks are required to minimize risk and manage serious adverse events following ivermectin treatment in patients co-infected with Loa loa. The importance of these serious adverse events on community participation in onchocerciasis control efforts has not been adequately studied. Program implementers do not as of yet fully understand the psychological impact of serious adverse events on communities and therefore have not designed communication strategies that adequately address the real concerns of community members. It is clear, however, that along with an effective case detection and management strategy, a reinforced communication strategy will be required to motivate at least 65% of the total population in onchocerciasis and loiasis co-endemic areas to participate in the treatment program and to take ivermectin over an extended period. This strategy must be based on research undertaken at the community level in order to address the concerns, fears and issues associated with adverse events due to ivermectin - to ensure that communities believe that the benefits of taking ivermectin outweigh the risks. In addition to an overall increase in the time required to sustain onchocerciasis control programs in co-endemic areas, each aspect of the reinforced program and communication strategy - rapid epidemiological assessments, materials development, training, advocacy, community sensitization and mobilization, case management and counselling, supervision, monitoring and evaluation will require additional resources and support from all stakeholders concerned.
Gustavsen, Kenneth; Sodahlon, Yao; Bush, Simon
Diseases don't respect borders, so efforts to control and eliminate diseases must also be flexible and adaptable enough to effectively reach the populations that live in the areas around national frontiers. Onchocerciasis, commonly known as river blindness is a tropical disease that has historically affected millions of people in 35 countries in Africa and Latin America. In Africa, programs and partnerships to address river blindness through mass drug administration have been active for more than 25 years. While in many cases the disease is found in isolated foci that fall entirely within national boundaries, the geographic scope of many affected areas crosses country borders. National river blindness programs are the responsibility of each nation's Ministry of Health, so in cross-border situations there is a need for effective country-country collaboration. Cross-border collaboration for onchocerciasis control efforts in the countries of the Mano River Basin illustrates the positive impact of a creative model, and offers lessons for expanded application for onchocerciasis elimination as well as other neglected tropical disease (NTD) control and elimination programs.
Soboslay, P T; Dreweck, C M; Hoffmann, W H; Lüder, C G; Heuschkel, C; Görgen, H; Banla, M; Schulz-Key, H
A longitudinal investigation has been conducted into the cell-mediated immune responses of onchocerciasis patients after a single-dose treatment with ivermectin. Untreated patients tested for delayed cutaneous hypersensitivity (DCH) to seven recall antigens showed lower responses than infection-free control individuals (P less than 0.01), but 6 and 14 months after treatment DCH reactions increased to similar levels to those seen in the controls. The in vitro cellular reactivity to Onchocerca volvulus-derived antigen (OvAg) was reduced in untreated patients as compared with controls, and the lymphocyte blastogenic responses to OvAg and streptolysin-O clearly improved up to 14 months after treatment. Peripheral blood mononuclear cells (PBMC) from untreated patients produced IL-1 beta, tumour necrosis factor-alpha (TNF-alpha) and IL-6 in response to mitogenic stimulation with phytohaemagglutinin (PHA), only low levels of IL-1 beta, IL-2 and TNF-alpha in response to OvAg, but higher amounts of IL-4 and interferon-gamma (IFN-gamma) in response to OvAg than control individuals. After ivermectin treatment, the OvAg-induced production of IL-1 beta and TNF-alpha increased significantly 1 and 14 months after treatment. The PHA-induced production of IL-2 and IL-4 increased 1 month after treatment and remained significantly elevated until 14 months after treatment, whereas the OvAg-specific secretion of IL-2, IL-4 and IFN-gamma did not change after ivermectin treatment. Flow cytometric analysis of lymphocyte-subsets in the peripheral blood of untreated patients revealed a relative and absolute (P less than 0.01) diminution of CD4+ cells and a significantly smaller CD4+/CD8+ cell ratio as compared with controls. By 4 weeks after treatment and thereafter, CD4+ T cells increased relatively and absolutely (P less than 0.01); likewise there was an absolute increase in T-helper-inducer cells (CD4+CD45RO+) and a temporarily improved CD4+/CD8+ cell ratio (P = 0.001). The expression of
Full Text Available Onchocerciasis is an endemic disease in Ondo state, Nigeria. Community directed distribution of ivermectin is currently on-going in some local government areas of the state. Randomly selected persons (2 331 males and 2 469 females were interviewed using a modified rapid assessment procedure for Loa loa (RAPLOA to assess community directed treatment with ivermectin. The retrospective study evaluated the coverage, impacts and adverse reactions to the drug treatment. A questionnaire was administered by house-to-house visit in six local government areas, implementing community directed treatment with ivermectin (CDTI in this bioclimatic zone. A total of 2,398 respondents were reported to have participated in the treatment. The overall ivermectin coverage of 49.96% was recorded (range 0 - 52% in different communities. Adverse reactions from ivermectin administration were experienced in 38% of individuals. Diverse adverse reactions experienced included predominantly itching (18.50%; oedema, especially of the face and the limbs (8.2%; rashes (3.4% and body weakness (2.4%. Expulsion of intestinal worms occurred in 0.96% of the respondents. The occurrence of adverse reactions in relation to age categories was statistically significant. Neither fatal nor severe adverse reactions were reported by respondents. Significantly, despite experienced adverse reactions, continued participation, acceptability and compliance to ivermectin treatment was expressed by the various communities. This attitude is in consonance with the African Programme for Onchocerciasis Control (APOC objectives. Rev. Biol. Trop. 56 (4: 1635-1643. Epub 2008 December 12.La oncocercosis es endémica en el estado Ondo, Nigeria. Se seleccionaron 4 800 personas al azar para evaluar con encuesta retrospectiva la cobertura, efectos y reacciones al tratamiento farmacológico con ivermectina administrado por la misma comunidad. La cobertura global de ivermectina fue 50 % con reacciones adversas en
Dadzie, K Y; Bird, A C; Awadzi, K; Schulz-Key, H; Gilles, H M; Aziz, M A
The effect of ivermectin, a new microfilaricide, was assessed in a double blind trial against diethylcarbamazine citrate (DEC) and placebo. Fifty-nine adult males with moderate to heavy infection with Onchocerca volvulus and with eye involvement were recruited from an area under Onchocerciasis Control Programme (OCP) vector control in Northern Ghana. They were randomly assigned to an eight-day treatment with ivermectin as a single dose of 12 mg on day 1 followed by placebo for the remaining seven days, or DEC, total dose 1.3 g, or placebo, and ophthalmological review was undertaken over a period of one year. DEC acted quickly to eliminate microfilariae from the eye and was associated with reactive ocular changes and in a few cases functional deficit. Ivermectin eliminated microfilariae slowly from the anterior chamber of the eye over a period of six months. The ocular inflammatory reaction was minimal and no functional deficit occurred. It is postulated that the observed slow action of ivermectin on the eye may be attributed in part to its instability to cross the blood-aqueous humour barrier because of its molecular size as a macrocyclic lactone causing microfilariae to leave the eye gradually along a newly created gradient. Ivermectin is an effective microfilaricide with minimal ocular adverse effect and could therefore be suitable for widespread application without strict supervision. PMID:3548811
Full Text Available Japan is a country of high specific diversity of Onchocerca with eight species, the adults of two not yet known. Onchocerca dewittei japonica, a common filarial parasite of wild boar, had been proved to be the agent of five zoonotic onchocerciasis in Kyushu island with morphological and molecular studies. The sixth case, at Hiroshima in the main island, was identified to the same Onchocerca species, based on adult characters observed on histological sections. To consolidate the identification, mitochondrial cytochrome c oxidase subunit 1 (CO1 gene analysis was attempted with the formalin-fixed, paraffin-embedded parasite specimen. The sequence (196 bp of a CO1 gene fragment of the parasite successfully PCR-amplified agreed well with those of O. dewittei japonica registered in GenBank, confirming the morphological identification. Moreover a comparison with the CO1 gene sequences of six other Onchocerca species in GenBank excluded the possibility that Onchocerca sp. from wild boar and Onchocerca sp. type A from cattle in Japan, were the causative agents in this case. Mitochondrial DNA analysis proved to be a valuable tool to support the morphological method for the discrimination of zoonotic Onchocerca species in a histological specimen.
Wildenburg, G; Darge, K; Knab, J; Tischendorf, F W; Bonow, I; Büttner, D W
Lymph node and skin biopsies from Liberian patients with generalized and localized (sowda) onchocerciasis were studied 12-68 hours after oral administration of ivermectin at a single dose of 150 micrograms/kg body weight. Electron microscopic examination and immunohistochemical staining with antibodies against two different forms of eosinophil cationic protein (ECP EG1, ECP EG2), eosinophil peroxidase (EPO) and cationic leukocyte antigen (CLA) were performed. Following their disappearance from the skin, a large number of microfilariae was found in the regional lymph nodes. The lymph nodes from treated patients had over ten times more eosinophils compared to those from untreated persons with a peak of eosinophil density at 40-48 hours after treatment. Degenerating microfilariae in the lymph nodes were encircled by eosinophils, which showed positive immunostaining for ECP, EPO or CLA. Intra- and extracellular eosinophil granules revealed a great variation in their condition. In some specific granules a variety of structural alterations in the crystalloid cores occurred while in others different stages of deficiency in the matrix electron density were observed. The frequent necrosis of eosinophils in the immediate vicinity and at some distance from the microfilariae, with subsequent release of granules and the deposition of toxic cationic granule proteins onto the microfilarial cuticle during the eosinophil-parasite adherence reaction, demonstrated the function of these proteins in the ivermectin-reinforced killing of microfilariae in lymph nodes.
Moses N. Katabarwa
Full Text Available We followed up the 1996 baseline parasitological and entomological studies on onchocerciasis transmission in eleven health districts in West Region, Cameroon. Annual mass ivermectin treatment had been provided for 15 years. Follow-up assessments which took place in 2005, 2006, and 2011 consisted of skin snips for microfilariae (mf and palpation examinations for nodules. Follow-up Simulium vector dissections for larval infection rates were done from 2011 to 2012. mf prevalence in adults dropped from 68.7% to 11.4%, and nodule prevalence dropped from 65.9% to 12.1%. The decrease of mf prevalence in children from 29.2% to 8.9% was evidence that transmission was still continuing. mf rates in the follow-up assessments among adults and in children levelled out after a sharp reduction from baseline levels. Only three health districts out of 11 were close to interruption of transmission. Evidence of continuing transmission was also observed in two out of three fly collection sites that had infective rates of 0.19% and 0.18% and ATP of 70 (Foumbot and 300 (Massangam, respectively. Therefore, halting of annual mass treatment with ivermectin cannot be done after 15 years as it might escalate the risk of transmission recrudescence.
Full Text Available Four cytotypes of Simulium exiguum occur in Ecuador, where this morphospecies is the primary vector of onchocerciasis. In this paper, we give the first full description of the banding pattern of the larval polytene chromosomes of the Quevedo cytotypes differ from the chromosomal standard sequence (of the Cayapa cytotype by the fixed inversions IIL-5 and IIL-6. The Quevedo cytotype additionally differs from the standard and Bucay cytotypes by processing a differentiated X chromosome, wich is indicated by the inversion IIS-A. As the degree of reproductive isolation between the Bucay and Quevedo cytotypes has not yet been estabilished, they must be regarded as intraspecific variants of the same species. In fact, isoenzyme characterizations showed that the Bucay and Quevedo cytotypes are differentiated only to the extent expected of incipient species or geographical populations. Moreover, the sibiling species status previously given to the Bucay cytotype needs be reassessed, there being inadequate analysis from areas in Ecuador where Bucay occurs in sympatry with the standard Cayapa cytotype. No isoenzyme electromorphs were discovered that identified all or mostadult females of any one (cytotype-pure collection.
This review concerns the efficacy and safety of combinations of various drugs, including albendazole (ALB), diethylcarbamazine (DEC), ivermectin (IVM), mebendazole and praziquantel (PZQ). There were no significant pharmacokinetic interactions when ALB-PZQ, ALB-DEC, ALB-IVM or ALB-IVM-PZQ were co-administered. ALB did not add to the cure rate of PZQ in the treatment of Schistosoma japonicum, S. mansoni and S. haematobium. ALB and DEC in combination and alone were ineffective against S. haematobium infections. No combinations (ALB-PZQ, ALB-IVM and ALB-DEC) were superior to ALB against Ascaris lumbricoides and hookworm infections, whilst IVM, but not PZQ or DEC, added to the effect of ALB in the treatment of Trichuris trichiura. Results with ALB added to single-drug therapy with IVM or DEC against lymphatic filariasis were inconclusive, but DEC and IVM in combination appeared to be superior to DEC or IVM alone. None of the drug combinations against lymphatic filariasis showed more adverse reactions than single-drug therapy. In onchocerciasis patients, ALB and IVM were safe in those also infected with lymphatic filariasis, but were not superior to IVM alone. Existing policies are based on limited knowledge. Well conducted, comparative, randomised controlled studies would greatly aid in the future use of these drug combinations.
A comprehensive LANDSAT related resource inventory was performed in parts of Ghana, Benin, and Upper Volta to determine resource development potential in areas freed of the disease onchocerciasis. The ultimate success of the project lies in the effective use of the data by host country personnel in resource development projects. This requires project follow-through, adequate training of regional counterparts, and integration of the data into an easily used framework. Present levels of support systems and technical expertise in West Africa indicate that an automated system for natural resource data is not currently appropriate. Suggestions for the greater implementation of such inventories are explored.
Kelly L. Johnston
Full Text Available Lymphatic filariasis and onchocerciasis are debilitating diseases caused by parasitic filarial nematodes infecting around 150 million people throughout the tropics with more than 1.5 billion at risk. As with other neglected tropical diseases, classical drug-discovery and development is lacking and a 50 year programme of macrofilaricidal discovery failed to deliver a drug which can be used as a public health tool. Recently, antibiotic targeting of filarial Wolbachia, an essential bacterial symbiont, has provided a novel drug treatment for filariasis with macrofilaricidal activity, although the current gold-standard, doxycycline, is unsuitable for use in mass drug administration (MDA. The anti-Wolbachia (A·WOL Consortium aims to identify novel anti-Wolbachia drugs, compounds or combinations that are suitable for use in MDA. Development of a Wolbachia cell-based assay has enabled the screening of the approved human drug-pharmacopoeia (∼2600 drugs for a potential repurposing. This screening strategy has revealed that approved drugs from various classes show significant bacterial load reduction equal to or superior to the gold-standard doxycycline, with 69 orally available hits from different drug categories being identified. Based on our defined hit criteria, 15 compounds were then selectively screened in a Litomosoides sigmodontis mouse model, 4 of which were active. These came from the tetracycline, fluoroquinolone and rifamycin classes. This strategy of repurposing approved drugs is a promising development in the goal of finding a novel treatment against filariasis and could also be a strategy applicable for other neglected tropical diseases.
Joseph Oghenebukome Onojafe
Full Text Available Objective: To determine the ecological parameters affecting the distribution of Simulium damnosum immature stages in some rivers within the endemic areas of Delta State, Nigeria. Methods: Onchocerca larvae were observed and identified for each river. An average sized colander with fine mesh was used to scoop the area to obtain the larvae along with other benthos. Physiochemical characteristics of the water at breeding sites were analyzed for a 12 months period. Correlation analysis was performed to establish the association between the larval densities and physicochemical parameters of blackfly. Results: The seasonal variation in the physical and chemical characteristics of these environments impaired the population dynamics of blackflies. The physicochemical parameters significantly varied among breeding sites (P < 0.05, in which the temperature of surface water ranged between 23.2 °C and 30.3 °C, water flow velocity ranged between 0.4 and 1.3 m/s, dissolved oxygen ranged between 5.1 and 9.0 mg/L and pH ranged between 5.4 and 7.4. The mean collection of Simulium larvae was the highest in River Otor (44.1 and the least in River Namormai (19.1. There was significant difference (P < 0.05 in the number of larvae collected from the sampled rivers. Also, the number of larvae collected significantly correlated with surface water temperature, water flow velocity, dissolved oxygen and pH. Conclusions: This study identified significant correlations between physicochemical parameters and blackfly larvae densities thus providing a precontrol evidence-based data for the control of onchocerciasis in the endemic areas of North Delta.
Full Text Available The future dispersal of onchocerciasis in Ecuador is dependent on the distribution of cytotypes of the vector species complex Simulium exiguum. Over the last 14 years, collections of larvae have been made from over 25 rivers, between 80-1600 m altitude, from various sites on both sides of the Andes. Analysis of larval polytene chromosomes was used to determine the distributions of each cytotype. On the western side of the Andes, the Cayapa cytotype (the only cytotype directly incriminated as a vector has a distribution from Santo Domingo de los Colorados northwards. The Quevedo and Bucay cytotypes occur from Santo Domingo de los Colorados southwards. On the eastern side of the Andes, the Aguarico cytotype occurs in the Rio Aguarico and a new cytotype is present in the tributaries of the Rio Napo. Whether the disease will spread south of Santo Domingo and on the eastern side of the Andes depends on vector capacity of the cytotypes and the dispersal patterns of individuals infected with onchocerciasis. At present the Aguarico, Bucay and Quevedo cytotypes are known to be efficient hosts, but their biting preferences and biting densities have not yet been evaluated
Grillet, M E; Basáñez, M G; Vivas-Martínez, S; Villamizar, N; Frontado, H; Cortez, J; Coronel, P; Botto, C
We investigated some entomological factors underlying altitudinal prevalence variation in the Venezuelan Amazonia human onchocerciasis focus. Spatial and temporal variation in relative abundance, daily biting rate, proportion of parous flies, and monthly parous biting rate were studied for the three main simuliid vectors (based on their vectorial competence: Simulium oyapockense s.l. Floch & Abonnenc approximately = S. incrustatum Lutz variables included monthly rainfall and maximum river height. Simuliid species composition itself varied along the altitudinal and prevalence gradient. S. oyapockense s.l. prevailed below 150 m. Above this altitude and up to 240 m, S. incrustatum and S. guianense s.l. became more frequently and evenly collected along A but not along B, where S. incrustatum remained absent. The daily biting rate of S. oyapockense s.l. was higher during the dry season along A, whereas the converse took place along B. Daily biting rate of S. incrustatum was lowest during early rains. By contrast, the daily biting rate of S. guianense s.l. was highest during this period. There was a significant negative cross-correlation between proportion of parous of S. oyapockense s.l. and river height (2 and 3 mo lagged), whereas this variable (1 and 2 mo lagged) was positively correlated with the proportion of parous flies for S. incrustatum. Monthly parous biting rate values suggest that the months contributing most to onchocerciasis transmission in the area are likely to be the dry season and the transition periods between seasons.
Lakwo, T L; Garms, R; Rubaale, T; Katabarwa, M; Walsh, F; Habomugisha, P; Oguttu, D; Unnasch, T; Namanya, H; Tukesiga, E; Katamanywa, J; Bamuhiiga, J; Byamukama, E; Agunyo, S; Richards, F
The Itwara onchocerciasis focus is located around the Itwara forest reserve in western Uganda. In 1991, annual treatments with ivermectin started in the focus. They were supplemented in 1995 by the control of the vector Simulium neavei, which was subsequently eliminated from the focus. The impact of the two interventions on the disease was assessed in 2010 by nodule palpations, examinations of skin snips by microscopy and PCR, and Ov16 recombinant ELISA. There was no evidence of any microfilaria in 688 skin snips and only 2 (0.06%) of 3316 children examined for IgG4 were slightly above the arbitrary cut off of 40. A follow up of the same children 21 months later in 2012 confirmed that both were negative for diagnostic antigen Ov-16, skin snip microscopy and PCR. Based on the World Health Organization (WHO) elimination criteria of 2001 and the Uganda onchocerciasis certification guidelines, it was concluded that the disease has disappeared from the Itwara focus after 19 years of ivermectin treatments and the elimination of the vector around 2001. Ivermectin treatments were recommended to be halted.
Treatment of co-infection with bancroftian filariasis and onchocerciasis: a safety and efficacy study of albendazole with ivermectin compared to treatment of single infection with bancroftian filariasis
Makunde, William H; Kamugisha, Leo M; Massaga, Julius J; Makunde, Rachel W; Savael, Zakana X; Akida, Juma; Salum, Fred M; Taylor, Mark J
Background In order to use a combination of ivermectin and albendazole for the elimination of lymphatic filariasis, it is important to assess the potential risk of increased adverse events in individuals infected with both lymphatic filariasis and onchocerciasis. We compared the safety and efficacy of albendazole (400 mg) in combination with ivermectin (150 micrograms/kg), for the treatment of co-infections of Wuchereria bancrofti and Onchocerca volvulus with single infection of W. bancrofti. Methods The safety study on co-infections was a crossover, double blind design, while for the single infection of bancroftian filariasis an open design comparing two treatments was used. For co-infection, one group was allocated a single dose of ivermectin (150 micrograms/kg) plus albendazole (400 mg) (Group A). The other group received placebo (Group B). Five days later the treatment regime was reversed, with the Group A receiving placebo and Group B receiving treatment. For the single bancroftian filariasis infection, one group received a single dose of albendazole (400 mg) plus ivermectin (150 μg/kg) (Group C) while the other group received a single dose of albendazole (400 mg) alone (Group D). Blood and skin specimens were collected on admission day, day 0, and on days 2, 3, and 7 to assess drug safety and efficacy. Thereafter, blood and skin specimens were collected during the 12 months follow up for the assessment of drug efficacy. Study individuals were clinically monitored every six hours during the first 48 hours following treatment, and routine clinical examinations were performed during the hospitalisation period and follow-up. Results In individuals co-infected with bancroftian filariasis and onchocerciasis, treatment with ivermectin and albendazole was safe and tolerable. Physiological indices showed no differences between groups with co-infection (W. bancrofti and O. volvulus) or single infection (W. bancrofti). The frequency of adverse events in co
Full Text Available To evaluate the effect of ivermectin mass drug administration on strongyloidiasis and other soil transmitted helminthiases.We conducted a retrospective analysis of data collected in Esmeraldas (Ecuador during surveys conducted in areas where ivermectin was annually administered to the entire population for the control of onchocerciasis. Data from 5 surveys, conducted between 1990 (before the start of the distribution of ivermectin and 2013 (six years after the interruption of the intervention were analyzed. The surveys also comprised areas where ivermectin was not distributed because onchocerciasis was not endemic. Different laboratory techniques were used in the different surveys (direct fecal smear, formol-ether concentration, IFAT and IVD ELISA for Strongyloides stercoralis.In the areas where ivermectin was distributed the strongyloidiasis prevalence fell from 6.8% in 1990 to zero in 1996 and 1999. In 2013 prevalence in children was zero with stool examination and 1.3% with serology, in adult 0.7% and 2.7%. In areas not covered by ivermectin distribution the prevalence was 23.5% and 16.1% in 1996 and 1999, respectively. In 2013 the prevalence was 0.6% with fecal exam and 9.3% with serology in children and 2.3% and 17.9% in adults. Regarding other soil transmitted helminthiases: in areas where ivermectin was distributed the prevalence of T. trichiura was significantly reduced, while A. lumbricoides and hookworms were seemingly unaffected.Periodic mass distribution of ivermectin had a significant impact on the prevalence of strongyloidiasis, less on trichuriasis and apparently no effect on ascariasis and hookworm infections.
Anselmi, Mariella; Buonfrate, Dora; Guevara Espinoza, Angel; Prandi, Rosanna; Marquez, Monica; Gobbo, Maria; Montresor, Antonio; Albonico, Marco; Racines Orbe, Marcia; Bisoffi, Zeno
Objectives To evaluate the effect of ivermectin mass drug administration on strongyloidiasis and other soil transmitted helminthiases. Methods We conducted a retrospective analysis of data collected in Esmeraldas (Ecuador) during surveys conducted in areas where ivermectin was annually administered to the entire population for the control of onchocerciasis. Data from 5 surveys, conducted between 1990 (before the start of the distribution of ivermectin) and 2013 (six years after the interruption of the intervention) were analyzed. The surveys also comprised areas where ivermectin was not distributed because onchocerciasis was not endemic. Different laboratory techniques were used in the different surveys (direct fecal smear, formol-ether concentration, IFAT and IVD ELISA for Strongyloides stercoralis). Results In the areas where ivermectin was distributed the strongyloidiasis prevalence fell from 6.8% in 1990 to zero in 1996 and 1999. In 2013 prevalence in children was zero with stool examination and 1.3% with serology, in adult 0.7% and 2.7%. In areas not covered by ivermectin distribution the prevalence was 23.5% and 16.1% in 1996 and 1999, respectively. In 2013 the prevalence was 0.6% with fecal exam and 9.3% with serology in children and 2.3% and 17.9% in adults. Regarding other soil transmitted helminthiases: in areas where ivermectin was distributed the prevalence of T. trichiura was significantly reduced, while A. lumbricoides and hookworms were seemingly unaffected. Conclusions Periodic mass distribution of ivermectin had a significant impact on the prevalence of strongyloidiasis, less on trichuriasis and apparently no effect on ascariasis and hookworm infections. PMID:26540412
Joseph B Koroma
Full Text Available BACKGROUND: 1974-2005 studies across Sierra Leone showed onchocerciasis endemicity in 12 of 14 health districts (HDs and baseline studies 2005-2008 showed lymphatic filariasis (LF endemicity in all 14 HDs. Three integrated annual mass drug administration (MDA were conducted in the 12 co-endemic districts 2008-2010 with good geographic, programme and drug coverage. Midterm assessment was conducted 2011 to determine impact of these MDAs on LF in these districts. METHODOLOGY/PRINCIPAL FINDINGS: The mf prevalence and intensity in the 12 districts were determined using the thick blood film method and results compared with baseline data from 2007-2008. Overall mf prevalence fell from 2.6% (95% CI: 2.3%-3.0% to 0.3% (95% CI: 0.19%-0.47%, a decrease of 88.5% (p = 0.000; prevalence was 0.0% (100.0% decrease in four districts: Bo, Moyamba, Kenema and Kono (p = 0.001, 0.025, 0.085 and 0.000 respectively; and seven districts had reductions in mf prevalence of between 70.0% and 95.0% (p = 0.000, 0.060, 0.001, 0.014, 0.000, 0.000 and 0.002 for Bombali, Bonthe, Kailahun, Kambia, Koinadugu, Port Loko and Tonkolili districts respectively. Pujehun had baseline mf prevalence of 0.0%, which was maintained. Only Bombali still had an mf prevalence ≥1.0% (1.58%, 95% CI: 0.80%-3.09%, and this is the district that had the highest baseline mf prevalence: 6.9% (95% CI: 5.3%-8.8%. Overall arithmetic mean mf density after three MDAs was 17.59 mf/ml (95% CI: 15.64 mf/ml-19.55 mf/ml among mf positive individuals (65.4% decrease from baseline of 50.9 mf/ml (95% CI: 40.25 mf/ml-61.62 mf/ml; p = 0.001 and 0.05 mf/ml (95% CI: 0.03 mf/ml-0.08 mf/ml for the entire population examined (96.2% decrease from baseline of 1.32 mf/ml (95% CI: 1.00 mf/ml-1.65 mf/ml; p = 0.000. CONCLUSIONS/SIGNIFICANCE: The results show that mf prevalence decreased to <1.0% in all but one of the 12 districts after three MDAs. Overall mf density reduced by 65.0% among mf
... 6 countries in the Americas (Mexico, Guatemala, Ecuador, Colombia, Venezuela, and Brazil), but transmission has now stopped ... infection is greater in adventure travelers, missionaries, and Peace Corps and other long-term volunteers who are ...
New molecular identifiers for Simulium limbatum and Simulium incrustatum s.l. and the detection of genetic substructure with potential implications for onchocerciasis epidemiology in the Amazonia focus of Brazil.
Conceição, Priscila A; Crainey, James L; Almeida, Tatiana P; Shelley, Anthony J; Luz, Sergio L B
The Amazonia onchocerciasis focus of southern Venezuela and northern Brazil is the larger of the two remaining Latin American onchocerciasis foci where disease transmission still occurs and is often regarded as the most challenging of all the Latin American foci to eliminate onchocerciasis. The site is home to a population of over 20,000 semi-nomadic, hunter-gatherer Yanomami people and is made-up of a mosaic of rainforest and savannah ecologies, which are influenced by the area's undulating terrain and rich geological diversity. At least six blackfly vectors have been implicated in onchocerciasis transmission in this focus; however, because of the difficulty in their routine identification the relative importance of each has been obscured. Simulium limbatum and Simulium incrustatum s.l. have both been recorded as vectors in the Amazonia focus, but they are difficult to discriminate morphologically and thus the ecological range of these species, and indeed the presence of S. limbatum in the Amazonia focus at all, have remained controversial. In the work described here, we report 15 S. incrustatum s.l. CO1 sequences and 27 S. limbatum sequences obtained from field-caught adult female blackflies collected from forest and savannah localities, inside and just outside the Amazonia focus. Phylogenetic analysis with the sequences generated in this study, showed that both the S. limbatum and the S. incrustatum s.l. CO1 sequences obtained (even from specimens living in sympatry) all fell into discrete species-specific bootstrap-supported monophyletic groups and thus confirmed the utility of the CO1 gene for identifying both these species inside the Amazonia focus. As the S. limbatum-exclusive cluster included CO1 sequences obtained from forest-caught and morphologically identified specimens these results provide the clearest evidence yet of the presence of S. limbatum inside the Amazonia focus. The question, however, of whether S. limbatum is actually a vector in the focus
Lont, Yvonne L; Coffeng, Luc E; de Vlas, Sake J; Golden, Allison; de Los Santos, Tala; Domingo, Gonzalo J; Stolk, Wilma A
Onchocerciasis is targeted for elimination in Africa through annual or biannual ivermectin mass drug administration (MDA). An immunodiagnostic test, based on the detection of human IgG4 antibodies in the blood to the Onchocerca volvulus-specific antigen Ov16, is one of the recommended tools for determining whether transmission is interrupted and mass treatment can stop. For different transmission settings, the relationship between post-MDA Ov16 antibody prevalence in children (measured 1 year after the last round of MDA) and the duration and coverage of MDA, the mf prevalence in the population, and the probability that onchocerciasis is eventually eliminated is explored through mathematical modelling. The ONCHOSIM model was extended with new output on the Ov16 antibody serostatus of individuals. Seroconversion was assumed to be triggered by the first worm establishing in the host, with seroconversion occurring either before maturation, after maturation or only after the start of mf production. We are mainly interested in seroconversion rates in children, and for now ignore the possibility of seroreversion to simplify the model. Yearly repeated MDA leads to a strong reduction in the parasite acquisition rate in humans. This reduces the seroconversion rate in newborns and young children, while those who seroconverted before the start of control remain antibody positive. Both the microfiladermia prevalence in the population aged 5 years and above and the Ov16 antibody prevalence in children under 10 declined with increasing duration of MDA. The association between either of these indicators and the model-predicted probability of elimination was not influenced much by the assumed treatment coverage levels, but was found to depend on baseline endemicity levels, assumptions regarding the trigger of seroconversion, and diagnostic test characteristics (sensitivity and specificity). Better understanding of the dynamics of Ov16 antibody responses is required for accurate
Batsa, Linda; Ayisi-Boateng, Nana Kwame; Osei-Mensah, Jubin; Mubarik, Yusif; Konadu, Peter; Ricchiuto, Arcangelo; Fimmers, Rolf; Arriens, Sandra; Dubben, Bettina; Ford, Louise; Taylor, Mark; Hoerauf, Achim
The search for new macrofilaricidal drugs against onchocerciasis that can be administered in shorter regimens than required for doxycycline (DOX, 200mg/d given for 4–6 weeks), identified minocycline (MIN) with superior efficacy to DOX. Further reduction in the treatment regimen may be achieved with co-administration with standard anti-filarial drugs. Therefore a randomized, open-label, pilot trial was carried out in an area in Ghana endemic for onchocerciasis, comprising 5 different regimens: the standard regimen DOX 200mg/d for 4 weeks (DOX 4w, N = 33), the experimental regimens MIN 200mg/d for 3 weeks (MIN 3w; N = 30), DOX 200mg/d for 3 weeks plus albendazole (ALB) 800mg/d for 3 days (DOX 3w + ALB 3d, N = 32), DOX 200mg/d for 3 weeks (DOX 3w, N = 31) and ALB 800mg for 3 days (ALB 3d, N = 30). Out of 158 randomized participants, 116 (74.4%) were present for the follow-up at 6 months of whom 99 participants (63.5%) followed the treatment per protocol and underwent surgery. Histological analysis of the adult worms in the extirpated nodules revealed absence of Wolbachia in 98.8% (DOX 4w), 81.4% (DOX 3w + ALB 3d), 72.7% (MIN 3w), 64.1% (DOX 3w) and 35.2% (ALB 3d) of the female worms. All 4 treatment regimens showed superiority to ALB 3d (p < 0.001, p < 0.001, p = 0.002, p = 0.008, respectively), which was confirmed by real-time PCR. Additionally, DOX 4w showed superiority to all other treatment arms. Furthermore DOX 4w and DOX 3w + ALB 3d showed a higher amount of female worms with degenerated embryogenesis compared to ALB 3d (p = 0.028, p = 0.042, respectively). These results confirm earlier studies that DOX 4w is sufficient for Wolbachia depletion and the desired parasitological effects. The data further suggest that there is an additive effect of ALB (3 days) on top of that of DOX alone, and that MIN shows a trend for stronger potency than DOX. These latter two results are preliminary and need confirmation in a fully randomized controlled phase 2 trial. Trial
Takaoka, H; Bain, O; Uni, S; Korenaga, M; Kozek, W J; Shirasaka, C; Aoki, C; Otsuka, Y; Fukuda, M; Eshita, Y; Daa, T
Histological examination of a nodule removed from the back of the hand of a 58-year-old woman from Oita, Kyushu, Japan showed an Onchocerca female sectioned through the posterior region of the worm (ovaries identifiable) and young (thin cuticle). Six Onchocerca species are enzootic in that area: O. gutturosa and O. lienalis in cattle, O. suzukii in serows (Capricornis crispus), O. skrjabini and an Onchocerca sp. in Cervus nippon nippon, and O. dewittei japonica in wild boar (Sus scrofa leucomystax). Diagnostic characters of female Onchocerca species, such as the cuticle and its ridges, change along the body length. Tables of the histologic morphology of the mid- and posterior body-regions of the local species are presented. In addition, it was observed that transverse ridges arose and thickened during the adult stage (examination of fourth stage and juvenile females of O. volvulus). The specimen described in this report, with its prominent and widely spaced ridges, was identified as O. d. japonica. Four of the 10 zoonotic cases of onchocerciasis reported worldwide were from Oita, three of them being caused by O. d. japonica, the prevalence of which in local wild boar was 22 of 24 (92%).
Crainey, James L; Mattos-Glória, Aline; Hamada, Neusa; Luz, Sérgio L B
Following the success of the Onchocerciasis Elimination Programme for the Americas (OEPA), there is now just one Latin American onchocerciasis focus where onchocerciasis transmission is described as 'on-going:' the Amazonia Onchocerciasis focus. In the hyperendemic highland areas of the Amazonia focus, Simulium guianense s.l. Wise are the most important vectors of the disease. Populations of S. guianense s.l. are, however, known to vary in their cytogenetics and in a range of behaviours, including in their biting habits. In the hypoendemic lowland areas of the Amazonia focus, for example, S. guianense s.l. are generally regarded as zoophilic and consequently unimportant to disease transmission. Robust tools, to discriminate among various populations of S. guianense s.l. have, however, not yet been developed. In the work reported here, we have assessed the utility of a ribosomal DNA sequence fragment spanning the nuclear ribosomal ITS-1, ITS-2 and 5.8S sequence regions and a ∼850 nucleotide portion of the mitochondrial cytochrome oxidase gene (CO1) for species-level identification and for resolving the within species substructuring. We report here how we have generated 78 CO1 sequences from a rich set of both zoophilic and anthropophilic populations of S. guianense s.l. that were collected from eight sites that are broadly distributed across Brazil. Consistent with previous findings, our analysis supports the genetic isolation of Simulium litobranchium from S. guianense s.l. In contrast with previous findings, however, our results did not provide support for the divergence of the two species prior to the radiation of S. guianense s.l. In our analysis of the S. guianense s.l. ribosomal DNA sequence trace files we generated, we provide clear evidence of multiple within-specimen single nucleotide polymorphisms and indels suggesting that S. guianense s.l. ribosomal DNA is not a good target for conventional DNA barcoding. This is the first report of S. guianense s
Jones, B R; Anderson, J; Fuglsang, H
Diethylcarbamazine was given as eye drops in varying concentrations in a half-log dilution series from 1.0 to 0.0001% to patients with ocular onchocerciasis. Migration of microfilariae into the cornea, followed by their straightening and disintegration, was observed with delivery rates as low as 0.1 microgram/hour. Dose-related adverse inflammatory reactions, including the development of globular limbal infiltrates with itching and redness, were seen with delivery rates as low as 0.6 microgram/hour, but substantial inflammatory reactions, including severe vasculitis, were seen only with delivery rates of or above 1.0 microgram/hour. This suggests that it should be possible to achieve beneficial clearing of the microfilarial load, without adverse reactions, by continuous non-pulsed delivery of the drug. Technology exists for such delivery, either directly into the eye or systemically by a transdermal system that could give 3 to 7 days' treatment from each application. The observations reported suggest that after preliminary clearing of the microfilarial load by carefully controlled delivery of DEC it may be possible to maintain therapy by less strictly controlled delivery in DEC-medicated salt, or to use treatment with suramin, without incurring substantial adverse reactions, such as a deterioration in vision in cases in which the optic nerve is already compromised. Continuous non-pulsed DEC delivery systems could have a place in the management of onchocercal sclerosing keratitis. The unique opportunities for using the ocular model to define the requirements for beneficial non-damaging therapy with DEC should be explored in further field trials. Images PMID:678494
Ortega Gutiérrez, M; Ramírez, A; Miranda, R
In this research we tried to demonstrate differences in transmission intensities of onchocerciasis by Simulium ochraceum in the community of Golondrinas, Municipality of Acacoyagua in the Soconusco area of the state of Chiapas. Adult females of this species were captured in the center of the villages, the coffee plantation, and the corn bean planted plots, during 7 to 10 consecutive days of the months of June, August, November and December of 1983, and January, March, and May of 1984. Captures were made from 7:00 to 11:00 h, by two persons (a human bait and a collector) in each of the mentioned areas. Variations in densities of S. ochraceum were not statistically significant among the different areas, although there was a predominance in the center of the villages during all the time periods. There was not a statistical significance in the number of oviparous females, although again the center of 50 villages showed the highest percentages (43.5%), as compared to the coffee plantation (37.8%), and the corn-bean plots (33.8%). Regarding the ratio infection: infectivity, only the infective mosquitoes with L3 showed a statistical significance in the three types of areas, being highest in the center of the villages. Transmission potentials were: center of the village 28.5 L3/human/period; coffee plantation, 73 L3/human/period; corn-bean plot, 5.8 L3/human/period. We discuss the possibility that the differences in densities among the various areas might depend on the variations of the breeding sites, mobility or permanence of the individuals during the hours of greater activity of S. ochraceum, and the wind and light local conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
Joseph Oghenebukome Onojafe; Andy Ogochukwu Egwunyenga; Jephtha Christopher Nmor
Objective:To determine the ecological parameters affecting the distribution ofSimulium damnosum immature stages in some rivers within the endemic areas of Delta State, Nigeria. Methods:Onchocerca larvae were observed and identified for each river. An average sized colander with fine mesh was used to scoop the area to obtain the larvae along with other benthos. Physiochemical characteristics of the water at breeding sites were analyzed for a 12 months period. Correlation analysis was performed to establish the association between the larval densities and physicochemical parameters of blackfly. Results:The seasonal variation in the physical and chemical characteristics of these environments impaired the population dynamics of blackflies. The physicochemical parameters significantly varied among breeding sites (P < 0.05), in which the temperature of surface water ranged between 23.2°C and 30.3°C, water flow velocity ranged between 0.4 and 1.3 m/s, dissolved oxygen ranged between 5.1 and 9.0 mg/L and pH ranged between 5.4 and 7.4. The mean collection ofSimulium larvae was the highest in River Otor (44.1) and the least in River Namormai (19.1). There was significant difference (P < 0.05) in the number of larvae collected from the sampled rivers. Also, the number of larvae collected significantly correlated with surface water temperature, water flow velocity, dissolved oxygen and pH. Conclusions: This study identified significant correlations between physicochemical parameters and blackfly larvae densities thus providing a precontrol evidence-based data for the control of onchocerciasis in the endemic areas of North Delta.
Diallo, S; Aziz, M A; Lariviere, M; Diallo, J S; Diop-Mar, I; N'Dir, O; Badiane, S; Py, D; Schulz-Key, H; Gaxotte, P
Ivermectin (MK-933) has been compared with diethylcarbamazine (DEC) and placebo in a double-blind study in 30 adult male Senegalese patients with Onchocerca volvulus infection. 10 patients were randomly assigned to each treatment group. Ivermectin was administered as a single oral dose of 12 mg and DEC as 50 mg daily for two days and 100 mg twice daily for the following six days, total 1.3 g in eight days. Skin O. volvulus microfilaria densities remained near pre-study values in the placebo patients, but decreased rapidly with both active drugs to mean values about 2% of pretreatment (Day 8) and then increased slowly, reaching in 12 months about 4% of pre-treatment (ivermectin) and 18% (DEC). This difference is statistically significant. Clinical adverse reactions were recorded in four ivermectin, ten DEC and three placebo patients. One ivermectin and six DEC patients received steroid treatment for relief of these reactions. Serious adverse ocular changes were not seen in any patients, possibly because of the steroid therapy in the DEC patients. Adult O. volvulus from onchocercal nodules one and six months after treatment showed no effect of either drug on viability. Intra-uterine developing forms of the microfilariae appeared normal in all three treatment groups at the one month examination but deformed and degenerated forms were evident at six months in the ivermectin group but not in the DEC and placebo patients. Ivermectin as a single oral dose appears to be a safer and more effective microfilaricidal drug in human onchocerciasis than DEC in the standard multi-dose regimen.
Jones, B R; Anderson, J; Fuglsang, H
Diethylcarbamazine was given as eye drops in varying concentrations in a half-log dilution series from 1.0 to 0.0001% to patients with ocular onchocerciasis. Migration of microfilariae into the cornea, followed by their straightening and disintegration, was observed with delivery rates as low as 0.1 microgram/hour. Dose-related adverse inflammatory reactions, including the development of globular limbal infiltrates with itching and redness, were seen with delivery rates as low as 0.6 microgram/hour, but substantial inflammatory reactions, including severe vasculitis, were seen only with delivery rates of or above 1.0 microgram/hour. This suggests that it should be possible to achieve beneficial clearing of the microfilarial load, without adverse reactions, by continuous non-pulsed delivery of the drug. Technology exists for such delivery, either directly into the eye or systemically by a transdermal system that could give 3 to 7 days' treatment from each application. The observations reported suggest that after preliminary clearing of the microfilarial load by carefully controlled delivery of DEC it may be possible to maintain therapy by less strictly controlled delivery in DEC-medicated salt, or to use treatment with suramin, without incurring substantial adverse reactions, such as a deterioration in vision in cases in which the optic nerve is already compromised. Continuous non-pulsed DEC delivery systems could have a place in the management of onchocercal sclerosing keratitis. The unique opportunities for using the ocular model to define the requirements for beneficial non-damaging therapy with DEC should be explored in further field trials.
谢铮; Ifeanyi Nsofor; Rachel Tolhurst
目的:了解不同利益相关方对非洲盘尾丝虫病项目(African Programme for Onchocerciasis Control,APOC)的评价,调查该项目在社区实施中的进展及所存在的问题,为未来被忽视的热带病(neglected tropical diseases,NTD)控制项目提供政策建议.方法:采用个人深度访谈和焦点组访谈作为研究方法,使用主题框架法作为资料处理方法.结果:药物发放取得了一定的效果,社区居民普遍认可并接受了发放的预防药物.同时,研究还发现社区缺乏对NTD的健康教育,社区没有充分认识到疾病预防的责任,社区志愿者力量尚未得到可持续发展.结论:APOC项目目标部分得到实现,与其他非洲国家相比,尼日利亚在项目实施上遇到一些挑战和困难.该项目对于中国也具有借鉴意义.%Objective: To investigate the progress and challenges of the implementation of the global programme in Taraba State, Nigeria. Methods; The African Programme for Onchocerciasis Control ( APOC) as the first neglected tropical diseases ( 1NTD ) control initiative in Africa had been introduced to Nigeria since 1997. Community-directed distributors of community-directed treatment with ivermectin had been adopted as its main strategy. As a qualitative study, in-depth interview and focus group discussion were used as data collection methods. The thematic framework method was used as a data analysis method. Results: The community reported that they had benefited from the programme. The study findings showed that the health education on NTDs remained very poor, and the community had not fully realized its responsibility for the drug distribution and NTDs control, and the community drug distributor (CDDs) had not been developed as a substantial team working for other projects. Conclusion; The goals of community-directed treatment with ivermectin (CDTI) only have been achieved partly. China should learn from the experience.
Larivière, M; Beauvais, B; Derouin, F; Basset, D; Basset, A; Sarfati, C
Ivermectin is a synthetic derivative of a macrocyclic lactone produced by an actinomycete Streptomyces avermitilis. It has a broad spectrum antiparasitic activity against nematodes and certain acarians in animals. The microfilaricide action of this product against horse and cattle onchocercosis led to the study of its effects in human onchocercosis against O. volvulus. Several trials performed mainly in endemic zones of Africa showed that this drug was more effective than the reference microfilaricide, diethylcarbamazine. A single oral dose of 200 micrograms/kg of Ivermectin reduces the dermal microfilaria population to nearly zero within a few days and the effect is maintained for at least 6 months. Secondary ocular or systemic effects are rare, negligible and transitory. The prolonged elimination of dermal microfilariasis caused by sequestration followed by degeneration of the microfilaria in the uterus of females raises the hope that Ivermectin used in a single annual or bi-annual dose will contribute to the interruption of the transmission of this serious parasitic disease.
... With Particular Reference To Females And Children: A Review. ... to urban areas, reducing the productivity of the community and disrupting family life. ... This affects their age of marriage and the kind of partners they marry, limiting them to ...
Tielsch, James M; Beeche, Arlyne
.... With over 250 million doses of ivermectin distributed over the past 15 years, the MDP is well on its way to both solidifying the progress made by the OCP and extending program reach well beyond...
Full Text Available The evolution and persistence of ocular pathology was assessed in a cohort of Onchocerca volvulus infected patients treated annually with ivermectin for 23 years. Patients were resident in rural Central and Kara Region of Togo and ocular examinations included testing of visual acuity, slit lamp examination of the anterior eye segment and the eye fundus by ophthalmoscopy. Before ivermectin treatment, vivid O.volvulus microfilariae (MF were observed in the right and left anterior eye chamber in 52% and 42% of patients (n = 82, and dead MF were seen in the right and left cornea in 24% and 15% of cases, respectively. At 23 years post initial treatment (PIT, none of the patients (n = 82 presented with MF in the anterior chamber and cornea. A complete resolution of punctate keratitis (PK lesions without observable corneal scars was present at 23 years PIT (p<0.0001, and sclerosing keratitits (SK lessened by half, but mainly in patients with lesions at early stage of evolution. Early-stage iridocyclitis diminished from 42%(rE and 40%(lE to 13% (rE+lE(p<0.0001, but advanced iridocyclitis augmented (p<0.001 at 23 years PIT compared to before ivermectin. Advanced-stage papillitis and chorioretinitis did not regress, while early-stage papillitis present in 28%(rE and 27%(lE of patients at before ivermectin regressed to 17%(rE and 18%(lE, and early-stage chorioretinitis present in 51%(rE+lE of cases at before ivermectin was observed in 12%(rE and 13%(lE at 23 years PIT (p<0.0001. Thus, regular annual ivermectin treatment eliminated and prevented the migration of O. volvulus microfilariae into the anterior eye chamber and cornea; keratitis punctata lesions resolved completely and early-stage sclerosing keratitits and iridocyclitis regressed, whilst advanced lesions of the anterior and posterior eye segment remained progressive. In conclusion, annual ivermectin treatments may prevent the emergence of ocular pathology in those populations still exposed to O.volvulus infection.www.pactr.org PACTR201303000464219.
Shu, E N; Okonkwo, P O; Ogbodo, S O
The introduction of ivermectin therapy has proved to be the most important advance in the management and control of onchocerciaisis. By using the standard dosing schedule (150 micrograms/kg) in a mass chemotherapy campaign in Awhum, Nigeria, 128 (14.6%) of 875 eligible subjects used in this study were underdosed while 696 (79.6%) and 51 (5.8%) were overdosed and correctly dosed, respectively. Since underdosing is more serious than overdosing, an improved dosing schedule (300 micrograms/kg) is hereby suggested, bearing in mind that ivermectin is safe at doses well in excess of the standard dose. 824 (94.2%) And 51 (5.8%) of these eligible subjects would be overdosed and correctly dosed respectively, if this improved dosing schedule ( 60 kg, 24 mg (4 tablets)) were to be employed. This dosing schedule is worth adopting and an investigation of the effects of these high single doses of ivermectin on adult Onchocerca volvolus worms is advocated. Furthermore 'non-responders' may be investigated for doses administered.
Bulman, Christina A; Bidlow, Chelsea M; Lustigman, Sara; Cho-Ngwa, Fidelis; Williams, David; Rascón, Jr, Alberto A; Tricoche, Nancy; Samje, Moses; Bell, Aaron; Suzuki, Brian; Lim, K C; Supakorndej, Nonglak; Supakorndej, Prasit; Wolfe, Alan R; Knudsen, Giselle M; Chen, Steven; Wilson, Chris; Ang, Kean-Hooi; Arkin, Michelle; Gut, Jiri; Franklin, Chris; Marcellino, Chris; McKerrow, James H; Debnath, Anjan; Sakanari, Judy A
.... The drugs ivermectin, diethylcarbamazine (DEC), and albendazole are used in control programs for these diseases, but are mainly effective against the microfilarial stage and have minimal or no effect on adult worms...
Taylor, Mark J; Hoerauf, Achim; Townson, Simon; Slatko, Barton E; Ward, Stephen A
Anti-Wolbachia therapy delivers safe macrofilaricidal activity with superior therapeutic outcomes compared to all standard anti-filarial treatments, with the added benefit of substantial improvements in clinical pathology. These outcomes can be achieved, in principle, with existing registered drugs, e.g. doxycycline, that are affordable, available to endemic communities and have well known, albeit population-limiting, safety profiles. The key barriers to using doxycycline as an mass drug administration (MDA) strategy for widespread community-based control are the logistics of a relatively lengthy course of treatment (4-6 weeks) and contraindications in children under eight years and pregnancy. Therefore, the primary goal of the anti-Wolbachia (A·WOL) consortium is to find drugs and regimens that reduce the period of treatment from weeks to days (7 days or less), and to find drugs which would be safe in excluded target populations (pregnancy and children). A secondary goal is to refine regimens of existing antibiotics suitable for a more restricted use, prior to the availability of a regimen that is compatible with MDA usage. For example, for use in the event of the emergence of drug-resistance, in individuals with high loiasis co-infection and at risk of severe adverse events (SAE) to ivermectin, or in post-MDA 'endgame scenarios', where test and treat strategies become more cost effective and deliverable.
Awadzi, K; Adjepon‐Yamoah, KK; Edwards, G; Orme, ML; Breckenridge, AM; Gilles, HM
...) citrate twice daily for 10 days. In 11 patients the urine was made alkaline with sodium bicarbonate, 2 g, administered 6 hourly for three doses daily beginning 1 day before DEC was started and continued throughout the DEC therapy...
Awadzi, K; Attah, S K; Addy, E T; Opoku, N O; Quartey, B T
Ivermectin, at the standard dose of 150 micrograms/kg bodyweight, does not kill the adult worms of Onchocerca volvulus and does not disrupt embryogenesis or spermatogenesis. Repeated standard doses, if maintained, arrest microfilarial production but result in only a mild-to-modest macrofilaricidal effect. We investigated whether high doses would effectively kill the adult worms, and whether cessation of microfilarial production could be reproduced by an equivalent, single, high dose. One hundred men participated in a double-blind placebo-controlled trial and received increasing doses of ivermectin from 150 micrograms/kg to 1600 micrograms/kg bodyweight. Nodules were excised at day 180 and examined by histopathology. Total doses of ivermectin up to 1600 micrograms/kg were not significantly more effective than 150 micrograms/kg. Moreover, they did not reproduce the marked inhibitory effects of the repeat standard-dose regimens on embryogenesis, nor the modest effect on adult worm viability, at comparable total doses. These effects may be functions of multiplicities of dosages rather than of the total dose. Our findings also suggest that repeated high-dose regimens are unlikely to be more effective than a similar number of 150 micrograms/kg doses. This deficiency of ivermectin requires that the search for macrofilaricides remains a top priority.
Greene, B M; Taylor, H R; Brown, E J; Humphrey, R L; Lawley, T J
Diethylcarbamazine (DEC) therapy for Onchocerca volvulus infection results in frequent ocular and systemic complications, but the pathogenesis of these complications is unclear. Twenty men with O. volvulus infection were treated over a period of six months with DEC given daily for one week and weekly thereafter. Major systemic and ocular complications included proteinuria, severe pruritus, visual field constriction, optic nerve pallor, chorioretinitis, anterior uveitis, and punctate keratitis. Levels of circulating immune complexes (CICs) were increased (greater than 11% [125I]C1q binding) in 14 of the 20 men prior to treatment. Persons with pretreatment C1q binding activity of greater than 30% were at increased risk to develop constriction of visual fields (P less than 0.05) and proteinuria (P less than 0.015). Linear regression analysis revealed a striking correlation between pretreatment levels of CICs and the total number of both systemic and ocular complications (P less than 0.001) and ocular complications alone (P less than 0.005). These results suggest that CICs may be important in the pathogenesis of the delayed systemic and ocular complications following DEC therapy for O. volvulus infection.
Collins, R C; Brandling-Bennett, A D; Holliman, R B; Campbell, C C; Darsie, R F
Tissue culture fluid NCTC 135 (Hank's base) was compared to water and to saline as incubation media for the detection of microfilariae of Onchocerca volvulus in skin snips. NCTC 135 allowed detection of significantly more positive persons than did water (P less than 0.001) or saline (P less than 0.05) when two snips per person were incubated for periods of 0.5 or 24 hours. In addition, snips containing microfilariae were incubated in NCTC 135 or in saline and the number of emerged microfilariae was determined at various intervals of time up to 24 hours. After incubation, snips were either fixed in 10% formalin, serially sectioned, and the microfilariae counted, or they were digested in collagenase solution to free unemerged microfilaire. Of the total number of microfilariae present in the snips, 43.9% +/- 18.5, 80.2% +/- 22.2, 83.0% +/- 19.5, and 85.3% +/- 18.0 had emerged by 0.5, 4, 8, and 24 hours of incubation, respectively. Of the microfilariae that remained in the skin after incubation, most were located deep in the dermis.
Francis, H; Awadzi, K; Ottesen, E A
To determine definitively whether or not the severity of the Mazzotti reaction was correlated with infection intensity, as determined by skin snip quantification, 21 infected Ghanian patients were evaluated during 7 days of treatment with 200 mg/day of diethylcarbamazine. Serial blood, urine and skin biopsy samples were collected during the progression of the Mazzotti reaction. Hypotension, fever, adenitis and pruritus were all correlated with infection intensity in these patients while arthralgia and tachycardia were not. Peripheral blood eosinopenia and neutrophilia also correlated with intensity of infection and appeared to reflect the accumulation of degranulating eosinophils around "mobilized" microfilariae that migrated from the dermis to the epidermis after diethylcarbamazine (DEC). Other mobilized microfilariae apparently were cleared by the liver and resulted in abnormal liver enzyme levels in the serum which, again, were directly correlated with the patients' microfilarial density. Though the severity of the Mazzotti reaction clearly correlated with intensity of infection, the different times of onset of symptoms, and cellular and serum chemistry changes indicate that there are probably multiple infection intensity-dependent mechanisms responsible for mediating this complex reaction.
Kelly-Hope, Louise A; Unnasch, Thomas R; Stanton, Michelle C; Molyneux, David H
...) is targeted for elimination in Africa. This is a significant change in strategy from the 'control' of meso- and hyper-endemic areas through mass drug administration (MDA) with Mectizan® (ivermectin...
Albiez, E J
60 completely nodulectomized volunteers from the Liberian rain-forest were given an initial treatment with diethylcarbamazine citrate (DEC-C) for one week with gradually increasing doses up to a total of 1.1 g per patient. A long-term treatment followed with 50 mg DEC-C per week for 12 months. Immediately after the initial treatment the mean microfilarial density decreased to 4% to 6% of the pre-treatment level. After one year the microfilarial density had again increased to 12% to 29% of the pre-treatment level. Although the intake of the weekly 50 mg DEC-C was in no case regular, the microfilarial densities could be kept at a low level throughout the trial. However, even with the combined treatment--preceding nodulectomy and long-term trial with DEC-C--it was not possible to get the patients free from microfilariae.
Mahé, E; Torchet, M F; Chrétiennot, C; Buffet, P; Bodemer, C
'River blindness' is the main problem of onchocerciasis. Despite a high prevalence of onchocerciasis in endemic countries, cases of imported cutaneous or ocular onchocerciasis in France are rare. We report the case of a chronic papular onchodermatitis with voluminous lymphadenopathy in a Cameroonian child, resolving with a treatment of ivermectin. The main symptom of cutaneous onchocerciasis is pruritus, which symptom may alert physicians when dealing with patients who come from endemic countries for onchocerciasis. Cutaneous aspects may vary depending on length of exposure to antigens and immune responses by the host against microfilariae. Nowadays, onchocerciasis is treated with a single dose of ivermectin, which is sufficient for eye and cutaneous symptoms. However, this therapy is efficient only against microfilariae, and treatments have to be repeated many times to avoid relapses linked to persistence of adult worms.
Thomas S. Churcher; Sébastien D. S. Pion; Mike Y. Osei-Atweneboana; Roger K. Prichard; Kwablah Awadzie; Michel Boussinesq; Richard C. Collins; James A. Whitwort; Maria-Gloria Basanez; David Cox
.... The variability in the rate at which Onchocerca volvulus microfilariae repopulate host's skin following ivermectin treatment is quantified using an individual-based onchocerciasis mathematical model...
.... His book covers mosquito-, tick-, and flea-borne diseases, and a variety of other miscellaneous vector-borne diseases, including Chagas' disease, African sleeping sickness, onchocerciasis, scrub...
Rodríguez-Pérez, M A; Rivas-Alcalá, A R
The treatment and control of onchocerciasis in Mexico has been supported only on the administration of diethylcarbamazine and the removal of adult worms, which are in the onchocercomata. These actions seems to have diminished the prevalence and incidence of blindness in those individuals who are affected by this parasitosis. However, there has not been an important impact on onchocerciasis transmission. The objective of this paper is to critically analyze and discuss subjects related to diagnosis, treatment and control of onchocerciasis transmission in Mexico. Chemical vector control has been successfully achieved in other world regions; however, in Mexico, it has not been fully accepted as part of the integral onchocerciasis control due to several causes. Moreover, there has been few scientific research activities toward the search of new options for vector control. Recently, results of research on ivermectin (a microfilaricide agent) have indicated that this drug is effective and safe for the treatment of onchocerciasis. Additionally, it has been reported that ivermectin has an effect on the onchocerciasis transmission. However, there are several unanswered questions about the efficacy of ivermectin in stopping onchocerciasis transmission. In this report, the main efforts carried out in Mexico against onchocerciasis are analysed and problems related with diagnosis, treatment and control are also discussed. Some parameters for the correct evaluation of onchocerciasis control, with entomological emphasis, are proposed.
Gonzalez, Rodrigo J; Cruz-Ortiz, Nancy; Rizzo, Nidia; Richards, Jane; Zea-Flores, Guillermo; Domínguez, Alfredo; Sauerbrey, Mauricio; Catú, Eduardo; Oliva, Orlando; Richards, Frank O; Lindblade, Kim A
.... We evaluated whether transmission of onchocerciasis has been interrupted in the endemic focus of Escuintla-Guatemala in Guatemala, based on World Health Organization criteria for the certification...
Daehnel, K; Gillette-Ferguson, I; Hise, A G; Diaconu, E; Harling, M J; Heinzel, F P; Pearlman, E
Toll-like receptors (TLRs) regulate dendritic cell function and activate signals that mediate the nature of the adaptive immune response. The current study examined the role of TLRs in dendritic cell activation and in regulating T cell and antibody responses to antigens from the filarial parasites Onchocerca volvulus and Brugia malayi, which cause river blindness and lymphatic filariasis, respectively. Bone-marrow-derived CD11c(+) cells from C57BL/6 and TLR4(-/-) mice produced high levels of IL-6 and RANTES, and showed elevated surface CD40 expression, whereas CD11c(+) cells from myeloid differentiation factor 88(-/-) (MyD88(-/-)), TLR2(-/-) and TLR2/4(-/-) mice were not activated. Similarly, IFN-gamma production by splenocytes from immunized TLR2(-/-) mice was significantly impaired compared with splenocytes from C57BL/6 and TLR4(-/-) mice. In contrast, there was no difference among these strains in Th2-associated responses including IL-5 production by splenocytes from immunized animals, serum IgE and IgG(1), or eosinophil infiltration into the corneal stroma. Neutrophil recruitment to the cornea and CXC chemokine production was inhibited in immunized TLR2(-/-) mice compared with C57BL/6 and TLR4(-/-) mice. Taken together, these findings demonstrate an essential role for TLR2 in filaria-induced dendritic cell activation, IFN-gamma production and neutrophil migration to the cornea, but does not affect filaria-induced Th2-associated responses.
such as malaria, schistosomiasis, filariasis, onchocerciasis and tick-borne relapsing fever. ... explains the role of multi-sectoral and integrated approaches that are cost-effective in the control ..... Programme Action the World Bank; Washington.
Full Text Available (drug) Cupp EW, Sauerbrey M, Richards F Elimination of human onchocerciasis: history of progress and current feasibility using iverme...ctin (Mectizan((R))) monotherapy. Acta Trop 120 Suppl 1:
however, should be revisited since functional blindness is attained .... term sustainability and effectiveness of ivermectin in preventing visual ... ophthalmic surgeons and their teams, expectations of outcome ..... Cross С Onchocerciasis. Lecture ...
González-Muñoz, M; Gárate, T; Puente, S; Subirats, M; Moneo, I
The host immune response in onchocerciasis is believed to contribute to the clinical manifestations of infection. Mazzotti and chronic inflammatory reactions might be mediated by mechanisms involving specific IgE and reactivity of mast cells and basophils to the parasite antigens. In this report, we show that Onchocerca volvulus antigens are capable of inducing histamine release. Three types of extracts were prepared from the parasite: soluble total, surface, and cuticular collagen. Soluble extracts released histamine in all individuals with onchocerciasis at significantly higher levels (P < 0.05) than those found in endemic controls, but similar levels to those found in patients with mansonellosis. However, cuticular collagen induced significantly (P < 0.01) higher histamine release in patients with onchocerciasis than in those with mansonellosis. No reactivity against human type IV collagen was observed. Implications derived from the presence of sensitized basophils in the pathogenesis of onchocerciasis are discussed.
Lustigman, Sara; Makepeace, Benjamin L; Klei, Thomas R; Babayan, Simon A; Hotez, Peter; Abraham, David; Bottazzi, Maria Elena
Human onchocerciasis - commonly known as river blindness - is one of the most devastating yet neglected tropical diseases, leaving many millions in sub-Saharan Africa blind and/or with chronic disabilities. Attempts to eliminate onchocerciasis, primarily through the mass drug administration of ivermectin, remains challenging and has been heightened by the recent news that drug-resistant parasites are developing in some populations after years of drug treatment. Needed, and needed now, in the fight to eliminate onchocerciasis are new tools, such as preventive and therapeutic vaccines. This review summarizes the progress made to advance the onchocerciasis vaccine from the research laboratory into the clinic. Copyright © 2017 Elsevier Ltd. All rights reserved.
transmission dynamics and control of Onchocerciasis was developed ... varying population size (birth rate not equal to death removal rate), and standard ... ordinary differential equations. ..... Diseases: Model building, analysis and. Integration.
Kamgno, Joseph; Nguipdop-Djomo, Patrick; Gounoue, Raceline; Téjiokem, Mathurin; Kuesel, Annette C
.... Loiasis can be co-endemic with onchocerciasis and/or lymphatic filariasis. Ivermectin, the drug used in the control of these diseases, can induce serious adverse reactions in patients with high L loa microfilaraemia (LLM...
Turner, Joseph D; Tendongfor, Nicholas; Esum, Mathias; Johnston, Kelly L; Langley, R Stuart; Ford, Louise; Faragher, Brian; Specht, Sabine; Mand, Sabine; Hoerauf, Achim; Enyong, Peter; Wanji, Samuel; Taylor, Mark J
The risk of severe adverse events following treatment of onchocerciasis with ivermectin in areas co-endemic with loiasis currently compromises the development of control programmes and the treatment...
Cost-effectiveness analysis of Mectizan treatment Programmes for Onchocerciasis Control: Operational Experiences in two districts of Southwestern Nigeria. ... Vol 8, No 1 (2009) >. Log in or Register to get access to full text downloads.
Cousens, S N; Cassels-Brown, A; Murdoch, I; Babalola, O E; Jatau, D; Alexander, N D; Evans, J E; Danboyi, P; Abiose, A; Jones, B R
Reported are the results of a randomized, double-masked, placebo-controlled trial of annual ivermectin dosing in 34 rural communities, Kaduna State, northern Nigeria, where guinea savanna onchocerciasis is mesoendemic...
Awadzi, K; Opoku, Nicholas O; Attah, Simon K; Lazdins-Helds, Janis K; Kuesel, Annette C
.... The Onchocerciasis Control Programme (OCP) had established procedures to detect O. volvulus infections via the localized skin reaction induced by killing of microfilariae upon skin exposure to diethylcarbamazine via a patch (OCP-patch...
Jul 26, 2017 ... eye with or without pain, history suggestive of measles, trachoma, onchocerciasis and .... Table 2: Distribution of the causes of corneal blindness. Causes of cornea blindness ... Periodic health education on the need for timely ...
Ejere, HO; Schwartz, E; Wormald, R; Evans, JR
BACKGROUND: It is believed that ivermectin (a microfilaricide) could prevent blindness due to onchocerciasis. However, when given to everyone in communities where onchocerciasis is common, the effects of ivermectin on lesions affecting the eye are uncertain and data on whether the drug prevents visual loss are unclear. OBJECTIVES: The aim of this review was to assess the effectiveness of ivermectin in preventing visual impairment and visual field loss in onchocercal eye disease. The secondary...
Onchocerciasis continues to be a major cause of blindness, particularly in those sub-Saharan African countries which are outside the area of West Africa monitored by the Onchocerciasis Control Programme (OCP). Onchocercal ocular disease and blindness develop as a result of long exposure to onchocercal infection. Until 1987, suramin and diethylcarbamazine were the only drugs available for the treatment of onchocerciasis and they could not be used for community therapy because of their toxicity and the dosage schedules required. The registration of Mectizan (ivermectin, MSD) for treatment of human onchocerciasis in 1987, and the donation of this drug by Merck & Co. for as long as it is needed, provided a new opportunity for the safe treatment and control of the disease. The data available on the impact of repeated doses of Mectizan on ocular onchocercal disease indicate a significant reduction of ocular microfilarial loads and regression of early lesions of the anterior segment, including iridocyclitis and sclerosing keratitis. Such improvements are seen more rapidly when Mectizan is used than when onchocerciasis is limited by vector control alone. Mectizan treatment also has a beneficial effect on onchocercal optic-nerve disease and visual-field loss. Long-term maintenance of Mectizan therapy should lead to a reduction in the prevalence of blindness in endemic communities.
Kyelem, D; Sanou, S; Boatin, B; Medlock, J; Coulibaly, S; Molyneux, D H
Parasitological and clinical surveys were used to determine the long-term impact of ivermectin on the prevalence of Wuchereria bancrofti and Mansonella perstans filarial infections, when the drug was given under community-directed-treatment strategies for onchocerciasis control. The study was undertaken in 11 communities in south-western Burkina Faso. Six of the villages investigated had been treated with ivermectin at least once a year for five of 6 years, with a mean coverage of approximately 65% in each round. The other five, adjacent villages, which were matched with the ivermectin-treated communities by size, ethnicity and social and economic activities, had never been treated because they were not endemic for onchocerciasis. Each subject was checked by the microscopical examination of a smear of 'night' blood, by measurement of the level of circulating antigens from adult W. bancrofti, and by clinical examination for hydrocele (if male) and lymphoedema. The prevalences of lymphoedema and hydrocele in the treated villages were similar to those in the untreated. The prevalences and intensities of W. bancrofti and M. perstans microfilaraemia were, however, significantly lower in the ivermectin-treated communities. The implications of this study are discussed in relation to the old Onchocerciasis Control Programme (OCP) and to the ongoing African Programme for Onchocerciasis (APOC), where extensive and sustained ivermectin distribution is planned through community-based treatment programmes. As with onchocerciasis in Africa, the success of annual treatments to control lymphatic filariasis will depend not only on the number of regular rounds of treatment given but on adequate coverages being achieved in each round. Wherever ivermectin is being distributed alone, for onchocerciasis control, its impact on other filarial infections, notably W. bancrofti, should be evaluated routinely. Any opportunity to add donated albendazole to such distributions should be taken
Pedersen, B K; Bygbjerg, Ib Christian; Svenson, M
Two patients, one with Bancroftian filariasis and the other with onchocerciasis, and two healthy controls were treated with diethylcarbamazine (DEC). The natural killer (NK) cell activity of the two patients increased during DEC treatment to 2.5 and 2.8 times, respectively, while...... that of the controls remained unchanged. We conclude that the augmentation of baseline NK cell activity, as well as interferon- and interleukin-2-enhanced NK cell activity seen in the patients, is not a direct effect of DEC, but is related to the reaction to DEC in lymphatic filariasis and onchocerciasis....
Pedersen, B K; Bygbjerg, I C; Svenson, M
Two patients, one with Bancroftian filariasis and the other with onchocerciasis, and two healthy controls were treated with diethylcarbamazine (DEC). The natural killer (NK) cell activity of the two patients increased during DEC treatment to 2.5 and 2.8 times, respectively, while that of the controls remained unchanged. We conclude that the augmentation of baseline NK cell activity, as well as interferon- and interleukin-2-enhanced NK cell activity seen in the patients, is not a direct effect of DEC, but is related to the reaction to DEC in lymphatic filariasis and onchocerciasis.
Kevin L Winthrop
Full Text Available For decades, onchocerciasis (or river blindness was one of the most common infectious causes of blindness in the world. Primarily an infection of Africa, with limited distribution in the new world, disease due to the nematode Onchocerca volvulus is rapidly diminishing as a result of large public health campaigns targeting at risk populations in Africa and the Americas. Existing and newly-developed treatment strategies offer the chance to eliminate onchocercal ocular morbidity in some parts of the world. This article reviews these treatment strategies, current clinical and epidemiologic aspects of onchocerciasis, and the next steps toward elimination.
Full Text Available An increased prevalence of epilepsy has been reported in many onchocerciasis endemic areas.To determine the prevalence and distribution of epilepsy in an onchocerciasis endemic region in the Democratic Republic of the Congo (DRC.An epilepsy prevalence study was carried out in 2014, in two localities of the Bas-Uélé district, an onchocerciasis endemic region in the Orientale Province of the DRC. Risk factors for epilepsy were identified using a random effects logistic regression model and the distribution of epilepsy cases was investigated using the Moran's I statistic of spatial auto-correlation.Among the 12,776 individuals of Dingila, 373 (2.9% individuals with epilepsy were identified. In a house-to-house survey in Titule, 68 (2.3% of the 2,908 people who participated in the survey were found to present episodes of epilepsy. Epilepsy showed a marked spatial pattern with clustering of cases occurring within and between adjacent households. Individual risk of epilepsy was found to be associated with living close to the nearest fast flowing river where blackflies (Diptera: Simuliidae-the vector of Onchocerca volvulus-oviposit and breed.The prevalence of epilepsy in villages in the Bas-Uélé district in the DRC was higher than in non-onchocerciasis endemic regions in Africa. Living close to a blackflies infested river was found to be a risk factor for epilepsy.
Y.E. Kim (Young Eun); J.H.F. Remme (Jan); P. Steinmann (Peter); W.A. Stolk (Wilma); J.-B. Roungou (Jean-Baptiste); F. Tediosi (Fabrizio)
textabstractRiver blindness (onchocerciasis) causes severe itching, skin lesions, and vision impairment including blindness. More than 99% of all current cases are found in sub-Saharan Africa. Fortunately, vector control and community-directed treatment with ivermectin have significantly reduced mor
Meredith Stefanie E O
Full Text Available Abstract The control of onchocerciasis is not only a major success story in global health, but also one of the best examples of the power of public-private partnership at the international level as well as at the national level. The onchocerciasis story is also a leading example of the contribution of a group of called Non-Governmental Development Organizations (NGDO to operational research which resulted in important changes in treatment strategies and policies. The four case studies presented here illustrate some key contributions the NGDOs made to the development of “community directed treatment with ivermectin” –CDTI, in Africa, which became the approved methodology within the African Programme for Onchocerciasis Control (APOC. The partnership between the international, multilateral, government institutions and the NGDO Coordination Group was the backbone of the APOC programme’s structure and facilitated progress and scale-up of treatment programmes. Contributions included piloting community–based methodology in Mali and Nigeria; research, collaboration and coordination on treatment strategies and policies, coalition building, capacity building of national health workforce and advocacy at the national and international level. While the Onchocerciasis Control Programme (OCP and APOC provided leadership, the NGDOs working with the national health authorities played a major role in advocacy evolving the community methodology which led to achieving and maintaining- treatments with ivermectin for at least 20 years and strengthening community health systems.
This report summarizes the available information on the immunology of filariasis, and discusses immunodiagnosis and the immunological factors influencing the host—parasite relationship in lymphatic filariasis and onchocerciasis. Several areas that require further research are identified, particularly concerning the development of new serological techniques, and the fractionation of specific antigens. The problems associated with vaccine development are considered and the importance of finding...
Studies conducted during the past 25 years to investigate the possible relationship between ... investigation of a possible relationship between onchocerciasis and epilepsy, we ... occurring in the brain, and which can be more ... and Bangoua in the West region of Cameroon. ... (Tume et al., 1997), using O. volvulus-specific.
Rodrigo J Gonzalez
Full Text Available BACKGROUND: Elimination of onchocerciasis (river blindness through mass administration of ivermectin in the six countries in Latin America where it is endemic is considered feasible due to the relatively small size and geographic isolation of endemic foci. We evaluated whether transmission of onchocerciasis has been interrupted in the endemic focus of Escuintla-Guatemala in Guatemala, based on World Health Organization criteria for the certification of elimination of onchocerciasis. METHODOLOGY/PRINCIPAL FINDINGS: We conducted evaluations of ocular morbidity and past exposure to Onchocerca volvulus in the human population, while potential vectors (Simulium ochraceum were captured and tested for O. volvulus DNA; all of the evaluations were carried out in potentially endemic communities (PEC; those with a history of actual or suspected transmission or those currently under semiannual mass treatment with ivermectin within the focus. The prevalence of microfilariae in the anterior segment of the eye in 329 individuals (> or =7 years old, resident in the PEC for at least 5 years was 0% (one-sided 95% confidence interval [CI] 0-0.9%. The prevalence of antibodies to a recombinant O. volvulus antigen (Ov-16 in 6,432 school children (aged 6 to 12 years old was 0% (one-sided 95% IC 0-0.05%. Out of a total of 14,099 S. ochraceum tested for O. volvulus DNA, none was positive (95% CI 0-0.01%. The seasonal transmission potential was, therefore, 0 infective stage larvae per person per season. CONCLUSIONS/SIGNIFICANCE: Based on these evaluations, transmission of onchocerciasis in the Escuintla-Guatemala focus has been successfully interrupted. Although this is the second onchocerciasis focus in Latin America to have demonstrated interruption of transmission, it is the first focus with a well-documented history of intense transmission to have eliminated O. volvulus.
Wagbatsoma, V A; Okojie, O H
Onchocerciasis (river blindness) is a serious public health problem with important socioeconomic consequences. The presence of onchocercal skin lesions is unsightly and has a psychosocial effect on the affected. This cross-sectional study was undertaken to assess the perception and social implication of onchocerciasis in the village of Apana in Nigeria. Apana is a rural community, hyper-endemic for onchocerciasis and currently receiving ivermectin treatment. The village is one of the ten communities of Uzairue district of Etsako West Local Government Area (LGA), Edo State, Nigeria. There are many water streams in the community which serve the domestic needs of the inhabitants but also provide the breeding sites for the vector flies of onchocerciasis. Multi-stage sampling methods were used to select the 385 respondents that participated after informed consent was obtained. A structured researcher-administered questionnaire was the tool for data collection. Of the 385 respondents that participated in the survey, 240 (62.3%) were male while 145 (37.7%) were female. The awareness of the disease among the respondents was fair. They were aware of the nuisance value of blackflies ('Uja-ini') and associated the bite with itching. The signs and symptoms of onchocerciasis were recognised as specific diseases with specific local names. They called itching and rashes 'Erhue', nodules and leopard skin 'Evbiomu-Ogui', worm in the eye 'Okogho-Ikpalo' and blindness 'Orunalo'. The attitude of the non-affected towards the affected was partially discriminatory and suspicious. The affected were socially withdrawn, probably due to the frustration of their health condition. There is a need to improve people's attitude towards the disease and improve disease awareness through appropriate health education, which will encourage the acceptance of ivermectin as adequate treatment and compliance to the treatment regimen to reduce morbidity and promote self-esteem.
The UN Development Program/World Bank/World Health Organization's Special Program for Research and Training in Tropical Diseases hosted a meeting in January 1998 to discuss new ways of generating sustained commitment to combat disabling tropical diseases, such as filariasis and onchocerciasis. The participants agreed that advocacy should be targeted to a wider audience than the health sector, including international donors, industry, national governments, and endemic communities themselves. Advocacy efforts will be supported by development of a standard protocol that will 1) identify and present the type of evidence that generates sustainable commitment, 2) develop and use appropriate messages for each audience, 3) evaluate new advocacy approaches for their impact on behavioral change and disease control, and 4) evaluate advocacy campaigns. Advocacy about lymphatic filariasis will target all levels, while advocacy about onchocerciasis will target national and local levels.
Rodríguez-Pérez, Mario A; Lutzow-Steiner, Miguel A; Segura-Cabrera, Aldo; Lizarazo-Ortega, Cristian; Domínguez-Vázquez, Alfredo; Sauerbrey, Mauricio; Richards, Frank; Unnasch, Thomas R; Hassan, Hassan K; Hernández-Hernández, Raymundo
The impact of quarterly Mectizan (ivermectin) treatments on transmission, microfiladermia, and ocular lesions was evaluated in two formerly hyperendemic communities (Las Golondrinas and Las Nubes II) located in the main endemic focus for onchocerciasis in Southern Chiapas, Mexico. The data suggest that Onchocerca volvulus transmission has been suppressed after elimination of microfiladermia in these two communities. Increasing the frequency of Mectizan treatment to four times per year appears to have resulted in the rapid suppression of transmission in communities with residual transmission.
Prevention of blindness is the most important aim of ophthalmology. Prevention of blindness is related to many factors. It is related to many factors, such as science and technology, economy and social behavior. There are worldwide activities by WHO, NGOs and other functions to promote the prevention of blindness in the world. More than 90% of blind population lives in developing world. Cataract is the top causes of blindness which is curable. Onchocerciasis is an endemic disease in west Africa and cent...
Kobylinski, Kevin C; Sylla, Massamba; Chapman, Phillip L.; Sarr, Moussa D.; Foy, Brian D
Ivermectin mass drug administration (MDA) to humans is used to control onchocerciasis and lymphatic filariasis. Recent field studies have shown an added killing effect of ivermectin MDA against malaria vectors. We report that ivermectin MDA reduced the proportion of Plasmodium falciparum infectious Anopheles gambiae sensu stricto (s.s.) in treated villages in southeastern Senegal. Ivermectin MDA is a different delivery method and has a different mode of action from current malaria control age...
Benjamin G Jacob
Full Text Available BACKGROUND: Recently, most onchocerciasis control programs have begun to focus on elimination. Developing an effective elimination strategy relies upon accurately mapping the extent of endemic foci. In areas of Africa that suffer from a lack of infrastructure and/or political instability, developing such accurate maps has been difficult. Onchocerciasis foci are localized near breeding sites for the black fly vectors of the infection. The goal of this study was to conduct ground validation studies to evaluate the sensitivity and specificity of a remote sensing model developed to predict S. damnosum s.l. breeding sites. METHODOLOGY/PRINCIPAL FINDINGS: Remote sensing images from Togo were analyzed to identify areas containing signature characteristics of S. damnosum s.l. breeding habitat. All 30 sites with the spectral signature were found to contain S. damnosum larvae, while 0/52 other sites judged as likely to contain larvae were found to contain larvae. The model was then used to predict breeding sites in Northern Uganda. This area is hyper-endemic for onchocerciasis, but political instability had precluded mass distribution of ivermectin until 2009. Ground validation revealed that 23/25 sites with the signature contained S. damnosum larvae, while 8/10 sites examined lacking the signature were larvae free. Sites predicted to have larvae contained significantly more larvae than those that lacked the signature. CONCLUSIONS/SIGNIFICANCE: This study suggests that a signature extracted from remote sensing images may be used to predict the location of S. damnosum s.l. breeding sites with a high degree of accuracy. This method should be of assistance in predicting communities at risk for onchocerciasis in areas of Africa where ground-based epidemiological surveys are difficult to implement.
Jacob, Benjamin G; Novak, Robert J; Toe, Laurent D; Sanfo, Moussa; Griffith, Daniel A; Lakwo, Thomson L; Habomugisha, Peace; Katabarwa, Moses N; Unnasch, Thomas R
Recently, most onchocerciasis control programs have begun to focus on elimination. Developing an effective elimination strategy relies upon accurately mapping the extent of endemic foci. In areas of Africa that suffer from a lack of infrastructure and/or political instability, developing such accurate maps has been difficult. Onchocerciasis foci are localized near breeding sites for the black fly vectors of the infection. The goal of this study was to conduct ground validation studies to evaluate the sensitivity and specificity of a remote sensing model developed to predict S. damnosum s.l. breeding sites. Remote sensing images from Togo were analyzed to identify areas containing signature characteristics of S. damnosum s.l. breeding habitat. All 30 sites with the spectral signature were found to contain S. damnosum larvae, while 0/52 other sites judged as likely to contain larvae were found to contain larvae. The model was then used to predict breeding sites in Northern Uganda. This area is hyper-endemic for onchocerciasis, but political instability had precluded mass distribution of ivermectin until 2009. Ground validation revealed that 23/25 sites with the signature contained S. damnosum larvae, while 8/10 sites examined lacking the signature were larvae free. Sites predicted to have larvae contained significantly more larvae than those that lacked the signature. This study suggests that a signature extracted from remote sensing images may be used to predict the location of S. damnosum s.l. breeding sites with a high degree of accuracy. This method should be of assistance in predicting communities at risk for onchocerciasis in areas of Africa where ground-based epidemiological surveys are difficult to implement.
Molyneux, David H
Gold standard diagnosis using blood films or skin snips has dimished relevance as mass drug distribution programmes for control of filaria infections expand. The view of 'diagnosis' and its relevance at the individual level has changed, as it has been recognised that the spectrum of programmatic processes (mapping, mass drug interventions, monitoring and evaluation, and surveillance) require different approaches as different questions are asked at each stage. The feasibility and relevance of skin biopsy or blood film examination is challenged when mass drug distribution seeks to treat all eligibles in communities. The need to expand programmes rapidly by identifying the highest risk communities has seen the development of rapid assessment methods, such as rapid epidemiological mapping of onchocerciasis (REMO) and rapid epidemiological assessment (REA) for onchocerciasis, immunochromatographic test (ICT)-based mapping for lymphatic filariasis (LF), and Rapid Assessment Procedure for Loiasis (RAPLOA) for Loa, to reduce the risk of serious adverse events and to guide projects in high-risk communities. As programmes reduce the prevalence through mass drug distribution, more sensitive techniques are required to define endpoints, for LF in particular where the programmatic goal is elimination; for onchocerciasis, sensitive surveillance tools are required particularly in those areas where such risks of recrudescence are high. Whilst much progress has been made in the development and deployment of rapid methods, there are still specific needs for antigen detection in onchocerciasis, whilst standardisation of a panel of tools for LF will allow the definition of endpoint parameters so that countries can decide when mass drug administration (MDA) can be stopped and have a sensitive post-MDA surveillance system.
Babalola, O E; Maegga, B; Katenga, S; Ogbuagu, F K; Umeh, R E; Seketeli, E; Braide, E
The goal of the African Programme for Onchocerciasis Control (APOC) is to eliminate Onchocerciasis as a disease of public Health significance and an important constraint to socio-economic development in the 19 none OCP (Onchocerciasis Control Project) countries covered through Community-Directed Treatment with Ivermectin, CDTI. In 1998, impact assessment studies were carried out in Morogoro, Tanzania during which baseline ophthalmological parameters were established. The hypothesis being tested is that CDTI will prevent or delay progression of onchocercal eye lesions and blindness. A total of 425 subjects aged 10 years or more from 14 villages within Bwakira district ofMorogoro region in Tanzania were examined for Snellen visual acuity, ocular microfilaria, lens opacities, uveitis and posterior segment disease especially chorioretinitis and optic nerve disease. Motion Sensitivity Screening Test (MSST) was carried out as well. Microfilaria was present in the anterior chamber of nearly half (49.2%) of all subjects examined. Prevalence of blindness was extremely high at 15.2%. Onchocercal lesions were responsible for blindness in 41.5% of these, followed by cataracts (27.7%), glaucoma (10.8%) and trachoma (6.2%). The main pathway to onchocercal blindness in this population was anterior uveitis with or without secondary cataracts. There is an urgent need to get CDTI underway and institute other horizontal primary eye care measures, especially cataract backlog reduction, in order to reduce the excessive burden of avoidable blindness in this community.
Full Text Available Wild female black flies attracted to a man or an idling automobile were collected at Oita, Japan where five cases of zoonotic onchocerciasis had occurred. Among the five Simulium species captured, 2% of Simulium bidentatum, the predominant species, were infected with filarial larvae. There were at least two types of infective larvae, types A and B, based on morphometric observation. Moreover, molecular analysis of the mitochondrial cytochrome c oxidase subunit 1 (CO1 gene revealed that types A and B were represented by a single unknown species of Onchocerca and two species, i.e., Onchocerca dewittei japonica from wild boar, the causative agent of zoonotic onchocerciasis in Japan, and an undescribed Onchocerca sp. from wild boar, respectively. Phylogenetic analysis based on the sequences of the mitochondrial 12S ribosomal RNA (12S rRNA gene also showed that type A is likely to be an unknown species of Onchocerca. Natural infection of black flies with infective larvae of O. dewittei japonica and O. sp. was demonstrated for the first time. The present study strongly suggests that S. bidentatum plays a role as a vector in the transmission of zoonotic onchocerciasis due to O. dewittei japonica in Japan.
Cruz-Ortiz, Nancy; Gonzalez, Rodrigo J.; Lindblade, Kim A.; Richards, Frank O.; Sauerbrey, Mauricio; Zea-Flores, Guillermo; Dominguez, Alfredo; Oliva, Orlando; Catú, Eduardo; Rizzo, Nidia
In Latin America, onchocerciasis is targeted for elimination by 2012 through twice-yearly mass treatment of the eligible population with ivermectin. In Guatemala, two of the four historical endemic foci have demonstrated elimination of transmission, following World Health Organization guidelines. Using established guidelines ophthalmological, serological, and entomological evaluations were conducted in 2007-8 to determine the transmission status of onchocerciasis in the Huehuetenango focus. The prevalence of Onchocerca volvulus microfilariae in the anterior segment of the eye in 365 residents was 0% (95% confidence interval [CI] 0–0.8%), the prevalence of infection of O. volvulus in Simulium ochraceum among 8252 flies collected between November 2007 and April 2008 was 0% (95% CI 0–0.02%), and the prevalence of antibodies to a recombinant O. volvulus antigen in 3118 school age children was 0% (95% CI 0–0.1%). These results showed transmission interruption; thus, in 2009 mass treatment was halted and posttreatment surveillance began. To verify for potential recrudescence an entomological evaluation (from December 2010 to April 2011) was conducted during the 2nd and 3rd year of posttreatment surveillance. A total of 4587 S. ochraceum were collected, and the prevalence of infection of O. volvulus was 0% (95% CI 0–0.04%). Transmission of onchocerciasis in the Huehuetenango focus has been eliminated. PMID:22970346
Hess, Jessica A; Zhan, Bin; Bonne-Année, Sandra; Deckman, Jessica M; Bottazzi, Maria Elena; Hotez, Peter J; Klei, Thomas R; Lustigman, Sara; Abraham, David
Human onchocerciasis is a neglected tropical disease caused by Onchocerca volvulus and an important cause of blindness and chronic disability in the developing world. Although mass drug administration of ivermectin has had a profound effect on control of the disease, additional tools are critically needed including the need for a vaccine against onchocerciasis. The objectives of the present study were to: (i) select antigens with known vaccine pedigrees as components of a vaccine; (ii) produce the selected vaccine antigens under controlled conditions, using two expression systems and in one laboratory and (iii) evaluate their vaccine efficacy using a single immunisation protocol in mice. In addition, we tested the hypothesis that joining protective antigens as a fusion protein or in combination, into a multivalent vaccine, would improve the ability of the vaccine to induce protective immunity. Out of eight vaccine candidates tested in this study, Ov-103, Ov-RAL-2 and Ov-CPI-2M were shown to reproducibly induce protective immunity when administered individually, as fusion proteins or in combination. Although there was no increase in the level of protective immunity induced by combining the antigens into one vaccine, these antigens remain strong candidates for inclusion in a vaccine to control onchocerciasis in humans. Copyright © 2014 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.
Racz, P; Tenner-Racz, K; Luther, B; Buttner, D W; Albiez, E J
Lymph nodes (LN) from 50 patients with generalized onchocerciasis with or without diethylcarbamazine treatment and LN of patients with untreated localized onchocerciasis were studied. Light and electron microscopic examinations and immunostaining (PAP) were performed. In both forms of the disease the majority of microfilariae were degenerated and surrounded either by eosinophils or macrophages. In addition increased number of mast cells and plasma cells was observed. A direct contact between eosinophils and microfilariae, degranulation of eosinophils and free eosinophil granules in the electron dense material around the degenerating microfilariae were registered. The majority of plasma cells produced IgE or IgG. A positive staining for IgE was also present on the surface of mast cells. An extensive hyperplasia of the follicles was a characteristic feature in localized as well as treated generalized onchocerciasis. After anti-IgE staining a heavy intercellular deposition suggesting trapping of immune complexes by dendritic reticular cells developed in the light parts of the germinal centres. Not seldom, IgE producing blast cells were found in the follicles.
Bennuru, Sasisekhar; Cotton, James A.; Ribeiro, Jose M. C.; Grote, Alexandra; Harsha, Bhavana; Holroyd, Nancy; Mhashilkar, Amruta; Molina, Douglas M.; Randall, Arlo Z.; Shandling, Adam D.; Unnasch, Thomas R.; Ghedin, Elodie; Berriman, Matthew
ABSTRACT Onchocerciasis (river blindness) is a neglected tropical disease that has been successfully targeted by mass drug treatment programs in the Americas and small parts of Africa. Achieving the long-term goal of elimination of onchocerciasis, however, requires additional tools, including drugs, vaccines, and biomarkers of infection. Here, we describe the transcriptome and proteome profiles of the major vector and the human host stages (L1, L2, L3, molting L3, L4, adult male, and adult female) of Onchocerca volvulus along with the proteome of each parasitic stage and of its Wolbachia endosymbiont (wOv). In so doing, we have identified stage-specific pathways important to the parasite’s adaptation to its human host during its early development. Further, we generated a protein array that, when screened with well-characterized human samples, identified novel diagnostic biomarkers of O. volvulus infection and new potential vaccine candidates. This immunomic approach not only demonstrates the power of this postgenomic discovery platform but also provides additional tools for onchocerciasis control programs. PMID:27881553
Isam M A Zarroug
Full Text Available The abundance of onchocerciasis vectors affects the epidemiology of disease in Sudan, therefore, studies of vector dynamics are crucial for onchocerciasis control/elimination programs. This study aims to compare the relative abundance, monthly biting-rates (MBR and hourly-based distribution of onchocerciasis vectors in Abu-Hamed and Galabat foci. These seasonally-based factors can be used to structure vector control efforts to reduce fly-biting rates as a component of onchocerciasis elimination programs.A cross-sectional study was conducted in four endemic villages in Abu-Hamed and Galabat foci during two non-consecutive years (2007-2008 and 2009-2010. Both adults and aquatic stages of the potential onchocerciasis vector Simulium damnosum sensu lato were collected following standard procedures during wet and dry seasons. Adult flies were collected using human landing capture for 5 days/month. The data was recorded on handheld data collection sheets to calculate the relative abundance, MBR, and hourly-based distribution associated with climatic factors. The data analysis was carried out using ANOVA and Spearman rank correlation tests.Data on vector surveillance revealed higher relative abundance of S. damnosum s.l. in Abu- Hamed (39,934 flies than Galabat (8,202 flies. In Abu-Hamed, vector populations increased in January-April then declined in June-July until they disappeared in August-October. Highest black fly density and MBR were found in March 2007 (N = 9,444, MBR = 58,552.8 bites/person/month, and March 2010 (N = 2,603, MBR = 16,138.6 bites/person/month while none of flies were collected in August-October (MBR = 0 bites/person/month. In Galabat, vectors increased in September-December, then decreased in February-June. The highest vector density and MBR were recorded in September 2007 (N = 1,138, MBR = 6,828 bites/person/month and September 2010 (N = 1,163, MBR = 6,978 bites/person/month, whereas, none appeared in collection from April to
Jessica A Hess
Full Text Available In some regions in Africa, elimination of onchocerciasis may be possible with mass drug administration, although there is concern based on several factors that onchocerciasis cannot be eliminated solely through this approach. A vaccine against Onchocerca volvulus would provide a critical tool for the ultimate elimination of this infection. Previous studies have demonstrated that immunization of mice with Ov-103 and Ov-RAL-2, when formulated with alum, induced protective immunity. It was hypothesized that the levels of protective immunity induced with the two recombinant antigens formulated with alum would be improved by formulation with other adjuvants known to enhance different types of antigen-specific immune responses.Immunizing mice with Ov-103 and Ov-RAL-2 in conjunction with alum, Advax 2 and MF59 induced significant levels of larval killing and host protection. The immune response was biased towards Th2 with all three of the adjuvants, with IgG1 the dominant antibody. Improved larval killing and host protection was observed in mice immunized with co-administered Ov-103 and Ov-RAL-2 in conjunction with each of the three adjuvants as compared to single immunizations. Antigen-specific antibody titers were significantly increased in mice immunized concurrently with the two antigens. Based on chemokine levels, it appears that neutrophils and eosinophils participate in the protective immune response induced by Ov-103, and macrophages and neutrophils participate in immunity induced by Ov-RAL-2.The mechanism of protective immunity induced by Ov-103 and Ov-RAL-2, with the adjuvants alum, Advax 2 and MF59, appears to be multifactorial with roles for cytokines, chemokines, antibody and specific effector cells. The vaccines developed in this study have the potential of reducing the morbidity associated with onchocerciasis in humans.
Hess, Jessica A; Zhan, Bin; Torigian, April R; Patton, John B; Petrovsky, Nikolai; Zhan, Tingting; Bottazzi, Maria Elena; Hotez, Peter J; Klei, Thomas R; Lustigman, Sara; Abraham, David
In some regions in Africa, elimination of onchocerciasis may be possible with mass drug administration, although there is concern based on several factors that onchocerciasis cannot be eliminated solely through this approach. A vaccine against Onchocerca volvulus would provide a critical tool for the ultimate elimination of this infection. Previous studies have demonstrated that immunization of mice with Ov-103 and Ov-RAL-2, when formulated with alum, induced protective immunity. It was hypothesized that the levels of protective immunity induced with the two recombinant antigens formulated with alum would be improved by formulation with other adjuvants known to enhance different types of antigen-specific immune responses. Immunizing mice with Ov-103 and Ov-RAL-2 in conjunction with alum, Advax 2 and MF59 induced significant levels of larval killing and host protection. The immune response was biased towards Th2 with all three of the adjuvants, with IgG1 the dominant antibody. Improved larval killing and host protection was observed in mice immunized with co-administered Ov-103 and Ov-RAL-2 in conjunction with each of the three adjuvants as compared to single immunizations. Antigen-specific antibody titers were significantly increased in mice immunized concurrently with the two antigens. Based on chemokine levels, it appears that neutrophils and eosinophils participate in the protective immune response induced by Ov-103, and macrophages and neutrophils participate in immunity induced by Ov-RAL-2. The mechanism of protective immunity induced by Ov-103 and Ov-RAL-2, with the adjuvants alum, Advax 2 and MF59, appears to be multifactorial with roles for cytokines, chemokines, antibody and specific effector cells. The vaccines developed in this study have the potential of reducing the morbidity associated with onchocerciasis in humans.
Francesca F Norman
Full Text Available BACKGROUND: The neglected tropical diseases (NTDs cause significant morbidity and mortality worldwide. Due to the growth in international travel and immigration, NTDs may be diagnosed in countries of the western world, but there has been no specific focus in the literature on imported NTDs. METHODS: Retrospective study of a cohort of immigrants and travelers diagnosed with one of the 13 core NTDs at a Tropical Medicine Referral Unit in Spain during the period April 1989-December 2007. Area of origin or travel was recorded and analyzed. RESULTS: There were 6168 patients (2634 immigrants, 3277 travelers and 257 VFR travelers in the cohort. NTDs occurred more frequently in immigrants, followed by VFR travelers and then by other travelers (p<0.001 for trend. The main NTDs diagnosed in immigrants were onchocerciasis (n = 240, 9.1% acquired mainly in sub-Saharan Africa, Chagas disease (n = 95, 3.6% in immigrants from South America, and ascariasis (n = 86, 3.3% found mainly in immigrants from sub-Saharan Africa. Most frequent NTDs in travelers were: schistosomiasis (n = 43, 1.3%, onchocerciasis (n = 17, 0.5% and ascariasis (n = 16, 0.5%, and all were mainly acquired in sub-Saharan Africa. The main NTDs diagnosed in VFR travelers were onchocerciasis (n = 14, 5.4%, and schistosomiasis (n = 2, 0.8%. CONCLUSIONS: The concept of imported NTDs is emerging as these infections acquire a more public profile. Specific issues such as the possibility of non-vectorial transmission outside endemic areas and how some eradication programmes in endemic countries may have an impact even in non-tropical western countries are addressed. Recognising NTDs even outside tropical settings would allow specific prevention and control measures to be implemented and may create unique opportunities for research in future.
D'Ambrosio, Michael V; Bakalar, Matthew; Bennuru, Sasisekhar; Reber, Clay; Skandarajah, Arunan; Nilsson, Lina; Switz, Neil; Kamgno, Joseph; Pion, Sébastien; Boussinesq, Michel; Nutman, Thomas B; Fletcher, Daniel A
Parasitic helminths cause debilitating diseases that affect millions of people in primarily low-resource settings. Efforts to eliminate onchocerciasis and lymphatic filariasis in Central Africa through mass drug administration have been suspended because of ivermectin-associated serious adverse events, including death, in patients infected with the filarial parasite Loa loa. To safely administer ivermectin for onchocerciasis or lymphatic filariasis in regions co-endemic with L. loa, a strategy termed "test and (not) treat" has been proposed whereby those with high levels of L. loa microfilariae (>30,000/ml) that put them at risk for life-threatening serious adverse events are identified and excluded from mass drug administration. To enable this, we developed a mobile phone-based video microscope that automatically quantifies L. loa microfilariae in whole blood loaded directly into a small glass capillary from a fingerprick without the need for conventional sample preparation or staining. This point-of-care device automatically captures and analyzes videos of microfilarial motion in whole blood using motorized sample scanning and onboard motion detection, minimizing input from health care workers and providing a quantification of microfilariae per milliliter of whole blood in under 2 min. To validate performance and usability of the mobile phone microscope, we tested 33 potentially Loa-infected patients in Cameroon and confirmed that automated counts correlated with manual thick smear counts (94% specificity; 100% sensitivity). Use of this technology to exclude patients from ivermectin-based treatment at the point of care in Loa-endemic regions would allow resumption/expansion of mass drug administration programs for onchocerciasis and lymphatic filariasis in Central Africa. Copyright © 2015, American Association for the Advancement of Science.
Full Text Available Introduction. Cataracts cause about 50% of world blindness. There is little likelihood of effective prevention becoming available in the next few years and so the only treatment will remain surgical. For many of the other major causes of world blindness, like trachoma, xerophthalmia and onchocerciasis, the remedy is community-based, not hospital-based, and requires prevention rather than treatment. The prevalence of blinding cataract will only increase as people live longer, so cataract will continue to be, by far, the most important treatable cause of blindness.
Infectious diseases of the skin have become rarer in industrialized nations, but they still affect a considerable part of the population in tropical regions. Skin diseases induced by protozoa, worms and ectoparasites are among the 17 "neglected tropical diseases" defined by the WHO (leishmaniasis, dracunculiasis, lymphatic filariasis, onchocerciasis). Skin symptoms in travellers returning from the tropics may challenge dermatologists in Germany regarding differential diagnostic assessment and therapy. Among the 12 most frequent skin diseases in travellers are cutaneous larva migrans, leishmaniasis and myiasis. In this review, diagnosis, treatment and prevention of some the most relevant tropical dermatoses due to protozoa, worms and ectoparasites are discussed.
Kobylinski, Kevin C; Sylla, Massamba; Chapman, Phillip L; Sarr, Moussa D; Foy, Brian D
Ivermectin mass drug administration (MDA) to humans is used to control onchocerciasis and lymphatic filariasis. Recent field studies have shown an added killing effect of ivermectin MDA against malaria vectors. We report that ivermectin MDA reduced the proportion of Plasmodium falciparum infectious Anopheles gambiae sensu stricto (s.s.) in treated villages in southeastern Senegal. Ivermectin MDA is a different delivery method and has a different mode of action from current malaria control agents. It could be a powerful and synergistic new tool to reduce malaria transmission in regions with epidemic or seasonal malaria transmission, and the prevalence and intensity of neglected tropical diseases.
Sunita B. Chhaiya
Full Text Available Ivermectin is an antiparasitic drug with a broad spectrum of activity, high efﬁcacy as well as a wide margin of safety. It belongs to the family of avermectins. It binds to glutamate-gated chloride iron channels, which are present in invertebrate nerve and muscle cells, and causes the paralysis and death of the parasite. Ivermectin is approved by the US Food and Drug Administration, and used worldwide to treat patients with onchocerciasis and strongyloidiasis. It is also used against a wide range of endoparasites (nematodes and ectoparasites (insects, acarine of animals and humans. [Int J Basic Clin Pharmacol 2012; 1(3.000: 132-139
Toledo, Chelsea E; Jacobson, Julie; Wainwright, Emily C; Ottesen, Eric A; Lammie, Patrick J
While global programs targeting the control or elimination of five of the neglected tropical diseases (NTDs)-lymphatic filariasis, onchocerciasis, soil-transmitted helminthiasis, schistosomiasis and trachoma-are well underway, they still face many operational challenges. Because of the urgency of 2020 program targets, the Bill & Melinda Gates Foundation and the U.S. Agency for International Development devised a novel rapid research response (RRR) framework to engage national programs, researchers, implementers and WHO in a Coalition for Operational Research on NTDs. After 2 years, this effort has succeeded as an important basis for the research response to programmatic challenges facing NTD programs.
Crainey, James L; Silva, Túllio R R da; Encinas, Fernando; Marín, Michel A; Vicente, Ana Carolina P; Luz, Sérgio L B
We report here the first complete mitochondria genome of Onchocerca volvulus from a focus outside of Africa. An O. volvulus mitogenome from the Brazilian Amazonia focus was obtained using a combination of high-throughput and Sanger sequencing technologies. Comparisons made between this mitochondrial genome and publicly available mitochondrial sequences identified 46 variant nucleotide positions and suggested that our Brazilian mitogenome is more closely related to Cameroon-origin mitochondria than West African-origin mitochondria. As well as providing insights into the origins of Latin American onchocerciasis, the Brazilian Amazonia focus mitogenome may also have value as an epidemiological resource.
Definiability of combinatorial functions and their linear recurrence relationships within a polylogarithmic triangularizable matrix employing surjective bilipschitz functions and other isomorphisms of metric spaces for forecasting seasonal endemic onchoc
Full Text Available In this research,prevalence values based on Monthly Biting Rates (MBR were employed as aresponse variable in a Poisson probability model framework for quantitativelyregressing multiple georefernced explanatory environmental-related explanatorycovariates of seasonally-sampled larval habitat of Similium damnosum s.l.ablack fly vector of Onchocerciasis in ariverine study site in Burkina Faso. Results from both a Poisson and then anegative binomial (i.e., a Poisson random variable with a gamma distrustedmean revealed that the covariates rendered from the model were significant,but furnished virtually no predictive power for mapping endemic transmissionzones. Inclusion of indicator variables denoting the time sequence and thelocational spatial structure was then articulated with Thiessen polygons whichalso failed to reveal meaningful covariates. Thereafter, a spatiotemporalautocorrelation analyses was performed and an Autoregressive Integrated MovingAverage (ARIMA model was constructed which revealed a prominent first-ordertemporal autoregressive structure in the sampled covariate coefficients. Arandom effects term was then specified which included a specific intercept termthat was a random deviation from the overall intercept term based on a drawfrom a normal frequency distribution. The specification revealed a non-constantmean across the riverine study site. This random intercept represented thecombined effect of all omitted covariates that caused the sampled georeferencedriverine –based villages at the study site to be more prone to onchocerciasisbased on regressed seasonal prevalence rates. Additionally, inclusion of arandom intercept assumed random heterogeneity in the propensity or, underlyingrisk of onchocerciasis which persisted throughout the entire duration of thetime sequence under study. This random effects term displayed serialcorrelation, and conformed closely to a bell-shaped curve. The model’s varianceimplied a substantial
Newland, H S; White, A T; Greene, B M; D'Anna, S A; Keyvan-Larijani, E; Aziz, M A; Williams, P N; Taylor, H R
Ivermectin has shown promise as a potentially safe and effective microfilaricidal drug for the treatment of onchocerciasis. Several limited studies have shown it to have fewer side effects, especially ocular complications, than the currently available drug, diethylcarbamazine. The detailed ocular findings in 200 moderately to heavily infected Liberians who were enrolled in a safety and dose-finding study are presented. They received either 0, 100, 150, or 200 micrograms/kg of ivermectin and were followed up for 12 months. In clinical studies so far carried out ivermectin in a dose of 100, 150, or 200 micrograms/kg has not been associated with any major adverse reactions nor were there any sight-threatening effects even in the presence of severe ocular disease. Each of these doses significantly reduced the ocular microfilaria load for at least 12 months when compared with either the placebo (p less than 0.05) or pretreatment values (p less than 0.001). However, the 100 and 150 micrograms/kg doses caused fewer minor side effects than the higher dose. These results confirm that ivermectin in a single oral dose may be a safe and effective microfilaricidal drug for the treatment of onchocerciasis and that it appears to be free of major ocular side effects.
Mario A Rodríguez-Pérez
Full Text Available BACKGROUND: Human landing collections are currently the standard method for collecting onchocerciasis vectors in Africa and Latin America. As part of the efforts to develop a trap to replace human landing collections for the monitoring and surveillance of onchocerciasis transmission, comprehensive evaluations of several trap types were conducted to assess their ability to collect Simulium ochraceum sensu lato, one of the principal vectors of Onchocerca volvulus in Latin America. METHODOLOGY/PRINCIPAL FINDINGS: Diverse trap designs with numerous modifications and bait variations were evaluated for their abilities to collect S. Ochraceum s.l. females. These traps targeted mostly host seeking flies. A novel trap dubbed the "Esperanza window trap" showed particular promise over other designs. When baited with CO2 and BG-lure (a synthetic blend of human odor components a pair of Esperanza window traps collected numbers of S. Ochraceum s.l. females similar to those collected by a team of vector collectors. CONCLUSIONS/SIGNIFICANCE: The Esperanza window trap, when baited with chemical lures and CO2 can be used to collect epidemiologically significant numbers of Simulium ochraceum s.l., potentially serving as a replacement for human landing collections for evaluation of the transmission of O. volvulus.
Evans, D; McFarland, D; Adamani, W; Eigege, A; Miri, E; Schulz, J; Pede, E; Umbugadu, C; Ogbu-Pearse, P; Richards, F O
Onchocerciasis, lymphatic filariasis (LF), schistosomiasis and soil transmitted, helminthiasis (STH) are all co-endemic in Nigeria. Annual mass drug administration (MDA) with ivermectin (for onchocerciasis), albendazole (for STH and with ivermectin for LF) and praziquantel (for schistosomiasis) is the WHO-recommended treatment strategy for preventive chemotherapy. Separate delivery rounds for distribution of these drugs have been the usual approach to MDA. All three drugs, however, have now been shown to be clinically and programmatically safe for co-administration with what has come to be known as triple drug administration (TDA). We examined the cost savings of converting from separate delivery rounds to TDA in two states in Nigeria. In 2008, eight local government areas received a single round of ivermectin with albendazole followed at least 1 week later by a single round of praziquantel to school-aged children. The following year, a single round was administered with TDA. The number of treated individuals was essentially unchanged during both years (1,301,864 in 2008 and 1,297,509 in 2009) and no change in adverse events was reported. The total programmatic costs for the MDA, not including drug and overhead costs, reduced by 41% from $123,624 to $72,870. Cost savings were limited in larger populations due to economies of scale. TDA is recommended for mature MDA.
Hopkins, Adrian D
Programmes to control onchocerciasis have been ongoing for over 40 years. What was once a devastating blinding and disabling disease, particularly in West Africa, has largely been eliminated at least as a public health problem. Efforts continue to eliminate the transmission of the disease. However, as the elimination agenda has developed so have efforts to control/eliminate other neglected tropical diseases (NTDs). The African Programme for Onchocerciasis Control will close at the end of 2015. There has been considerable discussion as to what should replace it and the World Health Organization Africa Region has been consulting widely during the first part of 2015 and has established a new project framework that will be presented to a wider group of stakeholders to mobilise support with the aim of the coordination of NTD activities in the region. This will be called the Expanded Special Project for Elimination of Neglected Tropical Diseases (ESPEN). This will put the countries in the driving seat but offer technical advice, capacity building and financial support, where needed, to enable countries to implement their NTD Master Plans, and also to implement recommendations of the Regional Programme Review Group. An NTD forum will be held periodically to consult with stakeholders.
Convit, Jacinto; Schuler, Harland; Borges, Rafael; Olivero, Vimerca; Domínguez-Vázquez, Alfredo; Frontado, Hortencia; Grillet, María E
Onchocerciasis is caused by Onchocerca volvulus and transmitted by Simulium species (black flies). In the Americas, the infection has been previously described in 13 discrete regional foci distributed among six countries (Brazil, Colombia, Ecuador, Guatemala, Mexico and Venezuela) where more than 370,000 people are currently considered at risk. Since 2001, disease control in Venezuela has relied on the mass drug administration to the at-risk communities. This report provides empirical evidence of interruption of Onchocerca volvulus transmission by Simulium metallicum in 510 endemic communities from two Northern foci of Venezuela, after 10-12 years of 6-monthly Mectizan (ivermectin) treatment to all the eligible residents. In-depth entomologic and epidemiologic surveys were serially conducted from 2001-2012 in selected (sentinel and extra-sentinel) communities from the North-central (NC) and North-east (NE) onchocerciasis foci of Venezuela in order to monitor the impact of ivermectin treatment. From 2007-2009, entomological indicators in both foci confirmed that 0 out of 112,637 S. metallicum females examined by PCR contained L3 infection in insect heads. The upper bound of the 95% confidence intervals of the infective rate of the vector reached values below 1% by 2009 (NC) and 2012 (NE). Additionally, after 14 (NC) and 22 (NE) rounds of treatment, the seasonal transmission potential (±UL CIs) of S. metallicum was under the critical threshold of 20 L3 per person per season. Serological analysis in school children Venezuela.
Udensi K. Udensi & A.F. Fagbenro-Beyioku
Full Text Available Background & objectives: Human and livestock African trypanosomiasis, otherwise known as sleeping sickness,is a neglected tropical disease of public health importance in west and central Africa. In view of the adverse sideeffects of the antitrypanosomal drugs, the relatively few side effects observed in ivermectin use, and becauseboth onchocerciasis and typanosomiasis occur in overlapping foci in Africa, it would be desirable if the ivermectinthat has been used successfully on onchocerciasis management could also be used in the control and treatmentof trypanosomiasis.Method: In this study, prophylactic and therapeutic effects of ivermectin (Mectizan were investigated in albinomice infected with a Nigerian strain of Trypanosoma brucei brucei.Results: A 300 μg/ml/kg dose had the most effective impact because it showed the highest mean survival time of12 days in both the treatment and prophylactic groups of mice. This dose also enhanced the defence capacity ofthe treated groups. It also had positive influence on the packed cell volume (PCV and the state of anaemia inthe trypanosome infected mice, hence, improving their survivability.Interpretation & conclusions: Our report indicates that using the 300 μg/ml/kg dose of ivermectin increases themean survival period from 5 to 12 days. This suggests that ivermectin could be possibly used in the treatment oftrypanosomiasis. Further studies will be required to show whether proper treatment may entail a single dose, asused in this study; an increased number of doses, or combinations with other drugs.
Cotton, James A.; Bennuru, Sasisekhar; Grote, Alexandra; Harsha, Bhavana; Tracey, Alan; Beech, Robin; Doyle, Stephen R.; Dunn, Matthew; Dunning Hotopp, Julie C.; Holroyd, Nancy; Kikuchi, Taisei; Lambert, Olivia; Mhashilkar, Amruta; Mutowo, Prudence; Nursimulu, Nirvana; Ribeiro, Jose M. C.; Rogers, Matthew B.; Stanley, Eleanor; Swapna, Lakshmipuram S.; Tsai, Isheng J.; Unnasch, Thomas R.; Voronin, Denis; Parkinson, John; Nutman, Thomas B.; Ghedin, Elodie; Berriman, Matthew; Lustigman, Sara
Human onchocerciasis is a serious neglected tropical disease caused by the filarial nematode Onchocerca volvulus that can lead to blindness and chronic disability. Control of the disease relies largely on mass administration of a single drug, and the development of new drugs and vaccines depends on a better knowledge of parasite biology. Here, we describe the chromosomes of O. volvulus and its Wolbachia endosymbiont. We provide the highest-quality sequence assembly for any parasitic nematode to date, giving a glimpse into the evolution of filarial parasite chromosomes and proteomes. This resource was used to investigate gene families with key functions that could be potentially exploited as targets for future drugs. Using metabolic reconstruction of the nematode and its endosymbiont, we identified enzymes that are likely to be essential for O. volvulus viability. In addition, we have generated a list of proteins that could be targeted by Federal-Drug-Agency-approved but repurposed drugs, providing starting points for anti-onchocerciasis drug development. PMID:27869790
Rodríguez-Pérez, Mario A.; Adeleke, Monsuru A.; Burkett-Cadena, Nathan D.; Garza-Hernández, Javier A.; Reyes-Villanueva, Filiberto; Cupp, Eddie W.; Toé, Laurent; Salinas-Carmona, Mario C.; Rodríguez-Ramírez, Américo D.; Katholi, Charles R.; Unnasch, Thomas R.
Background Human landing collections are currently the standard method for collecting onchocerciasis vectors in Africa and Latin America. As part of the efforts to develop a trap to replace human landing collections for the monitoring and surveillance of onchocerciasis transmission, comprehensive evaluations of several trap types were conducted to assess their ability to collect Simulium ochraceum sensu lato, one of the principal vectors of Onchocerca volvulus in Latin America. Methodology/Principal Findings Diverse trap designs with numerous modifications and bait variations were evaluated for their abilities to collect S. Ochraceum s.l. females. These traps targeted mostly host seeking flies. A novel trap dubbed the “Esperanza window trap” showed particular promise over other designs. When baited with CO2 and BG-lure (a synthetic blend of human odor components) a pair of Esperanza window traps collected numbers of S. Ochraceum s.l. females similar to those collected by a team of vector collectors. Conclusions/Significance The Esperanza window trap, when baited with chemical lures and CO2 can be used to collect epidemiologically significant numbers of Simulium ochraceum s.l., potentially serving as a replacement for human landing collections for evaluation of the transmission of O. volvulus. PMID:24116169
Colebunders, R; Post, R; O'Neill, S; Haesaert, G; Opar, B; Lakwo, T; Laudisoit, A; Hendy, A
We aim to review the current epidemiology of nodding syndrome (NS) and discuss relevant gaps in research. NS and convulsive epilepsy of unknown aetiology are clustered within the same villages and families in onchocerciasis-endemic areas. They are therefore potentially different clinical expressions of the same disease. It has been difficult to perform full autopsies on NS patients who die in remote villages. Adequate fixation of tissue immediately after death is critical for the examination of brain tissue. Therefore, post-mortem transsphenoidal brain biopsies, performed immediately after death by trained nurses, will provide the best option for obtaining tissue for analysis. We suspect that certain blackflies in onchocerciasis-endemic areas may transmit a novel pathogen that could cause NS and epilepsy. This is supported by a recent drop in the number of new NS cases coinciding with vector control activities aimed at reducing blackfly populations in northern Uganda. We propose that metagenomic studies of human samples, blackflies and microfilariae are conducted to screen for pathogens, and that a clinical trial is planned to evaluate the impact of larviciding against NS and epilepsy epidemics. © 2014 John Wiley & Sons Ltd.
Thiele, Elizabeth A; Cama, Vitaliano A; Lakwo, Thomson; Mekasha, Sindeaw; Abanyie, Francisca; Sleshi, Markos; Kebede, Amha; Cantey, Paul T
Microscopic evaluation of skin biopsies is the monitoring and evaluation (M and E) method currently used by multiple onchocerciasis elimination programs in Africa. However, as repeated mass drug administration suppresses microfilarial loads, the sensitivity and programmatic utility of skin snip microscopy is expected to decrease. Using a pan-filarial real-time polymerase chain reaction with melt curve analysis (qPCR-MCA), we evaluated 1) the use of a single-step molecular assay for detecting and identifying Onchocerca volvulus microfilariae in residual skin snips and 2) the sensitivity of skin snip microscopy relative to qPCR-MCA. Skin snips were collected and examined with routine microscopy in hyperendemic regions of Uganda and Ethiopia (N= 500 each) and "residual" skin snips (tissue remaining after induced microfilarial emergence) were tested with qPCR-MCA. qPCR-MCA detected Onchocerca DNA in 223 residual snips: 139 of 147 microscopy(+) and 84 among microscopy(-) snips, suggesting overall sensitivity of microscopy was 62.3% (139/223) relative to qPCR-MCA (75.6% in Uganda and 28.6% in Ethiopia). These findings demonstrate the insufficient sensitivity of skin snip microscopy for reliable programmatic monitoring. Molecular tools such as qPCR-MCA can augment sensitivity and provide diagnostic confirmation of skin biopsies and will be useful for evaluation or validation of new onchocerciasis M and E tools.
Despite lack of supporting evidence from epidemiologic studies and/or confirmed case reports over the last 30 years, maps in non-specialist works on tropical medicine as well as in documents from specialized organizations (e.g. WHO) systematically include Congo and Gabon, two French-speaking countries, within the zone of endemic filariasis due to Wuchereria bancrofti. One certainty is that no cases were found in field studies carried out in these countries in the late 1970s and 1980s but unfortunately published only in French. Studies that we carried out in the Congo between 1982 and 1987 as part of the National Project on Onchocerciasis and Other Filarioses confirmed the presence of four types of human filariasis: onchocerciasis, loaiasis filarioses caused by Mansonella perstans and M. streptocerca. However, there were no confirmed cases of lymphatic filariosis (bancroftosis). Hopefully the WHO program aimed at the elimination of lymphatic filariasis as a public health problem will provide up-to-date data on the distribution and endemicity of filariasis in Central Africa. Achievement of this objective will depend not only on carrying out new field studies but also on taking into account past studies published in languages other than Shakespeare's.
Ortega, M; Oliver, M; Ramírez, A
In Guatemala, there is no doubt about the participation of Simulium ochraceum as vector of Onchocerciasis. However, in Mexico practically there are not studies focussed to determine the role of this species in the transmission. The objective of the present investigation was to determine which of the 3 species of Simulium founded in the Soconusco region of Chiapas, is the main, and which were secondary in the transmission of Onchocerciasis in that area. The locality of Morelos, in the Huixtla "municipio" of Chiapas, localized a 1200 meters over the sea level (mosl) were selected to carried out the present study. According to own parasitological studies, this locality is considered as highly endemic (more than 66% prevalence). From March 1979 to March, 1981, we performed captures of Simulium sp caught on human bait. Quantitative studies and of transmission potentials were also performed. The following results were obtained: a) Absolute black flies densities (nulliparous and pariparous) and infected black flies (with L1 and L2 larvae): S. ochraceum, S. metallicum and S. callidum, in that order was the distribution of densities. Infected black flies were obtained in the 3 species. However, in despite of an irregular distribution in all the year, it was possible to identify 2 peaks of maximum infection of S. ochraceum in March, 1979 and March 1981. b) Monthly bite densities and infective bites.(ABSTRACT TRUNCATED AT 250 WORDS)
Müllner, A; Helfer, A; Kotlyar, D; Oswald, J; Efferth, T
Neglected helminthic diseases cause many social, economic and health care challenges in developing countries. The high number of patients suffering from these parasitic infections and the lack of sufficient treatment options represent severe problems. Research on new drugs and therapies to meet this urgent requirement has to be intensified. This review focuses on infections caused by four helminthic parasites, which have been declared as neglected diseases by the World Health Organization: namely drancunculiasis, lymphatic filariasis, onchoceriasis, and schistosomiasis. They show a considerable overlap in their world-wide prevalence and treatment strategies. Nevertheless, treatment is not without complications. The most efficient lymphatic filariasis drug, diethylcarbamazine, causes severe adverse effects in onchocerciasis patients and completely fails in the treatment of drancunculiasis. In this review, we discuss these incongruities at the molecular and cellular level. Furthermore, established or investigational drug combination regimens are highlighted. In the past years, progress has been made in the area of schistosomiasis and onchocerciasis. The molecular biology of underlying mechanisms, signalling pathways and related targets affected by drug therapy are discussed in detail. Finally, successful treatment strategies and remaining future challenges are summarized.
Sharma, Raman; Al Jayoussi, Ghaith; Tyrer, Hayley E; Gamble, Joanne; Hayward, Laura; Guimaraes, Ana F; Davies, Jill; Waterhouse, David; Cook, Darren A N; Myhill, Laura J; Clare, Rachel H; Cassidy, Andrew; Steven, Andrew; Johnston, Kelly L; Ford, Louise; Turner, Joseph D; Ward, Stephen A; Taylor, Mark J
Lymphatic filariasis and onchocerciasis are parasitic helminth diseases, which cause severe morbidities such as elephantiasis, skin disease and blindness, presenting a major public health burden in endemic communities. The anti-Wolbachia consortium (A·WOL: http://www.a-wol.com/) has identified a number of registered antibiotics that target the endosymbiotic bacterium, Wolbachia, delivering macrofilaricidal activity. Here we use pharmacokinetics/pharmacodynamics (PK/PD) analysis to rationally develop an anti-Wolbachia chemotherapy by linking drug exposure to pharmacological effect. We compare the pharmacokinetics and anti-Wolbachia efficacy in a murine Brugia malayi model of minocycline versus doxycycline. Doxycycline exhibits superior PK in comparison to minocycline resulting in a 3-fold greater exposure in SCID mice. Monte-Carlo simulations confirmed that a bi-daily 25-40 mg/Kg regimen is bioequivalent to a clinically effective 100-200 mg/day dose for these tetracyclines. Pharmacodynamic studies showed that minocycline depletes Wolbachia more effectively than doxycycline (99.51% vs. 90.35%) after 28 day 25 mg/Kg bid regimens with a more potent block in microfilarial production. PK/PD analysis predicts that minocycline would be expected to be 1.7 fold more effective than doxycycline in man despite lower exposure in our infection models. Our findings warrant onward clinical investigations to examine the clinical efficacy of minocycline treatment regimens against lymphatic filariasis and onchocerciasis.
Ejere, Henry OD; Schwartz, Ellen; Wormald, Richard; Evans, Jennifer R
Background It is believed that ivermectin (a microfilaricide) could prevent blindness due to onchocerciasis. However, when given to everyone in communities where onchocerciasis is common, the effects of ivermectin on lesions affecting the eye are uncertain and data on whether the drug prevents visual loss are unclear. Objectives The aim of this review was to assess the effectiveness of ivermectin in preventing visual impairment and visual field loss in onchocercal eye disease. The secondary aim was to assess the effects of ivermectin on lesions affecting the eye in onchocerciasis. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 3), MEDLINE (January 1950 to April 2012), EMBASE (January 1980 to April 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 2 April 2012. Selection criteria We included randomised controlled trials with at least one year of follow-up comparing ivermectin with placebo or no treatment. Participants in the trials were people normally resident in endemic onchocercal communities with or without one or more characteristic signs of ocular onchocerciasis. Data collection and analysis Two review authors independently extracted data and assessed trial quality. We contacted study authors for additional information. As trials varied in design and setting, we were unable to perform a meta-analysis. Main results The review included four trials: two small studies (n = 398) in which people with onchocercal infection were given one dose of ivermectin or placebo and followed up for one year; and two larger community-based studies (n = 4941) whereby all individuals in
Peter D Burbelo
Full Text Available BACKGROUND: Onchocerciasis, an infection caused by the filarial nematode Onchocerca volvulus, is a major public health concern. Given the debilitating symptoms associated with onchocerciasis and concerns about recrudescence in areas of previous onchocerciasis control, more efficient tools are needed for diagnosis and monitoring of control measures. We investigated whether luciferase immunoprecipitation systems (LIPS may be used as a more rapid, specific, and standardized diagnostic assay for Onchocerca volvulus infection. METHODS: Four recombinantly produced Onchocerca volvulus antigens (Ov-FAR-1, Ov-API-1, Ov-MSA-1 and Ov-CPI-1 were tested by LIPS on a large cohort of blinded sera comprised of both uninfected controls and patients with a proven parasitic infection including Onchocerca volvulus (Ov, Wuchereria bancrofti (Wb, Loa loa (Ll, Strongyloides stercoralis (Ss, and with other potentially cross-reactive infections. In addition to testing all four Ov antigens separately, a mixture that tested all four antigens simultaneously was evaluated in the standard 2-hour incubation format as well as in a 15-minute rapid LIPS format. FINDINGS: Antibody responses to the four different Ov antigens allowed for unequivocal differentiation between Ov-infected and uninfected control sera with 100% sensitivity and 100% specificity. Analysis of the antibody titers to each of these four antigens in individual Ov-infected sera revealed that they were markedly different and did not correlate (r(S = -0.11 to 0.58; P = 0.001 to 0.89 to each other. Compared to Ov-infected sera, patients infected with Wb, Ll, Ss, and other conditions had markedly lower geometric mean antibody titers to each of the Ov 4 antigens (P<0.0002 for each antigen. The simplified method of using a mixture of the 4 Ov antigens simultaneously in the standard format or a quick 15-minute format (QLIPS showed 100% sensitivity and 100% specificity in distinguishing the Ov-infected sera from the
Joseph D Turner
Full Text Available BACKGROUND: The risk of severe adverse events following treatment of onchocerciasis with ivermectin in areas co-endemic with loiasis currently compromises the development of control programmes and the treatment of co-infected individuals. We therefore assessed whether doxycycline treatment could be used without subsequent ivermectin administration to effectively deliver sustained effects on Onchocerca volvulus microfilaridermia and adult viability. Furthermore we assessed the safety of doxycycline treatment prior to ivermectin administration in a subset of onchocerciasis individuals co-infected with low to moderate intensities of Loa loa microfilaraemia. METHODS: A double-blind, randomized, field trial was conducted of 6 weeks of doxycycline (200 mg/day alone, doxycycline in combination with ivermectin (150 microg/kg at +4 months or placebo matching doxycycline + ivermectin at +4 months in 150 individuals infected with Onchocerca volvulus. A further 22 individuals infected with O. volvulus and low to moderate intensities of Loa loa infection were administered with a course of 6 weeks doxycycline with ivermectin at +4 months. Treatment efficacy was determined at 4, 12 and 21 months after the start of doxycycline treatment together with the frequency and severity of adverse events. RESULTS: One hundred and four (60.5% participants completed all treatment allocations and follow up assessments over the 21-month trial period. At 12 months, doxycycline/ivermectin treated individuals had lower levels of microfilaridermia and higher frequency of amicrofilaridermia compared with ivermectin or doxycycline only groups. At 21 months, microfilaridermia in doxycycline/ivermectin and doxycycline only groups was significantly reduced compared to the ivermectin only group. 89% of the doxycycline/ivermectin group and 67% of the doxycycline only group were amicrofilaridermic, compared with 21% in the ivermectin only group. O. volvulus from doxycycline groups were
Gooyit, Major; Tricoche, Nancy; Lustigman, Sara; Janda, Kim D
The L3-stage-specific chitinase OvCHT1 has been implicated in the development of Onchocerca volvulus, the causative agent of onchocerciasis. Closantel, a known anthelmintic drug, was previously discovered as a potent and specific OvCHT1 inhibitor. As closantel is also a known protonophore, we performed a simple scaffold modulation to map out the structural features that are relevant for its individual or dual biochemical roles. Furthermore, we present that either OvCHT1 inhibition or protonophoric activity was capable of affecting O. volvulus L3 molting and that the presence of both activities in a single molecule yielded more potent inhibition of the nematode's developmental process.
The L3-stage-specific chitinase OvCHT1 has been implicated in the development of Onchocerca volvulus, the causative agent of onchocerciasis. Closantel, a known anthelmintic drug, was previously discovered as a potent and specific OvCHT1 inhibitor. As closantel is also a known protonophore, we performed a simple scaffold modulation to map out the structural features that are relevant for its individual or dual biochemical roles. Furthermore, we present that either OvCHT1 inhibition or protonophoric activity was capable of affecting O. volvulus L3 molting and that the presence of both activities in a single molecule yielded more potent inhibition of the nematode’s developmental process. PMID:24918716
During my academic career for more than 40 years, I was involved in 18 epidemiological field studies, partially or fully. Among these field studies, four (1. Medical services in remote rural areas in Okinawa, 2. Yusho episode, 3. JICA Onchocerciasis Control Project in Guatemala, and 4. Miyako cohort study in Fukuoka) are introduced in this paper, including the latest situation after the presentation. Through these field works experienced by the author, the following lessons were gained. 1. Strong human reliance between researchers and the targeted population is essential in carrying out epidemiological surveys successfully in the field. 2. Data obtained from the survey should be carefully examined and analyzed so that those data may reflect the real situation.
Soundararajan, C; Nagarajan, K; Arul Prakash, M
Endemicity of onchocerciasis (river blindness) in humans is linked to the location of Simulium spp. (black fly). The distribution of immature stages of Simulium in Sholur, Pykara, Gudalur, Coonoor and Kotagiri streams of the Nilgiris hills of Tamil Nadu was investigated during the months of May and July 2012. Out of these five streams, only Sholur was infested with larval and pupal stages of Simulium spp. Out of six plants collected from various water bodies, larval and pupal stages were found on the leaves and stems of an aquatic plant Nasturtium officinale and on the roots and leaves of Pennisetum glandulosum. The stages of Simulium were observed only during the summer month of May.
Cox, Francis E G
The period 1875-1925 was remarkable in the history of parasitology partly because of the number of significant discoveries made, especially the elucidation of important life cycles, and partly because of the achievements of the clinicians and scientists who made these discoveries. What is remarkable is that so many of these individuals were Scots. Preeminent in this pantheon was Patrick Manson, who not only discovered the mosquito transmission of filarial worms but was instrumental in directly encouraging others to make significant discoveries in the fields of malaria, Guinea worm disease (dracunculiasis), onchocerciasis, loiasis and schistosomiasis and, indirectly, sleeping sickness and leishmaniasis. This chapter describes and discusses the contributions made by Douglas Argyll-Robertson, Donald Blacklock, David Bruce, David Cunningham, Robert Leiper, William Leishman, George Low, Patrick Manson, Muriel Robertson and Ronald Ross together with short biographical notes.
Lupi, Omar; Downing, Christopher; Lee, Michael; Pino, Livia; Bravo, Francisco; Giglio, Patricia; Sethi, Aisha; Klaus, Sidney; Sangueza, Omar P; Fuller, Claire; Mendoza, Natalia; Ladizinski, Barry; Woc-Colburn, Laila; Tyring, Stephen K
In the 21st century, despite increased globalization through international travel for business, medical volunteerism, pleasure, and immigration/refugees into the United States, there is little published in the dermatology literature regarding the cutaneous manifestations of helminth infections. Approximately 17% of travelers seek medical care because of cutaneous disorders, many related to infectious etiologies. This review will focus on the cutaneous manifestations of helminth infections and is divided into 2 parts: part I focuses on nematode infections, and part II focuses on trematode and cestode infections. This review highlights the clinical manifestations, transmission, diagnosis, and treatment of helminth infections. Nematodes are roundworms that cause diseases with cutaneous manifestations, such as cutaneous larval migrans, onchocerciasis, filariasis, gnathostomiasis, loiasis, dracunculiasis, strongyloidiasis, ascariasis, streptocerciasis, dirofilariasis, and trichinosis. Tremadotes, also known as flukes, cause schistosomiasis, paragonimiasis, and fascioliasis. Cestodes (tapeworms) are flat, hermaphroditic parasites that cause diseases such as sparganosis, cysticercosis, and echinococcus.
Wolstenholme, Adrian J; Maclean, Mary J; Coates, Ruby; McCoy, Ciaran J; Reaves, Barbara J
The macrocyclic lactones (MLs) are one of the few classes of drug used in the control of the human filarial infections, onchocerciasis and lymphatic filariasis, and the only one used to prevent heartworm disease in dogs and cats. Despite their importance in preventing filarial diseases, the way in which the MLs work against these parasites is unclear. In vitro measurements of nematode motility have revealed a large discrepancy between the maximum plasma concentrations achieved after drug administration and the amounts required to paralyze worms. Recent evidence has shed new light on the likely functions of the ML target, glutamate-gated chloride channels, in filarial nematodes and supports the hypothesis that the rapid clearance of microfilariae that follows treatment involves the host immune system.
Brattig, Norbert W; Schwohl, Arline; Hoerauf, Achim; Büttner, Dietrich W
Prostaglandins generated by multiple tissue and immune cells exhibit regulatory effects on the vascular and immune systems. Prostaglandin E(2) (PGE(2)), in particular, affects innate as well as adaptive immune mechanisms. We identified PGE(2) in host immune cells adjacent to Onchocerca volvulus in subcutaneous onchocercomas and the affected skin. Using immunohistology, PGE(2) was predominantly detected in infiltrating macrophages but also in plasma cells. Consecutive sections revealed concomitant presence of PGE(2) and transforming growth factor-beta (TGF-beta), representing a second immunoregulative mediator in macrophages and plasma cells. TGF-beta was preferentially observed in the infiltrating macrophages in patients with a generalized hyporeactive onchocerciasis and less in patients with the hyperreactive form. The presence of PGE(2) and TGF-beta in adjoining host cells infiltrating in the onchocercoma and dermis may indicate containment of inflammatory responses that could favour survival of the filarial parasite.
Duvallet, G; Boireau, P
The parasitic diseases discussed elsewhere in this issue of the Scientific and Technical Review are not the only ones to make use of biological vectors (such as mosquitoes or ticks) or mechanical vectors (such as horse flies or Stomoxys flies). The authors discuss two major groups of vector-borne parasitic diseases: firstly, helminthiasis, along with animal filariasis and onchocerciasis, which are parasitic diseases that often take a heavytoll on artiodactylsthroughoutthe world; secondly, parasitic diseases caused by vector-borne protists, foremost of which is bovine besnoitiosis (or anasarca of cattle), which has recently spread through Europe by a dual mode of transmission (direct and by vector). Other protists, such as Plasmodium and Hepatozoon, are also described briefly.
Dissanayake, S; Xu, M; Piessens, W F
By differentially screening an adult Brugia malayi cDNA library with sera from microfilaremic and amicrofilaremic donors infected with Wuchereria bancrofti, we have identified a novel parasite antigen denoted SXP-1. Recombinant SXP-1 filarial antigen is preferentially recognized by sera from microfilaremic persons with bancroftian filariasis and from skin snip-positive patients with onchocerciasis. Antibodies to SXP-1 are restricted to the IgG4 subclass and gradually decline after treatment with diethylcarbamazine. These findings indicate that it may be possible to replace microscopic examination of night blood films with a serological test designed to detect antibodies to a mix of SXP-1 and other suitable antigens for the diagnosis of microfilaremia due to bancroftian filariasis.
Sommerfeld, J; Oduola, A M J
The African continent is disproportionately affected by infectious diseases. Malaria, HIV/AIDS, tuberculosis, and more "neglected" diseases including African trypanosomiasis, Buruli ulcer, leishmaniasis, onchocerciasis and trachoma continue to dramatically impact social and economic development on the continent. Health biotechnologies provide potential to develop effective strategies for the fight against the vicious circle of poverty and infections by helping in the development and improvement of novel affordable drugs, diagnostics and vaccines against these diseases. As the prospects of this emerging biotechnology research and deployment of its products become a reality in Africa, there is a need to consider the ethical, legal and social implications of both the scientific and technological advances and their use in the communities. The article provides a short overview of the potential values of biotechnology, issues involved in its transfer and presents the rationale, design and recommendations of the international workshop/symposium held in April 2005 at the International Institute for Tropical Agriculture (IITA) in Ibadan, Nigeria.
Bari Arfan ul
Full Text Available Background: Physical differences among human populations may lead to variable prevalence of skin disorders in different ethnicities. Skin infections are one of the important curable and largely preventable categories of skin disorders in the communities. Aim: The purpose of the study was to see the patterns of skin infections in black Africans of Sierra Leone and to compare with other ethnic populations. Materials and Methods: Local blacks of all age groups presenting in Dermatology out patient department of Pak Field Hospital (established as a part of UN peacekeeping mission in Sierra Leone were included (from Nov 2004 to Oct 2005. Relevant clinical history and physical examination was done. Laboratory investigations were carried out when indicated. Skin diseases were broadly classified into two major categories i.e., infective and noninfective. Among infective, sexually transmitted infections were again separated. Nonblack settlers in the area and UN troops were not included in the study. Data was recorded and analyzed by Microsoft Excel program. Results: 3011 patients belonging to different local tribes having a variety of skin disorders were seen. Patients were of all ages and both sexes ranging from one month to 73 years of age. The Infective skin disorders were seen in 61.7% patients and most prevalent were superficial fungal infections (41.2% followed by, sexually transmitted infections (9.9% and parasitic infections (6.5%. Bacterial and viral infections were rare and so was the scabies. More than 90% parasitic infections were onchocerciasis with full spectrum of cutaneous manifestations. Conclusion: Pattern of skin infections in blacks varies considerably from other ethnic races. Environmental factors, geographical location and free existence of vector for onchocerciasis in West African region, possibly have a significant influence in this variable prevalence.
Anne L Wilson
Full Text Available Insecticide-treated nets (ITNs are one of the main interventions used for malaria control. However, these nets may also be effective against other vector borne diseases (VBDs. We conducted a systematic review and meta-analysis to estimate the efficacy of ITNs, insecticide-treated curtains (ITCs and insecticide-treated house screening (ITS against Chagas disease, cutaneous and visceral leishmaniasis, dengue, human African trypanosomiasis, Japanese encephalitis, lymphatic filariasis and onchocerciasis.MEDLINE, EMBASE, LILACS and Tropical Disease Bulletin databases were searched using intervention, vector- and disease-specific search terms. Cluster or individually randomised controlled trials, non-randomised trials with pre- and post-intervention data and rotational design studies were included. Analysis assessed the efficacy of ITNs, ITCs or ITS versus no intervention. Meta-analysis of clinical data was performed and percentage reduction in vector density calculated.Twenty-one studies were identified which met the inclusion criteria. Meta-analysis of clinical data could only be performed for four cutaneous leishmaniasis studies which together showed a protective efficacy of ITNs of 77% (95%CI: 39%-91%. Studies of ITC and ITS against cutaneous leishmaniasis also reported significant reductions in disease incidence. Single studies reported a high protective efficacy of ITS against dengue and ITNs against Japanese encephalitis. No studies of Chagas disease, human African trypanosomiasis or onchocerciasis were identified.There are likely to be considerable collateral benefits of ITN roll out on cutaneous leishmaniasis where this disease is co-endemic with malaria. Due to the low number of studies identified, issues with reporting of entomological outcomes, and few studies reporting clinical outcomes, it is difficult to make strong conclusions on the effect of ITNs, ITCs or ITS on other VBDs and therefore further studies be conducted. Nonetheless, it
O'Neill, Maeghan; Ballesteros, Cristina; Tritten, Lucienne; Burkman, Erica; Zaky, Weam I; Xia, Jianguo; Moorhead, Andrew; Williams, Steven A; Geary, Timothy G
The use of microfilaricidal drugs for the control of onchocerciasis and lymphatic filariasis (LF) necessitates prolonged yearly dosing. Prospects for elimination or eradication of these diseases would be enhanced by the availability of a macrofilaricidal drug. Flubendazole (FLBZ), a benzimidazole anthelmintic, is an appealing candidate. FLBZ has demonstrated potent macrofilaricidal effects in a number of experimental rodent models and in one human trial. Unfortunately, FLBZ was deemed unsatisfactory for use in mass drug administration campaigns due to its limited oral bioavailability. A new formulation that enables sufficient bioavailability following oral administration could render FLBZ an effective treatment for onchocerciasis and LF. Identification of drug-derived effects is important in ascertaining a dosage regimen which is predicted to be lethal to the parasite in situ. In previous histological studies, exposure to FLBZ induced damage to tissues required for reproduction and survival at pharmacologically relevant concentrations. However, more precise and quantitative indices of drug effects are needed. This study assessed drug effects using a transcriptomic approach to confirm effects observed histologically and to identify genes which were differentially expressed in treated adult female Brugia malayi. Comparative analysis across different concentrations (1 μM and 5 μM) and durations (48 and 120 h) provided an overview of the processes which are affected by FLBZ exposure. Genes with dysregulated expression were consistent with the reproductive effects observed via histology in our previous studies. This study revealed transcriptional changes in genes involved in embryo development. Additionally, significant downregulation was observed in genes encoding cuticle components, which may reflect changes in developing embryos, the adult worm cuticle or both. These data support the hypothesis that FLBZ acts predominantly on rapidly dividing cells, and provides
Full Text Available The onchocerciasis transmission models EPIONCHO and ONCHOSIM have been independently developed and used to explore the feasibility of eliminating onchocerciasis from Africa with mass (annual or biannual distribution of ivermectin within the timeframes proposed by the World Health Organization (WHO and endorsed by the 2012 London Declaration on Neglected Tropical Diseases (i.e. by 2020/2025. Based on the findings of our previous model comparison, we implemented technical refinements and tested the projections of EPIONCHO and ONCHOSIM against long-term epidemiological data from two West African transmission foci in Mali and Senegal where the observed prevalence of infection was brought to zero circa 2007–2009 after 15–17 years of mass ivermectin treatment. We simulated these interventions using programmatic information on the frequency and coverage of mass treatments and trained the model projections using longitudinal parasitological data from 27 communities, evaluating the projected outcome of elimination (local parasite extinction or resurgence. We found that EPIONCHO and ONCHOSIM captured adequately the epidemiological trends during mass treatment but that resurgence, while never predicted by ONCHOSIM, was predicted by EPIONCHO in some communities with the highest (inferred vector biting rates and associated pre-intervention endemicities. Resurgence can be extremely protracted such that low (microfilarial prevalence between 1% and 5% can be maintained for 3–5 years before manifesting more prominently. We highlight that post-treatment and post-elimination surveillance protocols must be implemented for long enough and with high enough sensitivity to detect possible residual latent infections potentially indicative of resurgence. We also discuss uncertainty and differences between EPIONCHO and ONCHOSIM projections, the potential importance of vector control in high-transmission settings as a complementary intervention strategy, and the
Pion, Sébastien D S; Grout, Lise; Kamgno, Joseph; Nana-Djeunga, Hugues; Boussinesq, Michel
Reduction in Onchocerca volvulus skin microfilarial densities after treatment with ivermectin shows wide between-host variation. Data from two separate studies conducted in Cameroon on onchocerciasis patients treated for the first time with ivermectin were analyzed to identify host factors associated with microfilarial density at different time-points after treatment. In one site (Nkam valley), the dataset included 103 adult males for whom age, number of palpable onchocercal nodules and microfilarial densities on D0 (pre-treatment), D15, D80 and D180 were available. In the other site (Vina valley), analyses were conducted on 965 individuals of both sexes aged 5 years and over; in this dataset, available information included age, gender, exact dose of ivermectin received, onchocerciasis endemicity level in the village of residence and microfilarial densities on D0 and D180. Negative binomial regression models of microfilarial density at the different intervals post-treatment were fitted, using maximum likelihood, with the available independent variables. Gender and age were found to be associated with microfilarial density on D180. The initial microfilarial density influenced post-treatment densities at all the time-points. All other things being equal, microfilarial densities on D180 were higher in individuals harbouring a higher number of nodules or living in communities with high endemicity levels. This study demonstrates that O. volvulus microfilarial density measured after a first treatment with ivermectin, and thus probably the rate of skin repopulation by microfilariae (mf) varies according to several host factors. Should such factors also influence ivermectin efficacy after repeated treatment, then they should be taken into account to determine whether sub-optimal responses to treatment reported from various areas in Africa are actually due to parasite-related factors, particularly to the emergence of resistant populations.
Cho-Ngwa, Fidelis; Monya, Elvis; Azantsa, Boris K; Manfo, Faustin Pascal T; Babiaka, Smith B; Mbah, James A; Samje, Moses
Onchocerciasis is the world's second leading infectious cause of blindness. Its control is currently hampered by the lack of a macrofilaricidal drug and by severe adverse events observed when the lone recommended microfilaricide, ivermectin is administered to individuals co-infected with Loa loa. Therefore, there is the need for a safe and effective macrofilaricidal drug that will be able to cure the infection and break transmission cycles, or at least, an alternative microfilaricide that does not kill L. loa microfilariae (mf). Fourteen extracts from two medicinal plants, Tragia benthami and Piper umbellatum were screened in vitro against Onchocerca ochengi parasite and L. loa mf. Activities of extracts on male worms and microfilariae were assessed by motility reduction, while MTT/Formazan assay was used to assess biochemically the death of female worms. Cytotoxicity and acute toxicity of active extracts were tested on monkey kidney cells and Balb/c mice, respectively. At 500 μg/mL, all extracts showed 100 % activity on Onchocerca ochengi males and microfilariae, while 9 showed 100 % activity on female worms. The methylene chloride extract of Piper umbellatum leaves was the most active on adult male and female worms (IC50s: 16.63 μg/mL and 35.65 μg/mL, respectively). The three most active extracts on Onchocerca ochengi females were also highly active on Loa loa microfilariae, with IC50s of 35.12 - 13.9 μg/mL. Active extracts were generally more toxic to the worms than to cells and showed no acute toxicity to Balb/c mice. Phytochemical screening revealed the presence of saponins, steroids, tannins and flavanoids in the promising extracts. These results unfold potential sources of novel anti-Onchocerca lead compounds and validate the traditional use of the plants in onchocerciasis treatment.
Full Text Available Abstract Background Among ocular vector-borne pathogens, Onchocerca volvulus, the agent of the so-called “river blindness”, affects about 37 million people globally. Other Onchocerca spp. have been sporadically reported as zoonotic agents. Cases of canine onchocerciasis caused by Onchocerca lupi are on the rise in the United States and Europe. Its zoonotic role has been suspected but only recently ascertained in a single case from Turkey. The present study provides further evidence on the occurrence of O. lupi infesting human eyes in two patients from Turkey (case 1 and Tunisia (case 2. The importance of obtaining a correct sample collection and preparation of nematodes infesting human eyes is highlighted. Methods In both cases the parasites were identified with morpho-anatomical characters at the gross examination, histological analysis and anatomical description and also molecularly in case 1. Results The nematode from the first case was obviously O. lupi based on their morphology at the gross examination, histological analysis and anatomical description. In the second case, although the diagnostic cuticular characters were not completely developed, other features were congruent with the identification of O. lupi. Furthermore, the morphological identification was also molecularly confirmed in the Turkish case. Conclusions The results of this study suggest that O. lupi infestation is not an occasional finding but it should be considered in the differential diagnosis of other zoonotic helminths causing eye infestation in humans (e.g., D. immitis and Dirofilaria repens. Both cases came from areas where no cases of canine onchocerciasis were previously reported in the literature, suggesting that an in depth appraisal of the infestation in canine populations is necessary. Physicians and ophthalmologists are advised on how to preserve nematode samples recovered surgically, to allow a definitive, correct etiological diagnosis.
Hotez, Peter J; Strych, Ulrich; Lustigman, Sara; Bottazzi, Maria Elena
Helminth infections are the most common afflictions of humankind, affecting almost every single person living in profound poverty. Through mass drug administration (MDA) we have seen sharp declines in the global prevalence of some helminth infections, including lymphatic filariasis, onchocerciasis, and ascariasis. However, since 1990, there has been no appreciable decrease in the global prevalence of hookworm infection, schistosomiasis, or food-borne trematodiases. Through the activities of a non-profit product development partnerships and two research institutes, a total of five human anthelmintic vaccines for hookworm infection (two) and schistosomiasis (three) have advanced from discovery through manufacture and are now in Phase 1 clinical testing. At least three additional antigens, including two for onchocerciasis and one for schistosomiasis, are also advancing through preclinical development with the intention of moving into the clinic soon. These preventive human anthelmintic vaccines could be used as stand-alone technologies administered to infants as part of the Expanded Program on Immunization (EPI), or together with anthelmintic drugs in programs linked to MDA. Significant hurdles though could hinder the advancement of these vaccines into later-stage clinical and product development and licensure. They include the absence of a major pharma partner (and the resultant access to adjuvants and industrial scale manufacturing expertise), an uncharted roadmap for how to introduce anthelmintic vaccines into appropriate health systems, uncertain global access and regulatory strategies that might need to rely on developing country vaccine manufacturers and national regulatory authorities, and the lack of innovative financing schemes. However, the public health and economic benefits of introducing these vaccines could be massive and therefore deserve international attention and support. Copyright © 2016 Elsevier Ltd. All rights reserved.
Kamgno, Joseph; Nguipdop-Djomo, Patrick; Gounoue, Raceline; Téjiokem, Mathurin; Kuesel, Annette C
Loiasis is a parasitic infection endemic in the African rain forest caused by the filarial nematode Loa loa. Loiasis can be co-endemic with onchocerciasis and/or lymphatic filariasis. Ivermectin, the drug used in the control of these diseases, can induce serious adverse reactions in patients with high L loa microfilaraemia (LLM). A drug is needed which can lower LLM below the level that represents a risk so that ivermectin mass treatment to support onchocerciasis and lymphatic filariasis elimination can be implemented safely. Sixty men and women from a loiasis endemic area in Cameroon were randomized after stratification by screening LLM (≤ 30000, 30001-50000, >50000) to three treatment arms: two doses albendazole followed by 4 doses matching placebo (n = 20), six doses albendazole (n = 20) albendazole or 6 doses matching placebo (n = 20) administered every two months. LLM was measured before each treatment and 14, 18, 21 and 24 months after the first treatment. Monitoring for adverse events occurred three and seven days as well as 2 months after each treatment. None of the adverse events recorded were considered treatment related. The percentages of participants with ≥ 50% decrease in LLM from pre-treatment for ≥ 4 months were 53%, 17% and 11% in the 6-dose, 2-dose and placebo treatment arms, respectively. The difference between the 6-dose and the placebo arm was significant (p = 0.01). The percentages of participants with LLM treatment arms, respectively. The 6-dose regimen reduced LLM significantly, but the reduction was insufficient to eliminate the risk of severe and/or serious adverse reactions during ivermectin mass drug administration in loiasis co-endemic areas.
Full Text Available BACKGROUND: Mali is endemic for all five targeted major neglected tropical diseases (NTDs. As one of the five 'fast-track' countries supported with the United States Agency for International Development (USAID funds, Mali started to integrate the activities of existing disease-specific national control programs on these diseases in 2007. The ultimate objectives are to eliminate lymphatic filariasis, onchocerciasis and trachoma as public health problems and to reduce morbidity caused by schistosomiasis and soil-transmitted helminthiasis through regular treatment to eligible populations, and the specific objectives were to achieve 80% program coverage and 100% geographical coverage yearly. The paper reports on the implementation of the integrated mass drug administration and the lessons learned. METHODOLOGY/PRINCIPAL FINDINGS: The integrated control program was led by the Ministry of Health and coordinated by the national NTD Control Program. The drug packages were designed according to the disease endemicity in each district and delivered through various platforms to eligible populations involving the primary health care system. Treatment data were recorded and reported by the community drug distributors. After a pilot implementation of integrated drug delivery in three regions in 2007, the treatment for all five targeted NTDs was steadily scaled up to 100% geographical coverage by 2009, and program coverage has since been maintained at a high level: over 85% for lymphatic filariasis, over 90% for onchocerciasis and soil-transmitted helminthiasis, around 90% in school-age children for schistosomiasis, and 76-97% for trachoma. Around 10 million people have received one or more drug packages each year since 2009. No severe cases of adverse effects were reported. CONCLUSIONS/SIGNIFICANCE: Mali has scaled up the drug treatment to national coverage through integrated drug delivery involving the primary health care system. The successes and lessons
Full Text Available Ivermectin-based mass drug administration (MDA programs have achieved remarkable success towards the elimination of onchocerciasis and lymphatic filariasis. However, their full implementation has been hindered in Central Africa by the occurrence of ivermectin-related severe adverse events (SAEs in a subset of individuals with high circulating levels of Loa loa microfilariae. Extending MDA to areas with coincident L. loa infection is problematic, and inexpensive point-of-care tests for L. loa are acutely needed. Herein, we present a lateral flow assay (LFA to identify subjects with a serological response to Ll-SXP-1, a specific and validated marker of L. loa. The test was evaluated on serum samples from patients infected with L. loa (n = 109 and other helminths (n = 204, as well as on uninfected controls (n = 77. When read with the naked eye, the test was 94% sensitive for L. loa infection and was 100% specific when sera from healthy endemic and non-endemic controls or from those with S. stercoralis infections were used as the comparators. When sera of patients with O. volvulus, W. bancrofti, or M. perstans were used as the comparators, the specificity of the LFA was 82%, 87%, and 88%, respectively. A companion smartphone reader allowed measurement of the test line intensities and establishment of cutoff values. With a cutoff of 600 Units, the assay sensitivity decreased to 71%, but the specificity increased to 96% for O. volvulus, 100% for W. bancrofti, and 100% for M. perstans-infected individuals. The LFA may find applications in refining the current maps of L. loa prevalence, which are needed to eliminate onchocerciasis and lymphatic filariasis from the African continent.
Armoo, Samuel; Doyle, Stephen R; Osei-Atweneboana, Mike Y; Grant, Warwick N
Wolbachia are intracellular bacteria found in arthropods and several filarial nematode species. The filarial Wolbachia have been proposed to be involved in the immunopathology associated with onchocerciasis. Higher Wolbachia-to-nematode ratios have been reported in the savannah-ecotype compared to the forest-ecotype, and have been interpreted as consistent with a correlation between Wolbachia density and disease severity. However, factors such as geographic stratification and ivermectin drug exposure can lead to significant genetic heterogeneity in the nematode host populations, so we investigated whether Wolbachia copy number variation is also associated with these underlying factors. Genomic DNA was prepared from single adult nematodes representing forest and savannah ecotypes sampled from Togo, Ghana, Côte d'Ivoire and Mali. A qPCR assay was developed to measure the number of Wolbachia genome(s) per nematode genome. Next-generation sequencing (NGS) was also used to measure relative Wolbachia copy number, and independently verify the qPCR assay. Significant variation was observed within the forest (range: 0.02 to 452.99; median: 10.58) and savannah (range: 0.01 to 1106.25; median: 9.10) ecotypes, however, no significant difference between ecotypes (P = 0.645) was observed; rather, strongly significant Wolbachia variation was observed within and between the nine study communities analysed (P = 0.021), independent of ecotype. Analysis of ivermectin-treated and untreated nematodes by qPCR showed no correlation (P = 0.869); however, an additional analysis of a subset of the nematodes by qPCR and NGS revealed a correlation between response to ivermectin treatment and Wolbachia copy number (P = 0.020). This study demonstrates that extensive within and between population variation exists in the Wolbachia content of individual adult O. volvulus. The origin and functional significance of such variation (up to ~ 100,000-fold between worms; ~10 to 100
Full Text Available Control of onchocerciasis as a public health problem in Africa relies on annual mass ivermectin distribution. New tools are needed to achieve elimination of infection. This study determined in a small number of Onchocerca volvulus infected individuals whether moxidectin, a veterinary anthelminthic, is safe enough to administer it in a future large study to further characterize moxidectin's safety and efficacy. Effects on the parasite were also assessed.Men and women from a forest area in South-eastern Ghana without ivermectin mass distribution received a single oral dose of 2 mg (N = 44, 4 mg (N = 45 or 8 mg (N = 38 moxidectin or 150 µg/kg ivermectin (N = 45 with 18 months follow up. All ivermectin and 97%-100% of moxidectin treated participants had Mazzotti reactions. Statistically significantly higher percentages of participants treated with 8 mg moxidectin than participants treated with ivermectin experienced pruritus (87% vs. 56%, rash (63% vs. 42%, increased pulse rate (61% vs. 36% and decreased mean arterial pressure upon 2 minutes standing still after ≥5 minutes supine relative to pre-treatment (61% vs. 27%. These reactions resolved without treatment. In the 8 mg moxidectin and ivermectin arms, the mean±SD number of microfilariae/mg skin were 22.9±21.1 and 21.2±16.4 pre-treatment and 0.0±0.0 and 1.1±4.2 at nadir reached 1 and 3 months after treatment, respectively. At 6 months, values were 0.0±0.0 and 1.6±4.5, at 12 months 0.4±0.9 and 3.4±4.4 and at 18 months 1.8±3.3 and 4.0±4.8, respectively, in the 8 mg moxidectin and ivermectin arm. The reduction from pre-treatment values was significantly higher after 8 mg moxidectin than after ivermectin treatment throughout follow up (p<0.01.The 8 mg dose of moxidectin was safe enough to initiate the large study. Provided its results confirm those from this study, availability of moxidectin to control programmes could help them achieve onchocerciasis elimination
Albiez, E J; Walter, G; Kaiser, A; Ranque, P; Newland, H S; White, A T; Greene, B M; Taylor, H R; Büttner, D W
During chemotherapy trials in hyperendemic onchocerciasis areas in West Africa 15 adult nodule carriers in Liberia and 24 patients in Mali received single doses of ivermectin (150 or 200 micrograms/kg). Nodules were extirpated two, six and ten months after therapy and examined histologically. No macrofilaricidal effect of ivermectin was observed. Two months after therapy, in 93% of all female worms with intrauterine stretched microfilariae nearly all microfilariae were degenerated. The percentage was lower after ten months but still significantly higher than in untreated control groups. Ivermectin did not cause degeneration of the intrauterine coiled microfilariae. But the percentage of the female worms with coiled microfilariae was significantly lower two and ten months after therapy than that in the placebo or untreated control groups. Correspondingly, the percentage of nodules with intact microfilariae in the nodule tissue was also significantly lower throughout the examination period than that of the untreated control groups. There was not observed any effect on the spermatogenesis and spermatozoa were found frequently in the uteri of female worms. Using the method of histology, the long lasting inhibitory effect of a single dose of ivermectin on the intrauterine production of microfilariae could clearly be demonstrated. This proves the value of histology for the assessment of drug effects on adult O. volvulus.
Herrick, Jesica A; Legrand, Fanny; Gounoue, Raceline; Nchinda, Godwin; Montavon, Céline; Bopda, Jean; Tchana, Steve Mbickmen; Ondigui, Bienvenu Etogo; Nguluwe, Konrad; Fay, Michael P; Makiya, Michelle; Metenou, Simon; Nutman, Thomas B; Kamgno, Joseph; Klion, Amy D
Severe adverse reactions have been observed in individuals with Loa loa infection treated with either diethylcarbamazine (DEC), the drug of choice for loiasis, or ivermectin (IVM), which is used in mass drug administration programs for control of onchocerciasis and lymphatic filariasis in Africa. In this study, posttreatment clinical and immunologic reactions were compared following single-dose therapy with DEC or IVM to assess whether these reactions have the same underlying pathophysiology. Twelve patients with loiasis and microfilarial counts single-dose DEC (8 mg/kg) or IVM (200 µg/kg). Clinical and laboratory assessments were performed at 4, 8, 24, 48, and 72 hours and 5, 7, 9, and 14 days posttreatment. Posttreatment adverse events were similar following DEC or IVM, but peaked earlier in subjects who received DEC, consistent with a trend toward more rapid and complete microfilarial clearance in the DEC group. After a transient rise (post-IVM) or fall (post-DEC) in the first 24 hours posttreatment, the eosinophil count rose significantly in both groups, peaking at day 5 in the DEC group and day 9 in the IVM group. Serum interleukin 5 levels and eosinophil activation, as assessed by surface expression of CD69 and serum levels of eosinophil granule proteins, were increased posttreatment in both groups. Despite differences in eosinophil and lymphocyte counts during the first 24 hours posttreatment, the overall pattern of hematologic and immunologic changes suggest that posttreatment reactions following DEC and IVM share a common pathophysiology. NCT01593722.
Full Text Available BACKGROUND: Lymphatic filariasis and onchocerciasis are two chronic diseases mediated by parasitic filarial worms causing long term disability and massive socioeconomic problems. Filariae are transmitted by blood-feeding mosquitoes that take up the first stage larvae from an infected host and deliver it after maturation into infective stage to a new host. After closure of vector control programs, disease control relies mainly on mass drug administration with drugs that are primarily effective against first stage larvae and require many years of annual/biannual administration. Therefore, there is an urgent need for alternative treatment ways, i.e. other effective drugs or vaccines. METHODOLOGY/PRINCIPAL FINDINGS: Using the Litomosoides sigmodontis murine model of filariasis we demonstrate that immunization with microfilariae together with the adjuvant alum prevents mice from developing high microfilaraemia after challenge infection. Immunization achieved 70% to 100% protection in the peripheral blood and in the pleural space and furthermore strongly reduced the microfilarial load in mice that remained microfilaraemic. Protection was associated with the impairment of intrauterine filarial embryogenesis and with local and systemic microfilarial-specific host IgG, as well as IFN-γ secretion by host cells from the site of infection. Furthermore immunization significantly reduced adult worm burden. CONCLUSIONS/SIGNIFICANCE: Our results present a tool to understand the immunological basis of vaccine induced protection in order to develop a microfilariae-based vaccine that reduces adult worm burden and prevents microfilaraemia, a powerful weapon to stop transmission of filariasis.
Monica Cartelle Gestal
Full Text Available Tropical and zoonotic diseases are major problems in developing countries like Ecuador. Poorly designed houses, the high proportion of isolated indigenous population and under developed infrastructure represent a fertile environment for vectors to proliferate. Control campaigns in Ecuador over the years have had varying success, depending on the disease and vectors targeted.In our study we analyse the current situation of some neglected diseases in Ecuador and the efficiency of the control campaigns (by measuring changes in numbers of cases reported that the Ecuadorian government has been running to limit the spread of these infectious and parasitic diseases.Our study reveals that Brucellosis, Chagas Disease, Rabies and Onchocerciasis have been controlled, but small outbreaks are still detected in endemic areas. Leptospirosis and Echinococcosis have been increasing steadily in recent years in Ecuador since the first records. The same increase has been reported world-wide also. Better diagnosis has resulted in a higher number of cases being identified, particularly with regard to the linking of outdoor activities and contact with farm animals as contributing vectors. Improvements in diagnosis are due to regular professional training, implementation of automatized systems, establishing diagnosis protocols and the creation of an epidemiological vigilance network that acts as soon as a case is reported.Control campaigns performed in Ecuador have been successful in recent years, although natural phenomena limit their efficiency. Leptospirosis and Echinococcosis infections remain a growing problem in Ecuador as it is worldwide.
Hagedorn Henry H
Full Text Available Abstract Background Oocyte development was studied in the autogenous black fly, Simulium vittatum (Diptera, Nematocera, a vector of Onchocerca volvulus, the causative agent of onchocerciasis. Results Oocyte growth was nearly linear between adult eclosion and was complete by 72 hours at 21°C. The oocyte became opaque at 14 hours after eclosion indicating the initiation of protein yolk deposition. The accumulation of vitellogenin was measured using SDS-PAGE. The density of the yolk protein bands at about 200 and 65 kDa increased during the first and second days after eclosion. The amount of protein in the 200 kDa band of vitellogenin, determined using densitometry, rapidly increased between 12 and 25 hours after eclosion. Ecdysteroid levels were measured using a competitive ELISA. Ecdysteroid levels increased rapidly and subsequently declined during the first day after eclosion. Conclusion These data show a correlation between the appearance of vitellogenin in the oocyte, and the rise in ecdysteroids. A possible relationship to molting of the nematode, Onchocerca volvulus, is discussed.
Khalfan A Mohammed
Full Text Available BACKGROUND: Public health interventions based on distribution of anthelminthic drugs against lymphatic filariasis (LF, onchocerciasis, soil-transmitted helminthiasis (STH and schistosomiasis have been implemented separately to date. A better use of available resources might be facilitated by a more coordinated approach to control such infections, including the possibility of co-administering the three recommended anthelminthic drugs through a single, large-scale intervention. METHODOLOGY/PRINCIPAL FINDINGS: Ivermectin, albendazole and praziquantel were co-administered to 5,055 children and adults living in areas endemic for LF, STH and schistosomiasis in Zanzibar, United Republic of Tanzania, during a pilot intervention aimed at elucidating and quantifying possible side-effects. Subsequently, these drugs were co-administered to about 700,000 individuals during a countrywide intervention targeting a large part of the total population of Zanzibar. Passive and active surveillance measures carried out during both interventions showed that side-effects attributable to the three drugs given at the same time were mild and self-limiting events. CONCLUSIONS/SIGNIFICANCE: Our data suggest that co-administration of ivermectin, albendazole and praziquantel is safe in areas where lymphatic filariasis, soil-transmitted helminthiasis and schistosomiasis are co-endemic and where several rounds of treatment with one or two drugs have been implemented in the past. Passive surveillance measures, however, should be continued and detection, management and reporting of possible side-effects should be considered a key component of any health intervention administering drugs.
Garner, Amanda L; Gloeckner, Christian; Tricoche, Nancy; Zakhari, Joseph S; Samje, Moses; Cho-Ngwa, Fidelis; Lustigman, Sara; Janda, Kim D
Onchocerciasis, or river blindness, is a neglected tropical disease that affects more than 37 million people worldwide, primarily in Africa and Central and South America. We have disclosed evidence that the larval-stage-specific chitinase, OvCHT1, may be a potential biological target for affecting nematode development. On the basis of screening efforts, closantel, a known anthelmintic drug, was discovered as a potent and highly specific OvCHT1 inhibitor. Originally, closantel's anthelmintic mode of action was believed to rely solely on its role as a proton ionophore; thus, the impact of each of its biological activities on O. volvulus L3 molting was investigated. Structure-activity relationship studies on an active closantel fragment are detailed, and remarkably, by use of a simple salicylanilide scaffold, compounds acting only as protonophores or chitinase inhibitors were identified. From these data, unexpected synergistic protonophore and chitinase inhibition activities have also been found to be critical for molting in O. volvulus L3 larvae.
Gutiérrez-Peña, E J; Knab, J; Büttner, D W
The participation of neutrophil granulocytes in the cellular reaction to skin microfilariae of Onchocerca volvulus was studied by immunohistochemistry. Skin biopsies were obtained from adult Liberian and Ugandan patients with generalized onchocerciasis after exposure to topically applied diethylcarbamazine (DEC) and from untreated patients. After DEC many damaged microfilariae were observed either in dermal infiltrates or in epidermal microabscesses consisting both of neutrophils and eosinophils. Infiltrates and microabscesses contained some intact granulocytes and many neutrophils releasing myeloperoxidase, elastase, lactoferrin, defensin, lysozyme, alpha 1-antitrypsin and alpha 1-antichymotrypsin. Eosinophils discharged peroxidase and cationic proteins. Released granule proteins and remnants of disrupted granulocytes were found on the surface and in close proximity of damaged microfilariae in dermal infiltrates and epidermal microabscesses. In larger microabscesses neutrophils were predominant. These observations show that neutrophils and not only eosinophils recruit, accumulate, localize around and release their helminthotoxic granule proteins such as myeloperoxidase onto or closely around skin microfilariae of O. volvulus after topical DEC administration. The association between these processes and the damage of the microfilariae indicated that neutrophils together with eosinophils attack and damage microfilariae of O. volvulus after DEC treatment in the skin.
In the present review of twelve pieces produced by distinguished 20th century Latin American writers--Jorge Luis Borges from Argentina, Jorge Amado and João Ubaldo Ribeiro from Brazil, José Donoso from Chile, Gabriel García Márquez from Colombia, Alejo Carpentier from Cuba, Miguel Angel Asturias from Guatemala, Octavio Paz from Mexico, Mario Vargas Llosa from Perú, Horacio Quiroga and Mario Benedetti from Uruguay and Arturo Uslar-Pietri from Venezuela--paragraphs or parts of paragraphs in which parasitological or entomological situations of the most varied hues are referred to or described, have been extracted in a selective form. Sometimes in these descriptions appear, local or regional expressions, without ignoring colorful folklore representations. For a easier interpretation these or part of these paragraph sentences have been arranged by thematic similarities. In a varied and kaleidoscopic vision, it will be possible to find protozoiasis (malaria, Chagas disease, leishmaniasis, amebiasis), helminthiases (ascariasis, hydatidosis, trichinosis, schistosomiasis, cysticercosis, onchocerciasis), parasitoses produced by arthropods (pediculosis, scabies, tungiasis, myiasis), passing progressively to hemaphagous arthropods (mosquitoes, gnats, horse flies, bedbugs, ticks), venomous arthropods (Latrodectus spiders, scorpions, wasps, bees), mechanical vectors (flies and cockroaches), culminating with a conjunction of bucolic arthropods (butterflies, crickets, grasshoppers cicadas, ants, centipedes, beetles, glow worms, dragonflies).
Eberhard Mark L
Full Text Available Abstract Nowaday, zoonoses are an important cause of human parasitic diseases worldwide and a major threat to the socio-economic development, mainly in developing countries. Importantly, zoonotic helminths that affect human eyes (HIE may cause blindness with severe socio-economic consequences to human communities. These infections include nematodes, cestodes and trematodes, which may be transmitted by vectors (dirofilariasis, onchocerciasis, thelaziasis, food consumption (sparganosis, trichinellosis and those acquired indirectly from the environment (ascariasis, echinococcosis, fascioliasis. Adult and/or larval stages of HIE may localize into human ocular tissues externally (i.e., lachrymal glands, eyelids, conjunctival sacs or into the ocular globe (i.e., intravitreous retina, anterior and or posterior chamber causing symptoms due to the parasitic localization in the eyes or to the immune reaction they elicit in the host. Unfortunately, data on HIE are scant and mostly limited to case reports from different countries. The biology and epidemiology of the most frequently reported HIE are discussed as well as clinical description of the diseases, diagnostic considerations and video clips on their presentation and surgical treatment. Homines amplius oculis, quam auribus credunt Seneca Ep 6,5 Men believe their eyes more than their ears
Full Text Available Certain eyes are at a higher risk of complication during cataract surgery. Operations on such ‘high-risk’ eyes are also more likely to yield a poor visual outcome (defined as best corrected vision less than 6/60 after surgery.1Learning to recognise when eyes are at greater risk, and acting accordingly, will help you to avoid complications. Even so, before the operation takes place, it is good practice to explain to such patients that a poor outcome is a possibility. This makes these patients’ expectations more realistic and improves postoperative compliance and follow-up. In most cases, patients who are blind with complicated cataract will be happy with even a modest improvement of their vision.It is also important to have available all the equipment you may need to manage a possible complication, for example a vitrectomy machine in the case of capsular rupture and vitreous loss.Depending on where you are in the world, certain ‘high-risk’ eyes will be more common: for example, pseudoexfoliation in Somalia and India, onchocerciasis in Sudan, and angle-closure glaucoma in Asia. You will get to know your local problems as you perform more operations.
Hugh R Taylor
Full Text Available When looking ahead, it is really important to know where we have come from. This allows us to project identified trends and to reflect on the tremendous amount of change that can happen over a relatively short period.Reflect for a moment on the intensity of the debate regarding the use of intraocular lenses (IOLs in low-income settings in the 1990s. As they were still very expensive, some insisted that aphakic correction after surgery was the best approach for these countries. The subsequent availability of low-cost IOLs made the debate irrelevant. It dramatically changed our ability to provide modern IOL cataract surgery and control cataract blindness worldwide, and it laid the basis for VISION 2020. Other dramatic changes occurred with the introduction of ivermectin for onchocerciasis and azithromycin for trachoma, which gave us the ability to eliminate these two devastating and previously intractable causes of blindness. Our medical management of glaucoma or of age-related macular degeneration today is totally different from what it was 20 years ago, although there is still a long way to go. Our approach to refractive error has also altered dramatically, thanks to the recognition of its importance and the availability of high-quality, low-cost spectacles.So, given what we know about the past, what are the challenges we face in the future?
Kabatereine, Narcis B; Malecela, Mwele; Lado, Mounir; Zaramba, Sam; Amiel, Olga; Kolaczinski, Jan H
Combining the delivery of multiple health interventions has the potential to minimize costs and expand intervention coverage. Integration of mass drug administration is therefore being encouraged for delivery of preventive chemotherapy (PCT) to control onchocerciasis, lymphatic filariasis, schistosomiasis, soil-transmitted helminthiasis, and trachoma in sub-Saharan Africa, as there is considerable geographical overlap of these neglected tropical diseases (NTDs). With only a handful of countries having embarked on integrated NTD control, experience on how to develop and implement an efficient integrated programme is limited. Historically, national and global programmes were focused on the control of only one disease, usually through a comprehensive approach that involved several interventions including PCT. Overcoming the resulting disease-specific structures and thinking, and ensuring that the integrated programme is embedded within the existing health structures, pose considerable challenges to policy makers and implementers wishing to embark on integrated NTD control. By sharing experiences from Uganda, Tanzania, Southern Sudan, and Mozambique, this symposium article aims to outlines key challenges and solutions to assist countries in establishing efficient integrated NTD programmes.
Brooker, S; Kabatereine, N B; Gyapong, J O; Stothard, J R; Utzinger, J
There is growing interest and commitment to the control of schistosomiasis and other so-called neglected tropical diseases (NTDs). Resources for control are inevitably limited, necessitating assessment methods that can rapidly and accurately identify and map high-risk communities so that interventions can be targeted in a spatially-explicit and cost-effective manner. Here, we review progress made with (1) mapping schistosomiasis across Africa using available epidemiological data and, more recently, climate-based risk prediction; (2) the development and use of morbidity questionnaires for rapid identification of high-risk communities of urinary schistosomiasis; and (3) innovative sampling-based approaches for intestinal schistosomiasis, using the lot quality assurance sampling technique. Experiences are also presented for the rapid mapping of other NTDs, including onchocerciasis, loiasis and lymphatic filariasis. Future directions for an integrated rapid mapping approach targeting multiple NTDs simultaneously are outlined, including potential challenges in developing an integrated survey tool. The lessons from the mapping of human helminth infections may also be relevant for the rapid mapping of malaria as its control efforts are intensified.
Magalhães, Ricardo J Soares; Clements, Archie C A; Patil, Anand P; Gething, Peter W; Brooker, Simon
Funding agencies are dedicating substantial resources to tackle helminth infections. Reliable maps of the distribution of helminth infection can assist these efforts by targeting control resources to areas of greatest need. The ability to define the distribution of infection at regional, national and subnational levels has been enhanced greatly by the increased availability of good quality survey data and the use of model-based geostatistics (MBG), enabling spatial prediction in unsampled locations. A major advantage of MBG risk mapping approaches is that they provide a flexible statistical platform for handling and representing different sources of uncertainty, providing plausible and robust information on the spatial distribution of infections to inform the design and implementation of control programmes. Focussing on schistosomiasis and soil-transmitted helminthiasis, with additional examples for lymphatic filariasis and onchocerciasis, we review the progress made to date with the application of MBG tools in large-scale, real-world control programmes and propose a general framework for their application to inform integrative spatial planning of helminth disease control programmes.
Mohammed, Khalfan A.; Haji, Hamad J.; Gabrielli, Albis-Francesco; Mubila, Likezo; Biswas, Gautam; Chitsulo, Lester; Bradley, Mark H.; Engels, Dirk; Savioli, Lorenzo; Molyneux, David H.
Background Public health interventions based on distribution of anthelminthic drugs against lymphatic filariasis (LF), onchocerciasis, soil-transmitted helminthiasis (STH) and schistosomiasis have been implemented separately to date. A better use of available resources might be facilitated by a more coordinated approach to control such infections, including the possibility of co-administering the three recommended anthelminthic drugs through a single, large-scale intervention. Methodology/Principal Findings Ivermectin, albendazole and praziquantel were co-administered to 5,055 children and adults living in areas endemic for LF, STH and schistosomiasis in Zanzibar, United Republic of Tanzania, during a pilot intervention aimed at elucidating and quantifying possible side-effects. Subsequently, these drugs were co-administered to about 700,000 individuals during a countrywide intervention targeting a large part of the total population of Zanzibar. Passive and active surveillance measures carried out during both interventions showed that side-effects attributable to the three drugs given at the same time were mild and self-limiting events. Conclusions/Significance Our data suggest that co-administration of ivermectin, albendazole and praziquantel is safe in areas where lymphatic filariasis, soil-transmitted helminthiasis and schistosomiasis are co-endemic and where several rounds of treatment with one or two drugs have been implemented in the past. Passive surveillance measures, however, should be continued and detection, management and reporting of possible side-effects should be considered a key component of any health intervention administering drugs. PMID:18235853
Southgate, B A
Currently available methods for measuring the intensity of transmission in the lymphatic filariases are all to some extent unsatisfactory. Clinical methods for defining the presence of filarial disease are also less than perfect, and many infected persons remain free of symptoms and signs for very long periods. Incidence rates of microfilaraemia calculated from prevalence rate data are combined with 'entomological inoculation rates' obtained by direct observations of vector landing rates, infective larval rates and infective larval densities in field studies to determine efficiencies of transmission, and to relate transmission parameters to observed microfilarial and disease prevalence rates. Published studies from various endemic areas of the world which provide sufficient data have been analysed, using reversible catalytic models. In general, it seems that much less intense levels of transmission are needed in sub-Saharan Africa to produce given rates of microfilaraemia and disease than in Asia and Oceania, in the case of Wuchereria bancrofti infections; similarly, the genus Anopheles appears to produce infection and disease much more efficiently than the genera Culex and Aedes when transmitting W. bancrofti. The only example of Brugia malayi transmitted by Mansonia spp. analysed provided the highest level of transmission efficiency found. Tolerable levels of transmission analogous to those used in onchocerciasis cannot at present be defined for the lymphatic filariases; it seems that the intensity of transmission required to produce new cases of disease is probably below that required to produce new cases or episodes of readily detectable microfilaraemia.
Doran L Fink
Full Text Available Accurate diagnosis of Loa loa infection is essential to the success of mass drug administration efforts to eliminate onchocerciasis and lymphatic filariasis, due to the risk of fatal encephalopathic reactions to ivermectin occurring among highly microfilaremic Loa-infected individuals living in areas co-endemic for multiple filarial species.From a pool of over 1,800 L. loa microfilaria (mf expressed sequence tags, 18 candidate L. loa mf-specific PCR targets were identified. Real-time PCR (qPCR assays were developed for two targets (LLMF72 and LLMF269. The qPCR assays were highly specific for L. loa compared with related filariae and also highly sensitive, with detection limits of 0.1 pg genomic DNA, or 1% of DNA extracted from normal blood spiked with a single L. loa microfilaria. Using various DNA extraction methods with dried blood spots obtained from Cameroonian subjects with parasitologically proven loiasis, the LLMF72 qPCR assay successfully estimated mf burden in 65 of 68 samples (50-96,000 mf/mL by microscopy, including all 12 samples subjected to a simple 10-minute boiling extraction. Additionally, the assay detected low-level microfilaremia among 5 of 16 samples from patients thought to be amicrofilaremic by microscopy.This novel, rapid, highly sensitive and specific qPCR assay is an important step forward in the laboratory diagnosis of L. loa infection.
Churcher, Thomas S; Pion, Sébastien D S; Osei-Atweneboana, Mike Y; Prichard, Roger K; Awadzi, Kwablah; Boussinesq, Michel; Collins, Richard C; Whitworth, James A; Basáñez, María-Gloria
Identification of drug resistance before it becomes a public health concern requires a clear distinction between what constitutes a normal and a suboptimal treatment response. A novel method of analyzing drug efficacy studies in human helminthiases is proposed and used to investigate recent claims of atypical responses to ivermectin in the treatment of River Blindness. The variability in the rate at which Onchocerca volvulus microfilariae repopulate host's skin following ivermectin treatment is quantified using an individual-based onchocerciasis mathematical model. The model estimates a single skin repopulation rate for every host sampled, allowing reports of suboptimal responses to be statistically compared with responses from populations with no prior exposure to ivermectin. Statistically faster rates of skin repopulation were observed in 3 Ghanaian villages (treated 12-17 times), despite the wide variability in repopulation rates observed in ivermectin-naïve populations. Another village previously thought to have high rates of skin repopulation was shown to be indistinguishable from the normal treatment response. The model is used to generate testable hypotheses to identify whether atypical rates of skin repopulation by microfilariae could result from low treatment coverage alone or provide evidence of decreased ivermectin efficacy. Further work linking phenotypic poor responses to treatment with parasite molecular genetics markers will be required to confirm drug resistance. Limitations of the skin-snipping method for estimating parasite load indicates that changes in the distribution of microfilarial repopulation rates, rather than their absolute values, maybe a more sensitive indicator of emerging ivermectin resistance.
Chosidow, A; Gendrel, D
Ivermectin is an antiparasitic drug, a derivate of avermectins, and a product of fermentation of an actinomycete, Streptomyces avermitilis. Its structure associates two avermectins. Ivermectin acts on the chloride-dependent channels of both glutamate and γ-aminobutyric acid, interrupting neurotransmission in invertebrates. In humans, several mechanisms of brain protection exist, including P-glycoprotein, present on the apical face of endothelial cells of the blood-brain barrier and coded by the MDR1 gene. Ivermectin is presently used in mass treatment of onchocerciasis, other filariasis, some intestinal nematode infections, but also in scabies, and more rarely in resistant head lice. The side effects described are related to the release of antigen and cause an inflammatory reaction. Studies conducted in children or infants have shown good tolerance of ivermectin. However, its use in infants who weigh less than 15kg is a problem because of the absence of marketing authorization for this age group. However, the risk of excessive and uncontrolled use in head lice requires close surveillance.
Wilson Michael D
Full Text Available Abstract Background The control of onchocerciasis in the African region is currently based mainly on the mass drug administration of ivermectin. Whilst this has been found to limit morbidity, it does not stop transmission. In the absence of a macrofilaricide, there is a need for an integrated approach for disease management, which includes vector control. Vector control using chemical insecticides is expensive to apply, and therefore the use of other measures such as biological control agents is needed. Immature stages of Simulium squamosum, reared in the laboratory from egg masses collected from the field at Boti Falls and Huhunya (River Pawnpawn in Ghana, were observed to be attacked and fed upon by larvae of the chironomid Cardiocladius oliffi Freeman, 1956 (Diptera: Chironomidae. Methods Cardiocladius oliffi was successfully reared in the rearing system developed for S. damnosum s.l. and evaluated for its importance as a biological control agent in the laboratory. Results Even at a ratio of one C. oliffi to five S. squamosum, they caused a significant decrease in the number of adult S. squamosum emerging from the systems (treatments. Predation was confirmed by the amplification of Simulium DNA from C. oliffi observed to have fed on S. squamosum pupae. The study also established that the chironomid flies could successfully complete their development on a fish food diet only. Conclusion Cardiocladius oliffi has been demonstrated as potential biological control agent against S. squamosum.
Full Text Available In order to clarify the genetic differences between Onchocerca dewittei japonica, the causative agent of zoonotic onchocerciasis in Japan and a related undescribed Onchocerca sp., both parasitizing wild boar (Sus scrofa of which the infective larval stages are indistinguishable from each other, we compared the sequences of the mitochondrial cytochrome c oxidase subunit 1 (CO1 gene region from four infective larvae (recovered from experimentally infected black flies, one microfilaria, and one adult of O. dewittei japonica, and from one infective larva (recovered from an experimentally infected black fly, one microfilaria, and a pool of several microfilariae of O. sp. The length of the CO1 gene region was 649 bp for all samples but there was a difference of 8.8 to 9.4% in the sequences between the two species although there were intraspecific variations of 0 to 0.5%. The CO1 sequences of O. sp. did not correspond to any of those deposited in the databases. Our study provides evidence that O. dewittei japonica and O. sp. are genetically different from each other.
Reid, G D
Cibarial armature morphology in adult female blackflies (Diptera: Simuliidae) is described using scanning electron microscopy. Three distinct types of armature are recognized, comprising those with teeth, e.g. Simulium ochraceum, S. ornatum, S. veracruzanum and S. vorax, those with spicules, e.g. Austrosimulium bancrofti, S. damnosum, S. exiguum, S. metallicum and S. neavei; and those lacking these projections, e.g. Prosimulium rufipes and S. lineatum. Whereas the armature is poorly developed in vectors of human onchocerciasis such as S. damnosum, S. exiguum, S. metallicum and S. neavei, the well-developed armature in S. ochraceum, S. veracruzanum and S. vorax does not prevent these species becoming infected with Onchocerca spp. (Nematoda: Onchocercidae). Hence the armature is not primarily a mechanism to counteract microfilaria superinfection. Since cibarial armatures are more developed in the haematophagous females than in the males of certain Families of flies, e.g. Ceratopogonidae, Culicidae, Phlebotominae and Simuliidae in the sub-order Nematocera, evidently the armature has evolved in response to the blood-feeding habit. As the suction of imbibed blood by the cibarial pump may require a valve mechanism to prevent back-flow, it is suggested that the armature is primarily for this purpose. Secondarily, the cibarial armature presents a damaging barrier against ingested microfilariae.
Beaumier, Coreen M; Gillespie, Portia M; Hotez, Peter J; Bottazzi, Maria Elena
Neglected tropical diseases (NTDs) are a significant source of morbidity and socioeconomic burden among the world's poor. Virtually all of the 2.4 billion people who live on less than $2 per d, more than a third of the world's population, are at risk for these debilitating NTDs. Although chemotherapeutic measures exist for many of these pathogens, they are not sustainable countermeasures on their own because of rates of reinfection, risk of drug resistance, and inconsistent maintenance of drug treatment programs. Preventative and therapeutic NTD vaccines are needed as long-term solutions. Because there is no market in the for-profit sector of vaccine development for these pathogens, much of the effort to develop vaccines is driven by nonprofit entities, mostly through product development partnerships. This review describes the progress of vaccines under development for many of the NTDs, with a specific focus on those about to enter or that are currently in human clinical trials. Specifically, we report on the progress on dengue, hookworm, leishmaniasis, schistosomiasis, Chagas disease, and onchocerciasis vaccines. These products will be some of the first with specific objectives to aid the world's poorest populations. Copyright © 2013 Mosby, Inc. All rights reserved.
Narcis B Kabatereine
Full Text Available Combining the delivery of multiple health interventions has the potential to minimize costs and expand intervention coverage. Integration of mass drug administration is therefore being encouraged for delivery of preventive chemotherapy (PCT to control onchocerciasis, lymphatic filariasis, schistosomiasis, soil-transmitted helminthiasis, and trachoma in sub-Saharan Africa, as there is considerable geographical overlap of these neglected tropical diseases (NTDs. With only a handful of countries having embarked on integrated NTD control, experience on how to develop and implement an efficient integrated programme is limited. Historically, national and global programmes were focused on the control of only one disease, usually through a comprehensive approach that involved several interventions including PCT. Overcoming the resulting disease-specific structures and thinking, and ensuring that the integrated programme is embedded within the existing health structures, pose considerable challenges to policy makers and implementers wishing to embark on integrated NTD control. By sharing experiences from Uganda, Tanzania, Southern Sudan, and Mozambique, this symposium article aims to outlines key challenges and solutions to assist countries in establishing efficient integrated NTD programmes.
Park, S; Albert, D M; Bolognia, J L
Disorders of pigmentation can result from either an abnormal number of melanocytes, as in nevus of Ota and vitiligo, or an abnormal amount of melanin production, as in albinism. Melanin-producing cells are found in the skin, mucous membranes, uveal tract, and retinal pigment epithelium of the eye and the stria vascularis of the inner ear. Thus, many of the hereditary or congenital pigmentary disorders of the skin are associated with similar pigmentary abnormalities in the eye, such as iris heterochromia or changes in pigmentation of the fundus; however, more commonly, the associated eye finding is a defect in ocular motility, i.e., strabismus and nystagmus, suggesting a concomitant defect in neurologic development. In albinos, the observed neurologic abnormality in the visual pathway and foveal hypoplasia are hypothesized to be related directly to the lack of melanin in the pigment epithelium during development. In acquired disorders of pigmentation, in particular, vitiligo, Vogt-Koyanagi-Harada syndrome, and onchocerciasis, there is a frequent association with uveitis, suggesting an inflammatory cause for the cutaneous pigmentary changes.
Full Text Available Reliable information is required for the planning and management of eye care services. While classical research methods provide reliable estimates, they are prohibitively expensive and resource intensive. Rapid assessment (RA methods are indispensable tools in situations where data are needed quickly and where time- or cost-related factors prohibit the use of classical epidemiological surveys. These methods have been developed and field tested, and can be applied across almost the entire gamut of health care. The 1990s witnessed the emergence of RA methods in eye care for cataract, onchocerciasis, and trachoma and, more recently, the main causes of avoidable blindness and visual impairment. The important features of RA methods include the use of local resources, simplified sampling methodology, and a simple examination protocol/data collection method that can be performed by locally available personnel. The analysis is quick and easy to interpret. The entire process is inexpensive, so the survey may be repeated once every 5-10 years to assess the changing trends in disease burden. RA survey methods are typically linked with an intervention. This article provides an overview of the RA methods commonly used in eye care, and emphasizes the selection of appropriate methods based on the local need and context.
Infecto-contagious diseases in the twenty-first century with respect to precedent will see themselves deprived of smallpox, dracunculiasis and very probably of paralyzing poliomyelitis. Vaccination-preventable diseases, such as measles, whooping cough, diphtheria, tetanus, rabies, some forms of meningitis, yellow fever and episodes of disseminated tuberculosis will greatly diminish in their rates of morbi-lethality; the elimination of some, and the eradication of measles, are expected. Other diseases such as diarrhea (including cholera), geo-helminthiasis, some severe respiratory tract infections and the majority of vector-transmitted infectious diseases will decrease due to improvements in potable water services, drainage, sanitary food control, living quarters, and individual and community anti-vector action. Leprosy, onchocerciasis and several parasitoses will be controlled by the available antimicrobial drugs. Infectious diseases will continue to be an important health problem due to: Reduction in the immunocompetence resulting from the aging of the population, chemotherapies necessary for neoplasms, and autoimmune pathology and the survival of persons with primary immunodeficiencies; lifestyles prone to infectious pathology, such as mega-city urbanization, children in day care centers, industrialized foods, intravenous drug addiction, sexual liberation, global commerce, and tourism; antibiotic-multiresistant microbial flora; environmental disturbances as a result of global warming, deforestation, the settling of virgin areas, dams, the large-scale use of pesticides, fertilizers and antimicrobials, and natural/social disasters generators of poverty, violence and deprivation will result in emergence or re-emergence of infectious diseases already controlled in the past.
Adeleke, Monsuru Adebayo; Sam-Wobo, Sammy Olufemi; Akinwale, Olaoluwa Pheabian; Olatunde, Ganiyu Olatunji; Mafiana, Chiedu Felix
The biting preference of Simulium vectors has been known to influence the distribution of Onchocerca nodules and microfilariae in human body. There is, however, variation in biting pattern of Simulium flies in different geographical locations. This study investigates the biting pattern on human parts by Simulium vectors along Osun river system where Simulium soubrense Beffa form has been implicated as the dominant vector and its possible implication on the distribution of Onchocerca nodules on human body along the river. Flies were collected by consented fly capturers on exposed human parts namely head/neck region, arms, upper limb and lower limb in Osun Eleja and Osun Budepo along Osun river in the wet season (August-September) and the dry season (November-December) in 2008. The residents of the communities were also screened for palpable Onchocerca nodules. The results showed that number of flies collected below the ankle region was significantly higher than the number collected on other exposed parts (p parts coupled with the presence of nodules at the head and upper trunk regions showed that Simulium vectors could obtain microfilariae from any part of the body, thus increasing the risk of onchocerciasis transmission.
Full Text Available Background & objectives: Onchocerciasis is endemic in some parts of Akwa Ibom State, Nigeria. This study describes the entomological parameters of transmission in three rural communities of Akwa Ibom State, prior to ivermectin intervention in 2004. Methods: Blackflies were caught using human bait and 90% of the flies were dissected for parity. All parous flies were further dissected for the presence of filaria larvae. Monthly and annual biting rate, and transmission potential were calculated using standard methods.Results: A total of 4296 adult Simulium damnosum were caught on human bait, 4119 were dissected of which 208 (5.1% were infected with Onchocerca volvulus larvae. Transmission parameters varied significantly (p < 0.05 in the three villages. Annual biting rates, ranged from 9490 to 11,218 bites per person per year. The annual transmission potential ranged from 131 to 189 infective larvae per person per year, monthly biting rate and monthly transmission potential varied significantly (p < 0.05 in the three villages. Transmission was highly seasonal occurring during the peak of rainy season from August to October. There was no transmission during the dry periods — November to March, and the early rainy periods — April to May. The diurnal biting activity of the fly exhibited a bimodal pattern with a morning peak (0900–1000 hrs and a more marked evening peak (1600–1700 hrs. Interpretation & conclusion: The results indicate that there is a temporal and spatial variation in the transmission dynamics of S. damnosum in the study area.
Krueger, A; Fischer, P; Morales-Hojas, R
Filarial parasites of the genus Onchocerca are found in a broad spectrum of ungulate hosts. One species, O. volvulus, is a human parasite that can cause severe disease (onchocerciasis or 'river blindness'). The phylogenetic relationships and the bionomics of many of the nearly 30 known species remain dubious. Here, the phylogeny of 11 species representing most major lineages of the genus is investigated by analysing DNA sequences from three mitochondrial genes (ND5, 12S and 16S rRNA) and portions of the intergenic spacer of the nuclear 5s rRNA. Special emphasis is given to a clade containing a yet unassigned specimen from Uganda (O. sp. 'Siisa'), which appears to be intermediate between O. volvulus and O. ochengi. While the latter can be differentiated by the O-150 tandem repeat commonly used for molecular diagnostics, O. volvulus and O. sp.'Siisa' cannot be differentiated by this marker. In addition, a worm specimen from an African bushbuck appears to be closely related to the bovine O. dukei and represents the basal taxon of the human/bovine clade. At the base of the genus, our data suggest O. flexuosa (red deer), O. ramachandrini (warthog) and O. armillata (cow) to be the representatives of ancient lineages. The results provide better insight into the evolution and zoogeography of Onchocerca. They also have epidemiological and taxonomic implications by providing a framework for more accurate molecular diagnosis of filarial larvae in vectors.
Full Text Available We describe Onchocerca dewittei japonica n. subsp. from the Japanese wild boar, Sus scrofa leucomystax, in Oita, Kyushu Island, where all seven animals examined were found to be infected. This study began with efforts to identify the causative species in a recent case of zoonotic onchocerciasis. Compared with Onchocerca dewittei dewittei from Sus scrofa jubatus in Malaysia, which was reexamined here, our new subspecies has much greater space between the ridges on the females. In addition, its microfilariae (from uteri are shorter (192-210 μm compared with 228-247 μm, and only the posterior third of the microfilarial body is coiled, instead of the entire body. The Onchocerca species parasitic in suids (these two subspecies and O. ramachandrini from the warthog in the Ethiopian region form a group sharing several characters. Among the most unusual characters are the body swellings (a specialized apparatus for mating, known in only a few other genera. In addition, longitudinal cuticular crests were found on males of both subspecies from wild boar and on females of O. ramachandrini.
Borchert, Nadine; Becker-Pauly, Christoph; Wagner, Antje; Fischer, Peter; Stöcker, Walter; Brattig, Norbert W
The tissue-invasive nematode Onchocerca volvulus causes skin and eye pathology in human onchocerciasis. While the adult females reside sessile in subcutaneous nodules, the microfilariae are abundantly released from the nodules, males and juvenile worms migrate through the host tissue. Matrix-degrading metallo- and serine proteinases have been detected in excretory-secretory worm products that may be essential for migration of the mobile stages. In this study, a 1713bp long cDNA encoding for a putative proteinase of O. volvulus has been isolated. The predicted protein sequence includes a signal peptide indicating secretion to the extracellular space, a propeptide, an astacin-like protease domain, an EGF-like and a CUB-domain, thereby identifying the protein as a member of the astacin family of zinc endopeptidases. Onchoastacin, Ov-AST-1, is most closely related to a subfamily comprising nematode astacins including Caenorhabditis and Ancylostoma. Ov-AST-1 was expressed as a recombinant protein in baculovirus-infected insect cells and exhibited enzymatic activity. The exposure of onchoastacin to the host immune system is indicated by demonstration of IgG reacting with the recombinant Ov-AST-1 and with two peptides of the protein. Since a homologous metalloproteinase is part of a promising hookworm vaccine, Ov-AST-1 may be a candidate for intervention strategies in filarial infections.
Monnerat, Rose; Pereira, Eleny; Teles, Beatriz; Martins, Erica; Praça, Lilian; Queiroz, Paulo; Soberon, Mario; Bravo, Alejandra; Ramos, Felipe; Soares, Carlos Marcelo
Species of Simulium spread diseases in humans and animals such as onchocerciasis and mansonelosis, causing health problems and economic loses. One alternative for controlling these insects is the use of Bacillus thuringiensis serovar israelensis (Bti). This bacterium produces different dipteran-active Cry and Cyt toxins and has been widely used in blackfly biological control programs worldwide. Studies on other insect targets have revealed the role of individual Cry and Cyt proteins in toxicity and demonstrated a synergistic effect among them. However, the insecticidal activity and interactions of these proteins against Simulium larvae have not been reported. In this study we demonstrate that Cry4Ba is the most effective toxin followed by Cry4Aa and Cry11Aa. Cry10Aa and Cyt1Aa were not toxic when administered alone but both were able to synergise the activity of Cry4B and Cry11Aa toxins. Cyt1Aa is also able to synergise with Cry4Aa. The mixture of all toxin-producing strains showed the greatest level of synergism, but still lower than the Bti parental strain.
Bockarie, Moses J; Kelly-Hope, Louise A; Rebollo, Maria; Molyneux, David H
Global efforts to address neglected tropical diseases (NTDs) were stimulated in January 2012 by the London declaration at which 22 partners, including the Bill & Melinda Gates Foundation, World Bank, World Health Organization (WHO) and major pharmaceutical companies committed to sustaining and expanding NTD programmes to eliminate or eradicate 11 NTDs by 2020 to achieve the goals outlined in the recently published WHO road map. Here, we present the current context of preventive chemotherapy for some NTDs, and discuss the problems faced by programmes as they consider the 'endgame', such as difficulties of access to populations in post-conflict settings, limited human and financial resources, and the need to expand access to clean water and improved sanitation for schistosomiasis and soil-transmitted helminthiasis. In the case of onchocerciasis and lymphatic filariasis, ivermectin treatment carries a significant risk owing to serious adverse effects in some patients co-infected with the tropical eye worm Loa loa filariasis. We discuss the challenges of managing complex partnerships, and maintain advocacy messages for the continued support for elimination of these preventable diseases.
Infante-Rodríguez, Dennis A; Novelo-Gutiérrez, Rodolfo; Mercado, Gabriel; Williams, Trevor
Spinosad is a naturally derived insecticide that has shown potential as a mosquito larvicide. To determine the activity of spinosad against blackflies, late-instar larvae from a community comprising Simulium triittatum (63.6%) and seven other species, including three known vectors of onchocerciasis in Mexico (S. metallicum, S. ochraceum, and S. callidum), were subjected to concentration-mortality laboratory bioassays following World Health Organization guidelines. Cephalic capsule measurements confirmed the relatively homogeneous distribution of experimental larvae. The 50% lethal concentration of spinosad was estimated at 1.48 ppm spinosad (95% confidence interval: 1.07-2.33) for a 10-min exposure period, whereas larvae treated with 0.05 ppm of the organophosphate temephos experienced 61% mortality. Immature aquatic insects were identified to genus and tested for their susceptibility to spinosad in the laboratory. After exposure to 12 ppm spinosad for 10 min, ephemeropterans, odonates, trichopterans, and hemipterans did not experience significantly increased mortality over that of untreated controls, whereas a significant increase in mortality was observed in spinosad-treated Plecoptera (P < 0.001). Tilapia and trout fry exposed to 12 ppm spinosad for 10 min did not experience increased mortality at 24-h postexposure over that of the controls. We conclude that spinosad is less toxic than temephos to these blackfly species, but is likely to have a low impact on nontarget members of the aquatic community.
Hofstraat, Karlijn; van Brakel, Wim H
People affected by neglected tropical diseases (NTDs) are frequently the target of social stigmatization. To date not much attention has been given to stigma in relation to NTDs. The objective of this review is to identify the extent of social stigma and the similarities and differences in the causes, manifestations, impact of stigma and interventions used between the NTDs. A systematic review was conducted in Pubmed, ScienceDirect, PsycINFO and Web of Knowledge. The search encompassed 17 NTDs, including podoconiosis, but not leprosy as this NTD has recently been reviewed. However, leprosy was included in the discussion. The 52 selected articles provided evidence on stigma related to lymphatic filariasis (LF), podoconiosis, Buruli ulcer, onchocerciasis, schistosomiasis, leishmaniasis, Chagas disease, trachoma, soil-transmitted helminthiasis (STH) and human African trypanosomiasis. The similarities predominated in stigma related to the various NTDs; only minimal differences in stigma reasons and measures were found. These similarities suggest that joint approaches to reduce stigmatization may be feasible. Lessons from leprosy and other stigmatized health conditions can be used to plan such joint approaches. Further research will be necessary to study the efficacy of joint interventions and to investigate stigma related to NTDs for which no evidence is available yet. © The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: firstname.lastname@example.org.
Sam-Wobo, Sammy O; Adeleke, Monsuru A; Mafiana, Chiedu F; Surakat, Olabanji H
The root and leaf extracts of four plants, Occimum gratissimum, Azadirachta indica, Pterocarpus santalinoides, and Pistia hyptis, were studied for repellent activities against the adults of Simulium damnosum sensu lato. The leaves and roots were extracted with 95% ethanol and the stocks were diluted with paraffin. The repellent activities of the extracts were investigated using human baits along the banks of River Oyan and River Ogun in southwestern Nigeria. The results showed that the root extract of O. grattissium and leaf extract of P. hyptis had highest repellent potentials with 78% and 78.1% protection against S. damnosum sensu lato, respectively, whereas the root and leaf of P. santalinoides recorded the least. Although there were significant differences in the percentage of protection of the extracts of the plants (p 0.05). The study concludes that there exist some repellent efficacies in the extracts of the plants, most importantly O. grattissimum and P. hyptis. The plant extracts can further be developed in the prevention of man-vector contact in onchocerciasis endemic communities.
Peter J Hotez
Full Text Available The neglected tropical diseases (NTDs represent some of the most common infections of the poorest people living in the Latin American and Caribbean region (LAC. Because they primarily afflict the disenfranchised poor as well as selected indigenous populations and people of African descent, the NTDs in LAC are largely forgotten diseases even though their collective disease burden may exceed better known conditions such as of HIV/AIDS, tuberculosis, or malaria. Based on their prevalence and healthy life years lost from disability, hookworm infection, other soil-transmitted helminth infections, and Chagas disease are the most important NTDs in LAC, followed by dengue, schistosomiasis, leishmaniasis, trachoma, leprosy, and lymphatic filariasis. On the other hand, for some important NTDs, such as leptospirosis and cysticercosis, complete disease burden estimates are not available. The NTDs in LAC geographically concentrate in 11 different sub-regions, each with a distinctive human and environmental ecology. In the coming years, schistosomiasis could be eliminated in the Caribbean and transmission of lymphatic filariasis and onchocerciasis could be eliminated in Latin America. However, the highest disease burden NTDs, such as Chagas disease, soil-transmitted helminth infections, and hookworm and schistosomiasis co-infections, may first require scale-up of existing resources or the development of new control tools in order to achieve control or elimination. Ultimately, the roadmap for the control and elimination of the more widespread NTDs will require an inter-sectoral approach that bridges public health, social services, and environmental interventions.
Aloo, P A
The majority of the numerous fish parasites are harmless to man and many domestic animals because when eaten with their fish hosts, they are digested. However, some of the fish parasites with larval stages in freshwater or marine teleosts have zoonotic potential if eaten raw or partially cooked. These are usually parasites, which have a piscivorous mammalian carnivore as their normal final host and are able to infect man because of the low host specificity of the adult stage. The major groups of fish parasite that are known as potentially dangerous pathogens of man belong to the helminth groups cestoda, trematoda, nematoda and rarely acanthocephala. However, bacterial and viral disease of man transmitted through fish are not uncommon. Toxic substances, metals and insecticides used to control human diseases in aquatic environments may accumulate in fish in po1lluted waters at such levels as to constitute a health risk to the consumer. Other health problems associated with fish arise from its perishable nature for example, in adequate handling, processing and storage, which may lead to the accumulation of microbes enhancing the risk of food poisoning. The aquatic environment in Africa constitutes a breeding habitat to several vectors of human diseases such as mosquitoes, snails and black flies. This paper reviews the role played by fish in transmitting diseases to humans as well as the importance of the aquatic environments in the transmission of human diseases such as Malaria, Schistosomiasis and onchocerciasis.
Miller, M J
Levamisole is a drug of choice for treatment of ascariasis. With recommended dosages, it is virtually free of side effects. Single doses of 50 to 150mg will eliminate all parasites in 90 to 100% of ascariasis patients irrespective of worm burden. Activity against hookworms has been demonstrated for levamisole but the most effective treatment regimen has not been determined. Further drug trials are needed for better assessment of efficacy. Levamisole has little or no curative action on infections with whipworms and pinworms. It may have some activity against strongyloides but confirmatory studies are needed. It has been shown that levamisole has significant activity against microfilariae of Wuchereria bancrofti and Brugia malayi. It is not, however, as effective as diethylcarbamazine ('Hetrazan'), and side reactions are greater. In tolerated doses, levamisole does not have significant action on adult forms or microfilariae of Onchoceea volvulus. The drug applied topically, however, may find a place in treatment of ocular onchocerciasis. Limited trials with levamisole for toxoplasmosis and chronic cutaneous leishmaniasis have given promising results, and further studies are indicated.
Rodríguez-Pérez, Mario A; Unnasch, Thomas R; Domínguez-Vázquez, Alfredo; Morales-Castro, Alba L; Peña-Flores, Graciela P; Orozco-Algarra, María E; Arredondo-Jiménez, Juan I; Richards, Frank; Vásquez-Rodríguez, Miguel A; Rendón, Vidal García
All endemic communities of the Oaxaca focus of onchocerciasis in southern Mexico have been treated annually or semi-annually with ivermectin since 1994. In-depth epidemiologic assessments were performed in communities during 2007 and 2008. None of the 52,632 Simulium ochraceum s.l. collected in four sentinel communities was found to contain parasite DNA when tested by polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA), resulting in an upper bound of the infection rate in the vectors of 0.07/2,000. The prevalence of microfilariae (mf) in the cornea and/or anterior chamber of the eye was also zero (0 of 1,039 residents examined; 95%-UL = 0.35%). Similarly, all 1,164 individuals examined by skin biopsy were mf negative (95%-UL = 0.31%), and sera collected from 3,569 children from 25 communities did not harbor Ov16 IgG4-antibodies (95%-UL = 0.09%). These meet the criteria for absence of morbidity and parasite transmission in the Oaxaca focus. As a result mass treatments with ivermectin were halted in 2009.
Full Text Available Helminth infections are responsible for a considerable public health burden, yet the current drug armamentarium is small. Given the high cost of drug discovery and development, the high failure rates and the long duration to develop novel treatments, drug repurposing circumvents these obstacles by finding new uses for compounds other than those they were initially intended to treat. In the present review, we summarize in vivo and clinical trial findings testing clinical candidates and marketed drugs against schistosomes, food-borne trematodes, soil-transmitted helminths, Strongyloides stercoralis, the major human filariases lymphatic filariasis and onchocerciasis, taeniasis, neurocysticercosis and echinococcosis. While expanding the applications of broad-spectrum or veterinary anthelmintics continues to fuel alternative treatment options, antimalarials, antibiotics, antiprotozoals and anticancer agents appear to be producing fruitful results as well. The trematodes and nematodes continue to be most investigated, while cestodal drug discovery will need to be accelerated. The most clinically advanced drug candidates include the artemisinins and mefloquine against schistosomiasis, tribendimidine against liver flukes, oxantel pamoate against trichuriasis, and doxycycline against filariasis. Preclinical studies indicate a handful of promising future candidates, and are beginning to elucidate the broad-spectrum activity of some currently used anthelmintics. Challenges and opportunities are further discussed.
Tamarozzi, F; Wright, H L; Johnston, K L; Edwards, S W; Turner, J D; Taylor, M J
The host inflammatory response to the Onchocerca volvulus endosymbiont, Wolbachia, is a major contributing factor in the development of chronic pathology in humans (onchocerciasis/river blindness). Recently, the toll-like pattern recognition receptor motif of the major inflammatory ligands of filarial Wolbachia, membrane-associated diacylated lipoproteins, was functionally defined in murine models of pathology, including mediation of neutrophil recruitment to the cornea. However, the extent to which human neutrophils can be activated in response to this Wolbachia pattern recognition motif is not known. Therefore, the responses of purified peripheral blood human neutrophils to a synthetic N-terminal diacylated lipopeptide (WoLP) of filarial Wolbachia peptidoglycan-associated lipoprotein (PAL) were characterized. WoLP exposure led to a dose-dependent activation of healthy, human neutrophils that included gross morphological alterations and modulation of surface expressed integrins involved in tethering, rolling and extravasation. WoLP exposure induced chemotaxis but not chemokinesis of neutrophils, and secretion of the major neutrophil chemokine, interleukin 8. WoLP also induced and primed the respiratory burst, and enhanced neutrophil survival by delay of apoptosis. These results indicate that the major inflammatory motif of filarial Wolbachia lipoproteins directly activates human neutrophils in vitro and promotes a molecular pathway by which human neutrophils are recruited to sites of Onchocerca parasitism.
Carp, R I; Meeker, H C; Kozlowski, I; Sersen, E A
As we enter the post-genomic era, there is an increasing need for accurate methods of identifying host and pathogen factors that contribute to bacterial, viral and fungal disease. In addition, there is a requirement for fast and precise techniques to evaluate potential therapies for the prevention of infectious diseases. The development of useful and cost-effective model systems will be crucial in advancing our knowledge of all aspects of microbial pathogenesis. In this series, we will learn of animal models used to investigate diseases caused by a wide variety of pathogens, including HIV, Vibrio cholerae and Pseudomonas aeruginosa. A description of a model system specifically designed to study intracellular pathogens will be presented, as will a variety of the techniques currently used to exploit other useful models of infection. Additionally, a description of the mathematical models used to analyse the population biology of human onchocerciasis will be discussed. The series begins with an intriguing look at the possible connections between an endogenous retrovirus, the infectious agent of scrapie and accelerated senescence in a mouse model of early aging.
Ault, Steven Kenyon; Catalá Pascual, Laura; Grados-Zavala, Maria Elena; Gonzálvez García, Guillermo; Castellanos, Luis Gerardo
Neglected infectious diseases (NID) affect mainly isolated populations living in isolation and in poor socioeconomic conditions. These diseases, by their chronic and silent nature, often affect communities with a weak political voice. This translates into very little attention or political priority; which is reflected in minimal and insufficient preventive measures, monitoring and control. However, there is evidence this situation is changing favorably in some countries of the Americas. In recent years, several resolutions (official agreement of the member countries of the Pan American Health Organization / World Health Organization-PAHO / WHO), regional and global agreements on public health; with a greater commitment from the pharmaceutical industry, and other donors and international partners in combination with the development and use of integrated action plans have allowed countries to intensify public interventions to control these diseases and thus achieve target elimination of NID. Onchocerciasis, lymphatic filariasis, Chagas disease, leprosy and trachoma blindness, among others, have been eliminated in several countries and endemic areas, regardless of the level of development of the country or geographical area where they are located. The political decision reflected in adequate financial resources in the next decade will be crucial to achieving the goals of elimination of NID (regional and national).
Ismail, M M; Jayakody, R L; Weil, G J; Nirmalan, N; Jayasinghe, K S; Abeyewickrema, W; Rezvi Sheriff, M H; Rajaratnam, H N; Amarasekera, N; de Silva, D C; Michalski, M L; Dissanaike, A S
In a 'blind' trial on 50 male asymptomatic microfilaraemic subjects with Wuchereria bancrofti infection, the safety, tolerability and filaricidal efficacy of a single dose of albendazole (alb) 600 mg alone or in combination with ivermectin (iver) 400 micrograms/kg or diethylcarbamazine citrate (DEC) 6 mg/kg was compared with a single dose of the combination DEC 6 mg/kg and iver 400 micrograms/kg over a period of 15 months after treatment. All but one subject, with 67 microfilariae (mf)/mL, had pre-treatment counts > 100 mf/mL. All 4 treatments significantly reduced mf counts, but alb/iver was the most effective regimen for clearing mf from night blood: 9 of 13 subjects (69%) were amicrofilaraemic by membrane filtration 15 months after treatment compared to one of 12 (8%), 3 of 11 (27%), and 3 of 10 (30%) in the groups treated with alb, alb/DEC, and DEC/iver, respectively. Filarial antigen tests suggested that all 4 treatments had significant activity against adult W. bancrofti; alb/DEC had the greatest activity according to this test, with antigen levels decreasing by 77% 15 months after therapy. All 4 regimens were well tolerated and clinically safe, although mild, self-limited systemic reactions were observed in all treatment groups. These results suggest that alb/iver is a safe and effective single dose regimen for suppression of microfilaraemia in bancroftian filariasis that could be considered for control programmes. Additional benefits of this combination are its potent, broad spectrum activity against intestinal helminths and potential relative safety in areas of Africa where DEC cannot be used for filariasis control because of co-endemicity with onchocerciasis or loiasis.
Two-year follow-up of the microfilaraemia of asymptomatic brugian filariasis, after treatment with two, annual, single doses of ivermectin, diethylcarbamazine and albendazole, in various combinations.
Shenoy, R K; John, A; Babu, B S; Suma, T K; Kumaraswami, V
Repeated, single, oral doses of combinations of ivermectin, diethylcarbamazine (DEC) or albendazole are recognized as important tools for parasite control in lymphatic filariasis. In order to assess the effects of re-treatment using these combinations in Brugia malayi infections, 40 asymptomatic microfilaraemics were re-treated at the end of the first year, with an additional, single, dose of the combination they had previously received. They were then followed-up for another year. The subjects, of both sexes and aged 14-70 years, each received a two-drug combination: ivermectin (200 micrograms/kg) with DEC (6 mg/kg); ivermectin (200 micrograms/kg) with albendazole (400 mg); or DEC (6 mg/kg) with albendazole (400 mg). The kinetics of microfilarial clearance were similar to that seen during the first treatment, the members of the two groups given DEC having less intense microfilaraemias, 1 year after the re-treatment, than those given ivermectin with albendazole (P comparison). At this time, the two DEC groups also had a higher proportion of amicrofilaraemic individuals (22 of 26) than the ivermectin + albendazole group (three of nine). There were fewer adverse reactions in all the groups after re-treatment than seen after the first treatment. In countries such as India, where there is no co-endemicity of onchocerciasis or loiasis, the options for control programmes in areas where brugian filariasis is endemic are DEC alone or DEC in combination with ivermectin or albendazole. Where there is no access to ivermectin, transmission control must be based on DEC alone or in combination with albendazole.
Stephen R Doyle
Full Text Available Treatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug administration is likely to exert selection pressure on parasites, and phenotypic and genetic changes in several Onchocerca volvulus populations from Cameroon and Ghana-exposed to more than a decade of regular ivermectin treatment-have raised concern that sub-optimal responses to ivermectin's anti-fecundity effect are becoming more frequent and may spread.Pooled next generation sequencing (Pool-seq was used to characterise genetic diversity within and between 108 adult female worms differing in ivermectin treatment history and response. Genome-wide analyses revealed genetic variation that significantly differentiated good responder (GR and sub-optimal responder (SOR parasites. These variants were not randomly distributed but clustered in ~31 quantitative trait loci (QTLs, with little overlap in putative QTL position and gene content between the two countries. Published candidate ivermectin SOR genes were largely absent in these regions; QTLs differentiating GR and SOR worms were enriched for genes in molecular pathways associated with neurotransmission, development, and stress responses. Finally, single worm genotyping demonstrated that geographic isolation and genetic change over time (in the presence of drug exposure had a significantly greater role in shaping genetic diversity than the evolution of SOR.This study is one of the first genome-wide association analyses in a parasitic nematode, and provides insight into the genomics of ivermectin response and population structure of O. volvulus. We argue that ivermectin response is a polygenically-determined quantitative trait (QT whereby identical or related molecular pathways but not necessarily individual genes are likely to determine the extent of ivermectin response in different parasite populations. Furthermore, we propose that genetic
Patricia N Okorie
Full Text Available BACKGROUND: Nigeria has a significant burden of lymphatic filariasis (LF caused by the parasite Wuchereria bancrofti. A major concern to the expansion of the LF elimination programme is the risk of serious adverse events (SAEs associated with the use of ivermectin in areas co-endemic with Loa filariasis. To better understand this, as well as other factors that may impact on LF elimination, we used Micro-stratification Overlap Mapping (MOM to highlight the distribution and potential impact of multiple disease interventions that geographically coincide in LF endemic areas and which will impact on LF and vice versa. METHODOLOGY/PRINCIPAL FINDINGS: LF data from the literature and Federal Ministry of Health (FMoH were collated into a database. LF prevalence distributions; predicted prevalence of loiasis; ongoing onchocerciasis community-directed treatment with ivermectin (CDTi; and long-lasting insecticidal mosquito net (LLIN distributions for malaria were incorporated into overlay maps using geographical information system (GIS software. LF was prevalent across most regions of the country. The mean prevalence determined by circulating filarial antigen (CFA was 14.0% (n = 134 locations, and by microfilaria (Mf was 8.2% (n = 162 locations. Overall, LF endemic areas geographically coincided with CDTi priority areas, however, LLIN coverage was generally low (<50% in areas where LF prevalence was high or co-endemic with L. loa. CONCLUSIONS/SIGNIFICANCE: The extensive database and series of maps produced in this study provide an important overview for the LF Programme and will assist to maximize existing interventions, ensuring cost effective use of resources as the programme scales up. Such information is a prerequisite for the LF programme, and will allow for other factors to be included into planning, as well as monitoring and evaluation activities given the broad spectrum impact of the drugs used.
Full Text Available A disproportionate burden of helminthiases in human populations occurs in marginalised, low-income, and resource-constrained regions of the world, with over 1 billion people in developing areas of sub-Saharan Africa, Asia, and the Americas infected with one or more helminth species. The morbidity caused by such infections imposes a substantial burden of disease, contributing to a vicious circle of infection, poverty, decreased productivity, and inadequate socioeconomic development. Furthermore, helminth infection accentuates the morbidity of malaria and HIV/AIDS, and impairs vaccine efficacy. Polyparasitism is the norm in these populations, and infections tend to be persistent. Hence, there is a great need to reduce morbidity caused by helminth infections. However, major deficiencies exist in diagnostics and interventions, including vector control, drugs, and vaccines. Overcoming these deficiencies is hampered by major gaps in knowledge of helminth biology and transmission dynamics, platforms from which to help develop such tools. The Disease Reference Group on Helminths Infections (DRG4, established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR, was given the mandate to review helminthiases research and identify research priorities and gaps. In this review, we provide an overview of the forces driving the persistence of helminthiases as a public health problem despite the many control initiatives that have been put in place; identify the main obstacles that impede progress towards their control and elimination; and discuss recent advances, opportunities, and challenges for the understanding of the biology, epidemiology, and control of these infections. The helminth infections that will be discussed include: onchocerciasis, lymphatic filariasis, soil-transmitted helminthiases, schistosomiasis, food-borne trematodiases, and taeniasis/cysticercosis.
The elevation of the morbility of tropical diesases in Chinese people indicates that the medical staffs are not familiar with these diseases,nor the vectors which transmit the tropical diseases. This paper aims to introduce some insect vectors which can transmitt main tropical diseases,such as malaria,lymphatic filariasis,dengue fever,yellow fever,rift valley fever and west nile fever can be transmitted by mosquitos, the loaiasis can be transmitted by chrysops.the onchocerciasis can be transmitted by simuliidae,the leishmaniasis can be transmitted by phlebotomines.the african trypanosomiasis can be transmitted by glossina and the american trypanosomiasis can be transmitted by triatomine.%随着国际交往的的日益频繁,来我国的外国人群中,以及我国赴热带地域国家归国的人群中罹患热带病者日益增多,而广大医务人员对热带病诊治还不熟悉,对引起这些疾病的媒介昆虫就更加陌生.现以疾病为序,对传播疟疾、淋巴丝虫病、登革热、黄热病、立夫特山谷热、西尼罗热的媒介蚊；传播盘尾丝虫病的蚋,传播罗阿丝虫病的斑虻,传播利什曼病的白蛉,传播非洲锥虫病的舌蝇、美洲锥虫病的锥蝽进行简述.
Mwinzi Pauline NM
Full Text Available Abstract Background Schistosome and soil-transmitted helminth (STH infections are recognized as major global public health problems, causing severe and subtle morbidity, including significant educational and nutritional effects in children. Although effective and safe drugs are available, ensuring access to these drugs by all those at risk of schistosomiasis and STHs is still a challenge. Community-directed intervention (CDI has been used successfully for mass distribution of drugs for other diseases such as onchocerciasis and lymphatic filariasis. A national control programme is yet to be instituted in Kenya and evidence for cost-effective strategies for reaching most affected communities is needed. This study evaluated the effectiveness and feasibility of the CDI strategy in the control of schistosomiasis and STHs, in East Uyoma location, Rarieda district, a community of western Kenya that is highly endemic for both infections. Results Pre-treatment prevalence of S. mansoni averaged 17.4% (range 5-43% in the entire location. Treatment coverage in different villages ranged from 54.19 to 96.6% by community drug distributor (CDD records. Assessment from a household survey showed coverage of 52.3 -91.9% while the proportion of homesteads (home compounds covered ranged from 54.9-98.5%. Six months after one round of drug distribution, the prevalence levels of S. mansoni, hookworm and Trichuris trichura infections were reduced by 33.2%, 69.4% and 42.6% respectively. Conclusions This study shows that CDI is an accepted and effective strategy in the mass treatment of schistosomiasis and STH infections in resource constrained communities in Kenya and may be useful in similar communities elsewhere. A controlled trial comparing CDI and school based mass drug administration to demonstarte their relative advantages is ongoing.
The high prevalence neglected tropical diseases (NTDs) exhibit a global disease burden that exceeds malaria, tuberculosis, and other better known global health conditions; they also represent a potent force in trapping the world's poorest people in poverty. Through extremely low cost national programs of disease mapping and mass drug administration (MDA) for the seven most common NTDs, integrated NTD control and elimination efforts are now in place in more than 14 countries through the support of the United States Agency for International Development (USAID), the British Department for International Development (DFID), and the Global Network for NTDs and its partners. The World Health Organization (WHO) estimates that in 2008 some 670 million people in 75 countries received NTD treatments through these and other sponsored programs. With continued successes the next decade could witness the global elimination of blinding trachoma, human Africa trypanosomiasis (HAT), lymphatic filariasis (LF), onchocerciasis, trachoma, and leprosy as public health problems, in addition to the eradication of dracunculiasis. For other high prevalence NTDs, including hookworm infection, schistosomiasis, Chagas disease and leishmaniasis, new drugs and vaccines may still be required. Increasingly it is recognized that the high prevalence NTDs exhibit extensive geographic overlap and polyparasitism is commonly found throughout the world's low income countries. Therefore, global elimination will also require integrated packages of drugs together with vaccine-linked chemotherapy. Ultimately, the global elimination of the high prevalence NTDs will require continued large-scale support from the U.S. Government and selected European governments, however, the emerging market economies, such as Brazil, China, India, Mexico, and Nigeria, and wealthy countries in the Middle East will also have to substantially contribute. Copyright © 2011 Elsevier Ltd. All rights reserved.
Full Text Available Background & objectives: Mass administration of ivermectin drug was carried out annually between 1995 and 2001 in three villages that were endemic for onchocerciasis in the Lower Cross River Basin, Nigeria. The aim of this study was to evaluate the population dynamics (dispersion patterns, distribution, prevalence and intensity of Onchocerca volvulus microfilariae in their human host after six years of ivermectin treatment. Methods: A total of 1014 subjects from three rural areas in Etung Local Government Area of Cross River State, Nigeria were screened for skin microfilariae using standard parasitological method of diagnosis. Results: Ivermectin drug intervention had significantly reduced the prevalence of skin microfilariae (PMF from 69.3% pre-control to 39.3% and community microfilarial load (CMFL from 7.11 to 2.31 microfilariae per skin snip. Males (45% were significantly (p 0.05. The correlation between age-dependent parasite prevalence and mean abundance was also not significant (r = 0.42; p >0.05. The degree of dispersion as measured by variance to mean ratio (VMR, coefficient of variation (CV and exponent ‘K’ of the negative binomial model of distribution showed that the parasite aggregated, clumped and overdispersed in their human host. The relative index of potential infection of each age group showed that adults between the age of 21 and 50 yr accounted for 52.7% of microfilariae positive cases. Interpretation & conclusion: Aggregated and overdispersion of O. volvulus observed in this study showed that active transmission could still be going on, because the tendency of the vector, Simulium damnosum ingesting more microfilariae was high due to the aggregated and overdispersed nature of the parasite with its host.
Ramachandran, Sabarinathan; Kumar, Mishra Pankaj; Rami, Reddy Maryada Venkata; Chinnaiah, Harinath Basker; Nutman, Thomas; Kaliraj, Perumal; McCarthy, James
Genes from the infective stage of lymphatic filarial parasites expressed at the time of host invasion have been identified as potential vaccine candidates. By screening an L3 cDNA library with sera from uninfected longstanding residents of an area endemic for onchocerciasis, so-called "endemic normals" (EN), we have cloned and characterized one such gene termed the abundant larval transcript two (ALT-2). The stage specificity of ALT-2 gene transcription and protein synthesis was confirmed by PCR using genespecific primers, and by western blot analysis of protein extracts from various stages of the parasite life cycle using specific antisera. Significant differences in antibody response to the recombinant ALT-2 were observed in endemic populations with differing clinical manifestations of lymphatic filariasis with an antibody response present in sera from 18 of 25 (72%) EN subjects compared to 9 of 25 (36%) with subclinical microfilaracmia (MF) and 14 of 25 (52%) of those with chronic lymphatic obstruction (CP) (P=0.01 for comparison of EN to CP or to MF). This differential responsiveness suggests that the protective immunity postulated to account for their uninfected status might be associated with a response to this protein. When the utility of ALT-2 as a vaccine candidate was tested in a murine model using either recombinant protein or a DNA vaccine construct, statistically significant protection was observed when compared to a control filarial gene product expressed across all stages of the parasite lifecycle (SXP-1; P=0.02 for protein and P=0.01 for the DNA vaccine) or compared to adjuvant alone. This level of protection indicates that this vaccine is a promising candidate for further development.
Hotez, Peter J; Woc-Colburn, Laila; Bottazzi, Maria Elena
A review of the literature since 2009 reveals a staggering health and economic burden resulting from neglected tropical diseases in Panama and the six countries of Central America (referred to collectively here as 'Central America'). Particularly at risk are the 10.2million people in the region who live on less than $2 per day, mostly in Guatemala, Honduras, Nicaragua and El Salvador. Indigenous populations are especially vulnerable to neglected tropical diseases. Currently, more than 8million Central American children require mass drug treatments annually (or more frequently) for their intestinal helminth infections, while vector-borne diseases are widespread. Among the vector-borne parasitic infections, almost 40% of the population is at risk for malaria (mostly Plasmodium vivax infection), more than 800,000 people live with Chagas disease, and up to 39,000 people have cutaneous leishmaniasis. In contrast, an important recent success story is the elimination of onchocerciasis from Central America. Dengue is the leading arbovirus infection with 4-5million people affected annually and hantavirus is an important rodent-borne viral neglected tropical disease. The leading bacterial neglected tropical diseases include leptospirosis and trachoma, for which there are no disease burden estimates. Overall there is an extreme dearth of epidemiological data on neglected tropical diseases based on active surveillance as well as estimates of their economic impact. Limited information to date, however, suggests that neglected tropical diseases are a major hindrance to the region's economic development, in both the most impoverished Central American countries listed above, as well as for Panama and Costa Rica where a substantial (but largely hidden) minority of people live in extreme poverty.
Slatko Barton E
Full Text Available Abstract Background Lymphatic filariasis and onchocerciasis are debilitating diseases caused by filarial nematodes. Disease pathogenesis is induced by inflammatory responses following the death of the parasite. Wolbachia endosymbionts of filariae are potent inducers of innate and adaptive inflammation and bacterial lipoproteins have been identified as the ligands that bind toll-like receptors (TLR 2 and TLR6. Lipoproteins are important structural and functional components of bacteria and therefore enzymes involved in Wolbachia lipoprotein biosynthesis are potential chemotherapeutic targets. Results Globomycin, a signal peptidase II (LspA inhibitor, has activity against Gram-negative bacteria and a putative lspA gene has been identified from the Wolbachia genome of Brugia malayi (wBm. The amino acids required for function are strictly conserved and functionality was verified by complementation tests in a temperature-sensitive Escherichia coli lspA mutant. Also, transformation of wild type E. coli with Wolbachia lspA conferred significant globomycin resistance. A cell-based screen has been developed utilizing a Wolbachia-containing Aedes albopictus cell line to assay novel compounds active against Wolbachia. Globomycin was screened using this assay, which resulted in a dose-dependent reduction in Wolbachia load. Furthermore, globomycin was also effective in reducing the motility and viability of adult B. malayi in vitro. Conclusions These studies validate lipoprotein biosynthesis as a target in an organism for which no genetic tools are available. Further studies to evaluate drugs targeting this pathway are underway as part of the A-WOL drug discovery and development program.
Colin D Mathers
Full Text Available Reliable, comparable information about the main causes of disease and injury in populations, and how these are changing, is a critical input for debates about priorities in the health sector. Traditional sources of information about the descriptive epidemiology of diseases, injuries, and risk factors are generally incomplete, fragmented, and of uncertain reliability and comparability. The Global Burden of Disease (GBD study has provided a conceptual and methodological framework to quantify and compare the health of populations using a summary measure of both mortality and disability, the disability-adjusted life year (DALY.This paper describes key features of the Global Burden of Disease analytic approach, which provides a standardized measurement framework to permit comparisons across diseases and injuries, as well as risk factors, and a systematic approach to the evaluation of data. The paper describes the evolution of the GBD, starting from the first study for the year 1990, summarizes the methodological improvements incorporated into GBD revisions for the years 2000-2004 carried out by the World Health Organization, and examines priorities and issues for the next major GBD study, funded by the Bill & Melinda Gates Foundation, and commencing in 2007.The paper presents an overview of summary results from the Global Burden of Disease study 2002, with a particular focus on the neglected tropical diseases, and also an overview of the comparative risk assessment for 26 global risk factors. Taken together, trypanosomiasis, Chagas disease, schistosomiasis, leishmaniasis, lymphatic filariasis, onchocerciasis, intestinal nematode infections, Japanese encephalitis, dengue, and leprosy accounted for an estimated 177,000 deaths worldwide in 2002, mostly in sub-Saharan Africa, and about 20 million DALYs, or 1.3% of the global burden of disease and injuries. Further research is currently underway to revise and update these estimates.
A.O . Oduntan
Full Text Available A recent review of the causes and prevalence of low vision and blindness world wide is lack-ing. Such review is important for highlighting the causes and prevalence of visual impairment in the different parts of the world. Also, it is important in providing information on the types and magnitude of eye care programs needed in different parts of the world. In this article, the causes and prevalence of low vision and blind-ness in different parts of the world are reviewed and the socio-economic and psychological implications are briefly discussed. The review is based on an extensive review of the litera-ture using computer data bases combined with review of available national, regional and inter-national journals. Low vision and blindness are more prevalent in the developing countries than in the developed ones. Generally, the causes and prevalence of the conditions vary widely in different parts of the world and even within the same country. World wide, cataract is the most common cause of blindness and low vision among adults and elderly. Infectious diseases such as trachoma and onchocerciasis result-ing in low vision and blindness are peculiar to Africa, Asia and South America. Hereditary and congenital conditions are the most common causes of low vision and blindness among chil-dren worldwide.
Cupp, E W; Cupp, M S
When blood-feeding, black flies introduce secretions into the feeding lesion that act in a coordinated manner on the 3 arms of the vertebrate hemostatic system (platelet aggregation, coagulation, and vasoconstriction). Apyrase activity inhibits platelet aggregation and is ubiquitous in the saliva of black flies, although activity per gland varies by species and has a positive association with anthropophagy. Anticoagulants target components in the final common pathway of the coagulation cascade, including factors V, Xa, and II (thrombin). The antithrombin salivary protein may exert a redundant effect by inhibiting the role of thrombin in platelet aggregation. Antithrombin presence and activity also varies among black fly species, and exhibits a positive correlation with zoophagy. Vasodilation of capillaries to increase blood supply to the feeding wound appears to be an important requirement for Simulium spp., because substantial erythema-inducing activity, has been demonstrated in salivary glands of all New World species examined. Salivary glands of Simulium ochraceum (Walker), a highly anthropophilic vector of Onchocerca volvulus (Leuckhart), contain greater vasodilator activity than several other species, including S. metallicum Bellardi, a secondary zoophagic vector of human onchocerciasis. Simulium vittatum Zetterstedt saliva affects immune cell responses and cytokine production. The ability of the saliva to modulate components of the host immune system provides an opportunity for enhancing transmission of pathogens during bloodfeeding. Thus, the likely possibility that effective pathogen transmission relies on vector saliva may complement present efforts aimed at target epitopes of O. volvulus or identify additional molecules to be investigated as part of a "river blindness" vaccine cocktail. Components in saliva also may enhance the transmission of other microbial agents either by a cofeeding process similar to that observed in ixodid ticks or through rupture
Peter J Hotez
Full Text Available The neglected tropical diseases (NTDs are the most common conditions affecting the poorest 500 million people living in sub-Saharan Africa (SSA, and together produce a burden of disease that may be equivalent to up to one-half of SSA's malaria disease burden and more than double that caused by tuberculosis. Approximately 85% of the NTD disease burden results from helminth infections. Hookworm infection occurs in almost half of SSA's poorest people, including 40-50 million school-aged children and 7 million pregnant women in whom it is a leading cause of anemia. Schistosomiasis is the second most prevalent NTD after hookworm (192 million cases, accounting for 93% of the world's number of cases and possibly associated with increased horizontal transmission of HIV/AIDS. Lymphatic filariasis (46-51 million cases and onchocerciasis (37 million cases are also widespread in SSA, each disease representing a significant cause of disability and reduction in the region's agricultural productivity. There is a dearth of information on Africa's non-helminth NTDs. The protozoan infections, human African trypanosomiasis and visceral leishmaniasis, affect almost 100,000 people, primarily in areas of conflict in SSA where they cause high mortality, and where trachoma is the most prevalent bacterial NTD (30 million cases. However, there are little or no data on some very important protozoan infections, e.g., amebiasis and toxoplasmosis; bacterial infections, e.g., typhoid fever and non-typhoidal salmonellosis, the tick-borne bacterial zoonoses, and non-tuberculosis mycobaterial infections; and arboviral infections. Thus, the overall burden of Africa's NTDs may be severely underestimated. A full assessment is an important step for disease control priorities, particularly in Nigeria and the Democratic Republic of Congo, where the greatest number of NTDs may occur.
Nyongbela Kennedy D
Full Text Available Abstract Background The current treatment of onchocerciasis relies on the use of ivermectin which is only microfilaricidal and for which resistant parasite strains of veterinary importance are increasingly being detected. In the search for novel filaricides and alternative medicines, we investigated the selective activity of crude extracts of Margaritaria discoidea and Homalium africanum on Onchocerca ochengi, a model parasite for O. volvulus. These plants are used to treat the disease in North West Cameroon. Methods Sixteen crude extracts were prepared from various parts of M. discoidea and H. africanum using different organic solvents. The filaricidal activities were determined in vitro. Cytotoxicity of the active extracts was assessed on monkey kidney epithelial cells in vitro and the selectivity indices (SI of the extracts determined. Acute toxicity of the promising extracts was investigated in mice. Results Four out of the 16 extracts showed microfilaricidal activity based on motility reduction, whereas, none showed macrofilaricidal activity based on the MTT/formazan assay. The methylene chloride extract of H. africanum leaves (HLC recorded the lowest IC50 of 31.25 μg/mL and an IC100 of 62.5 μg/mL. The SI for the active extracts ranged from 0.5 - 2.63. No form of acute toxicity was observed in mice. Phytochemical analysis revealed the presence of anthraquinones, sterols and terpenoids in the promising extracts. Conclusions The non-polar extracts of M. discoidea and H. africanum are potential sources of new microfilaricidal lead compounds, and the results support their use in traditional medicine.
Full Text Available Administration of ivermectin (IVM as part of mass drug administration (MDA campaigns for onchocerciasis and/or lymphatic filariasis (LF has been suspended in areas co-endemic for Loa loa due to severe post-treatment adverse events (SAEs associated with high-burden of infection (>30,000 mf/ml. One simple approach for preventing SAEs is to identify and exclude individuals at risk from MDA. Here, we describe a repurposed hand-held automated cell counter (Scepter 2.0; HHAC as a rapid, point-of-care method for quantifying microfilariae (mf in the blood of infected individuals.The quantification of microfilarial levels in blood of naturally infected humans, experimentally infected baboons, or mf-spiked human blood was tested using a microfluidic-based automated counter and compared to traditional calibrated thick-smears. We demonstrate that mf can be quantified in 20 µl of whole blood following lysis with 10% saponin within a minute of obtaining blood. There was a highly significant concordance between the counts obtained by the HHAC and those by microscopy for mf densities of >5,000 (p30,000 per ml (p<0.0001, r(c = 0.90. Preliminary proof of concept field studies in Cameroon with 20 µl of blood from L. loa infected humans (n = 22 and baboons (n = 4 also demonstrated a significantly high concordance (p<0.0001, r(c = 0.89 with calibrated thick blood smears counts.A repurposed HHAC is a portable, sensitive, rapid, point-of-care and quantitative tool to identify individuals with high levels of L. loa mf that put them at risk for SAEs following MDA. In addition, it provides ease of data storage and accessibility.
Homeida, Mamoun M; Malcolm, Stephen B; ElTayeb, A Z; Eversole, Rob R; Elassad, Asma S; Geary, Timothy G; Ali, Magdi M; Mackenzie, Charles D
There is concern that extraneous factors, such as food and drink, may alter the pharmacodynamics of Mectizan(®) (ivermectin) in patients receiving this important anti-parasitic drug, and thus might put such individuals in danger of serious adverse events. The effects of a common local alcohol-containing beverage and a local food on plasma levels of ivermectin were studied in Sudanese volunteers after administration of the standard dose used in mass drug administration programs for onchocerciasis and filariasis. Plasma levels of ivermectin at various time points (0-48h) after administration of ivermectin were ascertained by HPLC assay in ten volunteers given 150μgkg(-1) ivermectin together with either a local sorghum-based food ('assida'), or a locally brewed alcoholic beverage ('arangi' made from sorghum grain) or in those who were fasting. Maximum mean (±SD) plasma levels of ivermectin (67±49ngml(-1)) were reached within 2h in fasting patients, and had dropped to 26±20ngml(-1) after 30h. The coadministration of local food or alcoholic beverage did not cause an increase in ivermectin plasma levels above those observed in people who were fasting. However, at 2h after ivermectin administration, patients given alcohol had significantly lower plasma ivermectin levels than fed patients or fasting patients. There were no significant differences among treatments for AUC0-30, Cmax, or tmax, and so the coadministration of local food or alcoholic beverage did not cause any change in pharmacokinetic parameters of ivermectin in the plasma in comparison with fasting. None of the measured levels of plasma ivermectin were greater than those reported in previous studies with this compound. These findings do not support the hypothesis that acute intake of alcohol is an important factor in the development of the serious adverse reactions that can occur during the treatment of loaisis patients with ivermectin (Mectizan(®)).
Kim, Young Eun; Remme, Jan H F; Steinmann, Peter; Stolk, Wilma A; Roungou, Jean-Baptiste; Tediosi, Fabrizio
River blindness (onchocerciasis) causes severe itching, skin lesions, and vision impairment including blindness. More than 99% of all current cases are found in sub-Saharan Africa. Fortunately, vector control and community-directed treatment with ivermectin have significantly reduced morbidity. Studies in Mali and Senegal proved the feasibility of elimination with ivermectin administration. The treatment goal is shifting from control to elimination in endemic African regions. Given limited resources, national and global policymakers need a rigorous analysis comparing investment options. For this, we developed scenarios for alternative treatment goals and compared treatment timelines and drug needs between the scenarios. Control, elimination, and eradication scenarios were developed with reference to current standard practices, large-scale studies, and historical data. For each scenario, the timeline when treatment is expected to stop at country level was predicted using a dynamical transmission model, and ivermectin treatment needs were predicted based on population in endemic areas, treatment coverage data, and the frequency of community-directed treatment. The control scenario requires community-directed treatment with ivermectin beyond 2045 with around 2.63 billion treatments over 2013-2045; the elimination scenario, until 2028 in areas where feasible, but beyond 2045 in countries with operational challenges, around 1.48 [corrected] billion treatments; and the eradication scenario, lasting until 2040, around 1.30 billion treatments. The eradication scenario is the most favorable in terms of the timeline of the intervention phase and treatment needs. For its realization, strong health systems and political will are required to overcome epidemiological and political challenges.
Full Text Available Abstract Background Neglected tropical diseases (NTDs are a group of chronic parasitic diseases and related conditions that are the most common diseases among the 2·7 billion people globally living on less than US$2 per day. In response to the growing challenge of NTDs, Ethiopia is preparing to launch a NTD Master Plan. The purpose of this review is to underscore the burden of NTDs in Ethiopia, highlight the state of current interventions, and suggest ways forward. Results This review indicates that NTDs are significant public health problems in Ethiopia. From the analysis reported here, Ethiopia stands out for having the largest number of NTD cases following Nigeria and the Democratic Republic of Congo. Ethiopia is estimated to have the highest burden of trachoma, podoconiosis and cutaneous leishmaniasis in sub-Saharan Africa (SSA, the second highest burden in terms of ascariasis, leprosy and visceral leishmaniasis, and the third highest burden of hookworm. Infections such as schistosomiasis, trichuriasis, lymphatic filariasis and rabies are also common. A third of Ethiopians are infected with ascariasis, one quarter is infected with trichuriasis and one in eight Ethiopians lives with hookworm or is infected with trachoma. However, despite these high burdens of infection, the control of most NTDs in Ethiopia is in its infancy. In terms of NTD control achievements, Ethiopia reached the leprosy elimination target of 1 case/10,000 population in 1999. No cases of human African trypanosomiasis have been reported since 1984. Guinea worm eradication is in its final phase. The Onchocerciasis Control Program has been making steady progress since 2001. A national blindness survey was conducted in 2006 and the trachoma program has kicked off in some regions. Lymphatic Filariasis, podoconiosis and rabies mapping are underway. Conclusion Ethiopia bears a significant burden of NTDs compared to other SSA countries. To achieve success in integrated control of
[Evaluation of the efficacity of coconut (Cocos nucifera), palm nut (Eleais guineensis) and gobi (Carapa procera) lotions and creams in indivirual protection against Simulium damnosum s.l. bites in Côte d'Ivoire].
Sylla, M; Konan, L; Doannio, J M; Traoré, S
With the interruption of larva treatments done by OCP as part of onchocerciasis control in West Africa, Simulium came back in abundance in forest regions and savannah fertile valleys. In addition to the severe discomfort, nuisance by Simulium is in certain cases incompatible with land use. Since ground treatment of larval breading sites using insecticides is not always possible or efficient, it is therefore a necessity to develop other methods among which individual protection against Simulium bites. The general objective of our study was to evaluate different vegetable oil compound repellent formulas against Simulium bites. Activities were carried out in savannah zone (Niakaramandougou) and in forest zone (Soubré) in Côte d'Ivoire. The methodology consisted in catching blackflies on volunteers whose legs were rubbed with a repellent. Gobi raw oil and coconut, palm nut and gobi formulas (lotions and creams) were tested. During each session, which lasted from 07:00 am to 12:00 and from 03:00 pm to 06:00 pm, one person did not apply any repellent and was used as the control person. The results of our experimentations show that for a given zone (savannah, forest), a repellent (coconut, palm nut, gobi) and a compound (shea butter, vaseline), there is no significant difference between protection rates obtained with lotions (maximum: 21 bites/person/day) and those obtained with creams (maximum: 30 bites/person/day). In other respects, the lotion of a given repellent seems to be efficient in savannah as in the forest, in protecting against Simulium bites. It is the same situation with creams. So, repellents can be an efficient solution against Simulium nuisance. However, experimentations should continue to confirm the high repellency of tested formulas, proceed to the identification of principles and evaluate the toxicity and irritant effect of repellents to be applied on the skin.
Konate, M K
The population, health, and development project in Mali (PSD-M) hypothesized that the construction of the Selingue dam would probably improve the income of the populations, cause socio-cultural changes, and degrade the environment. The prevalence of urinary schistosomiasis decreased after construction while the prevalence of intestinal schistosomiasis increased. The prevalence of onchocerciasis fell from 3.6% to 0.2% during 1980-1983. PSD-Mali could not adequately follow up on other parasitic diseases. Information on consumption of fish by the fishermen themselves was unavailable. PSD-Mali did learn, however, that fishing for self-consumption was very much lower than commercial fishing. Fish sales comprised the greatest source of income, so fishing contributed somewhat to improvement of living conditions. Fishing has become a microindustry for the indigenous women, practiced with rudimentary means, with the creation of the artificial lake. The Office for Exploitation of Resources of the Upper Niger lends itself to fishing activities which encourages migration of ethnic fishermen to the Selingue zone. Income-related data were not better available after the dam than before, except for some data related to commercialization of fresh fish. Environmental degradation continues as predicted by PSD-M, which is contradictory to rural practices in the zone. In the past, land was left fallow for several years. 1350 hectares downstream from the dam, 68.7% of which is favorable for growing rice, is not irrigable. Construction of access roads as well as the opening of new tracks allowed deforestation, but the selling of wood for heating, of charcoal, and of bamboo has resulted in a comfortable income. These findings show that there is still need for evaluation of different aspects of life of the population concerned.
Full Text Available We report results from the first genome-wide application of a rational drug target selection methodology to a metazoan pathogen genome, the completed draft sequence of Brugia malayi, a parasitic nematode responsible for human lymphatic filariasis. More than 1.5 billion people worldwide are at risk of contracting lymphatic filariasis and onchocerciasis, a related filarial disease. Drug treatments for filariasis have not changed significantly in over 20 years, and with the risk of resistance rising, there is an urgent need for the development of new anti-filarial drug therapies. The recent publication of the draft genomic sequence for B. malayi enables a genome-wide search for new drug targets. However, there is no functional genomics data in B. malayi to guide the selection of potential drug targets. To circumvent this problem, we have utilized the free-living model nematode Caenorhabditis elegans as a surrogate for B. malayi. Sequence comparisons between the two genomes allow us to map C. elegans orthologs to B. malayi genes. Using these orthology mappings and by incorporating the extensive genomic and functional genomic data, including genome-wide RNAi screens, that already exist for C. elegans, we identify potentially essential genes in B. malayi. Further incorporation of human host genome sequence data and a custom algorithm for prioritization enables us to collect and rank nearly 600 drug target candidates. Previously identified potential drug targets cluster near the top of our prioritized list, lending credibility to our methodology. Over-represented Gene Ontology terms, predicted InterPro domains, and RNAi phenotypes of C. elegans orthologs associated with the potential target pool are identified. By virtue of the selection procedure, the potential B. malayi drug targets highlight components of key processes in nematode biology such as central metabolism, molting and regulation of gene expression.
Barda, Beatrice; Coulibaly, Jean T.; Puchkov, Maxim; Huwyler, Jörg; Hattendorf, Jan; Keiser, Jennifer
Background Schistosomiasis affects millions of people, yet treatment options are limited. The antimalarial Synriam (piperaquine 150 mg/arterolane 750 mg) and the anthelminthic moxidectin revealed promising antischistosomal properties in preclinical or clinical studies. Methodology We conducted two single-blind, randomized exploratory Phase 2 trials in Schistosoma mansoni and S. haematobium-infected adolescents in northern and central Côte d’Ivoire. Our primary endpoints were cure rates (CRs) and egg reduction rates (ERRs) based on geometric mean and safety. Each subject was asked to provide two stool samples (S. mansoni trial) for Kato-Katz analysis or three urine samples (S. haematobium trial) for urine filtration and one finger prick for malaria screening at baseline and follow-up. Participants were randomly assigned to either moxidectin, Synriam, Synriam plus praziquantel or praziquantel. Principal Findings 128 adolescents (age: 12–17 years) were included in each study. Against S. haematobium moxidectin and Synriam revealed low efficacy. On the other hand, Synriam plus praziquantel and praziquantel yielded CRs of 60.0% and 38.5% and ERRs of 96.0% and 93.5%, respectively. CRs observed in the treatment of S. mansoni were 13.0%, 6.7%, 27.0%, and 27.6% for moxidectin, Synriam, Synriam plus praziquantel and praziquantel, respectively. ERRs ranged from 64.9% (Synriam) to 87.5% (praziquantel). Conclusion/Significance Synriam and moxidectin show low efficacy against S. haematobium, hence an ancillary benefit is not expected when these drugs are used for treating onchocerciasis and malaria in co-endemic settings. Further studies are needed to corroborate our findings that moxidectin and Synriam show moderate ERRs against S. mansoni. PMID:27636542
Cladistic analysis of the Neotropical genera Cerqueirellum Py-Daniel, 1983, Coscaroniellum Py-Daniel, 1983 and Shelleyellum Py-Daniel & Pessoa, 2005 (Diptera: Simuliidae Análise cladística dos gêneros neotropicais Cerqueirellum Py-Daniel, 1983, Coscaroniellum Py-Daniel, 1983 e Shelleyellum Py-Daniel & Pessoa, 2005 (Diptera: Simuliidae
Felipe Arley Costa Pessoa
Full Text Available Females of simuliid black flies are haematophagous insects and vectors of several pathogenic agents of human diseases such as the filarial worms Mansonella ozzardi and Onchocerca volvulus. The genus Cerqueirellum is one of the most important groups of vectors of mansonellosis and onchocerciasis diseases in South America, and the genera Coscaroniellum and Shelleyellum are phylogenetically close to Cerqueirellum. There is not yet an agreement among authors about the generic classification of the species which compose these three genera, being all lumped by some taxonomists within Psaroniocompsa. A cladistic analysis of all species of Coscaroniellum, Cerqueirellum, and Shelleyellum, based on 41 morphological characters were done. Species closely related to Cerqueirellum were included in the analysis. The genera Cerqueirellum, Coscaroniellum and Shelleyellum were demonstrated as consistent basal entities and well-defined monophyletic clades.As fêmeas de piuns ou borrachudos da família Simuliidae são hematófagas e vetoras de diversos patógenos, destacando-se os vermes filarióides Mansonella ozzardi e Onchocerca volvulus. Dentre os grupos supra-específicos que são vetores de mansonelose e oncocercose na América do Sul, destaca-se o gênero Cerqueirellum. Os gêneros Coscaroniellum e Shelleyellum são filogeneticamente muito próximos a Cerqueirellum. Não existia concordância quanto à validade de Cerqueirellum e Coscaroniellum como clados supra-específicos, sendo ambos os gêneros incluídos, por uma escola taxonômica, como grupos de espécies em Psaroniocompsa. Neste trabalho é feita uma análise filogenética baseada em caracteres morfológicos dos três gêneros.. Os gêneros Cerqueirellum, Coscaroniellum e Shelleyellum. apresentaram-se como entidades basais válidas, consistentes e monofiléticas.
Hotez, Peter J; Dumonteil, Eric; Heffernan, Michael J; Bottazzi, Maria E
An estimated 100 million people in the Latin American and Caribbean (LAC) region live on less than US$2 per day, while another 46 million people in the US live below that nation's poverty line. Almost all of the 'bottom 100 million' people suffer from at least one neglected tropical disease (NTD), including one-half of the poorest people in the region infected with hookworms, 10% with Chagas disease, and up to 1-2% with dengue, schistosomiasis, and/or leishmaniasis. In the US, NTDs such as Chagas disease, cysticercosis, toxocariasis, and trichomoniasis are also common among poor populations. These NTDs trap the poorest people in the region in poverty, because of their impact on maternal and child health, and occupational productivity. Through mass drug administration (MDA), several NTDs are on the verge of elimination in the Americas, including lymphatic filariasis, onchocerciasis, trachoma, and possibly leprosy. In addition, schistosomiasis may soon be eliminated in the Caribbean. However, for other NTDs including hookworm infection, Chagas disease, dengue, schistosomiasis, and leishmaniasis, a new generation of 'anti-poverty vaccines' will be required. Several vaccines for dengue are under development by multinational pharmaceutical companies, whereas others are being pursued through non-profit product development partnerships (PDPs), in collaboration with developing country manufacturers in Brazil and Mexico. The Sabin Vaccine Institute PDP is developing a primarily preventive bivalent recombinant human hookworm vaccine, which is about to enter phase 1 clinical testing in Brazil, as well as a new therapeutic Chagas disease vaccine in collaboration with several Mexican institutions. The Chagas disease vaccine would be administered to seropositive patients to delay or prevent the onset of Chagasic cardiomyopathy (secondary prevention). Together, MDA and the development of new anti-poverty vaccines afford an opportunity to implement effective control and
Young Eun Kim
Full Text Available River blindness (onchocerciasis causes severe itching, skin lesions, and vision impairment including blindness. More than 99% of all current cases are found in sub-Saharan Africa. Fortunately, vector control and community-directed treatment with ivermectin have significantly reduced morbidity. Studies in Mali and Senegal proved the feasibility of elimination with ivermectin administration. The treatment goal is shifting from control to elimination in endemic African regions. Given limited resources, national and global policymakers need a rigorous analysis comparing investment options. For this, we developed scenarios for alternative treatment goals and compared treatment timelines and drug needs between the scenarios. Control, elimination, and eradication scenarios were developed with reference to current standard practices, large-scale studies, and historical data. For each scenario, the timeline when treatment is expected to stop at country level was predicted using a dynamical transmission model, and ivermectin treatment needs were predicted based on population in endemic areas, treatment coverage data, and the frequency of community-directed treatment. The control scenario requires community-directed treatment with ivermectin beyond 2045 with around 2.63 billion treatments over 2013-2045; the elimination scenario, until 2028 in areas where feasible, but beyond 2045 in countries with operational challenges, around 1.48 [corrected] billion treatments; and the eradication scenario, lasting until 2040, around 1.30 billion treatments. The eradication scenario is the most favorable in terms of the timeline of the intervention phase and treatment needs. For its realization, strong health systems and political will are required to overcome epidemiological and political challenges.
Frempong, Kwadwo K.; Walker, Martin; Cheke, Robert A.; Tetevi, Edward Jenner; Gyan, Ernest Tawiah; Owusu, Ebenezer O.; Wilson, Michael D.; Boakye, Daniel A.; Taylor, Mark J.; Biritwum, Nana-Kwadwo; Osei-Atweneboana, Mike; Basáñez, María-Gloria
Background. Several African countries have adopted a biannual ivermectin distribution strategy in some foci to control and eliminate onchocerciasis. In 2010, the Ghana Health Service started biannual distribution to combat transmission hotspots and suboptimal responses to treatment. We assessed the epidemiological impact of the first 3 years of this strategy and quantified responses to ivermectin over 2 consecutive rounds of treatment in 10 sentinel communities. Methods. We evaluated Onchocerca volvulus community microfilarial intensity and prevalence in persons aged ≥20 years before the first, second, and fifth (or sixth) biannual treatment rounds using skin snip data from 956 participants. We used longitudinal regression modeling to estimate rates of microfilarial repopulation of the skin in a cohort of 217 participants who were followed up over the first 2 rounds of biannual treatment. Results. Biannual treatment has had a positive impact, with substantial reductions in infection intensity after 4 or 5 rounds in most communities. We identified 3 communities—all having been previously recognized as responding suboptimally to ivermectin—with statistically significantly high microfilarial repopulation rates. We did not find any clear association between microfilarial repopulation rate and the number of years of prior intervention, coverage, or the community level of infection. Conclusions. The strategy of biannual ivermectin treatment in Ghana has reduced O. volvulus microfilarial intensity and prevalence, but suboptimal responses to treatment remain evident in a number of previously and consistently implicated communities. Whether increasing the frequency of treatment will be sufficient to meet the World Health Organization's 2020 elimination goals remains uncertain. PMID:27001801
Maria Cristina Schneider
Full Text Available In Latin America and the Caribbean, around 195 million people live in poverty, a situation that increases the burden of some infectious diseases. Neglected diseases, in particular, are often restricted to poor, marginalized sections of the population. Tools exist to combat these diseases, making it imperative to work towards their elimination. In 2009, the Pan American Health Organization (PAHO received a mandate to support the countries in the Region in eliminating neglected diseases and other poverty-related infections. The objective of this study is to analyze the presence of selected diseases using geo-processing techniques. Five diseases with information available at the first sub-national level (states were mapped, showing the presence of the disease ("hotspots" and overlap of diseases ("major hotspots". In the 45 countries/territories (approximately 570 states of the Region, there is: lymphatic filariasis in four countries (29 states, onchocerciasis in six countries (25 states, schistosomiasis in four countries (39 states, trachoma in three countries (29 states, and human rabies transmitted by dogs in ten countries (20 states. Of the 108 states with one or more of the selected diseases, 36 states present the diseases in overlapping areas ("major hotspots". Additional information about soil-transmitted helminths was included. The analysis suggests a majority of the selected diseases are not widespread and can be considered part of an unfinished agenda with elimination as a goal. Integrated plans and a comprehensive approach, ensuring access to existing diagnostic and treatment methods, and establishing a multi-sectoral agenda that addresses social determinants, including access to adequate water and sanitation, are required. Future studies can include additional diseases, socio-economic and environmental variables.
Cesbron, J Y; Hayasaki, M; Joseph, M; Lutsch, C; Grzych, J M; Capron, A
Over the past 35 yr, diethylcarbamazine (DEC) has been the most widely used agent for the treatment of filarial diseases, particularly in onchocerciasis. The microfilaricidal action of DEC has been recently shown to be mediated by blood platelets with the additional triggering of a filarial excretory Ag (FEA). This FEA could be detected by using mAb in the serum of infected patients. By using one mAb (IA2(23] directed against Onchocerca volvulus and recognizing circulating Ag (Ab1), we purified by affinity chromatography the target molecule of IA2(23) (an O. volvulus glycoprotein recognized by IA2(23) mAb). This compound had a dose-dependent effect on the cytotoxic action of DEC-treated platelets. We subsequently produced an anti-idiotype mAb to Ab1 (Ab2), and considered the possibility of replacing the O. volvulus glycoprotein recognized by IA2(23) mAb by Ab2. Ab2 was selected according to its ability to inhibit the binding of radioiodinated Ab1 to the filarial target Ag. It induced the production of anti-O. volvulus antibodies (Ab3) in rats. At a constant concentration of DEC platelets, the addition of increasing amounts of Ab2 led to a dose-dependent cytotoxic effect against parasite larvae. Experiments performed with Ab2 on detergent solubilized surface proteins of platelets identified four bands of Mr 18, 26, 43.5, and 100 kDa, supporting the idea of the presence of binding sites on the platelets for a FEA required for the microfilaricidal cytotoxicity of DEC-treated platelets.
Voronin, Denis; Bachu, Saheed; Shlossman, Michael; Unnasch, Thomas R; Ghedin, Elodie; Lustigman, Sara
Wolbachia are endosymbiotic bacteria found in the majority of arthropods and filarial nematodes of medical and veterinary importance. They have evolved a wide range of symbiotic associations. In filarial nematodes that cause human lymphatic filariasis (Wuchereria bancrofti, Brugia malayi) or onchocerciasis (Onchocerca volvulus), Wolbachia are important for parasite development, reproduction and survival. The symbiotic bacteria rely in part on nutrients and energy sources provided by the host. Genomic analyses suggest that the strain of Wolbachia found in B. malayi (wBm) lacks the genes for two glycolytic enzymes--6-phosphofructokinase and pyruvate kinase--and is thus potentially unable to convert glucose into pyruvate, an important substrate for energy generation. The Wolbachia surface protein, wBm00432, is complexed to six B. malayi glycolytic enzymes, including aldolase. In this study we characterized two B. malayi aldolase isozymes and found that their expression is dependent on Wolbachia fitness and number. We confirmed by immuno-transmission electron microscopy that aldolase is associated with the Wolbachia surface. RNAi experiments suggested that aldolase-2 plays a significant role in both Wolbachia survival and embryogenesis in B. malayi. Treatment with doxycycline reduced Wolbachia fitness and increased the amount of both glucose and glycogen detected in the filarial parasite, indicating that glucose metabolism and glycogen storage in B. malayi are associated with Wolbachia fitness. This metabolic co-dependency between Wolbachia and its filarial nematode indicates that glycolysis could be a shared metabolic pathway between the bacteria and B. malayi, and thus a potential new target for anti-filarial therapy.
Evaluation of the double diffusion, enzyme immunoassay and immunoblotting techniques, for the diagnosis of human hydatid disease in tropical areas Evaluación de las técnicas de Doble Difusión, Ensayo Inmunoenzimático e Inmunoblotting en el diagnóstico de la hidatidosis humana en áreas tropicales
Full Text Available Hydatid disease in tropical areas poses a serious diagnostic problem due to the high frequence of cross-reactivity with other endemic helminthic infections. The enzyme-linked-immunosorbent assay (ELISA and the double diffusion arc 5 showed respectively a sensitivity of 73% and 57% and a specificity of 84-95% and 100%. However, the specificity of ELISA was greatly increased by using ovine serum and phosphorylcholine in the diluent buffer. The hydatic antigen obtained from ovine cyst fluid showed three main protein bands of 64,58 and 30 KDa using SDS PAGE and immunoblotting. Sera from patients with onchocerciasis, cysticercosis, toxocariasis and Strongyloides infection cross-reacted with the 64 and 58 KDa bands by immunoblotting. However, none of the analyzed sera recognized the 30 KDa band, that seems to be specific in this assay. The immunoblotting showed a sensitivity of 80% and a specificity of 100% when used to recognize the 30 KDa band.La Hidatidosis en áreas tropicales representa un serio problema diagnóstico por la alta frecuencia de reactividad cruzada con otras infecciones helmínticas. Las técnicas de inmunoensayo enzimático (ELISA y doble difusión arco 5 (DD5 mostraron una sensibilidad de 73 y 57 % y una especificidad de 84-95% y 100%, respectivamente. La especificidad en la técnica de ELISA, fue mejorada sustancialmente al emplear como diluyente de los sueros una solución buffer conteniendo suero ovino normal y fosforilcolina. En líquido obtenido de hidátides de Echinococcus granulosus de origen ovino, se demostraron tres bandas de origen proteico de 64, 58 y 30 KDa de peso molecular, empleando SDS e inmunoblotting. Sueros de pacientes con estrongiloidiasis, oncocer-cosis, toxocariasis y cisticercosis reaccionaron con las bandas de 64 y 58 KDa en inmunoblotting. Sin embargo ninguno de los sueros reconoció la banda de 30 KD, la cual parece ser específica para este ensayo. La técnica de inmunobloting empleada para poner en
Full Text Available Abstract Background Less is known about mass drug administration [MDA] for neglected tropical diseases [NTDs] than is suggested by those so vigorously promoting expansion of the approach. This paper fills an important gap: it draws upon local level research to examine the roll out of treatment for two NTDs, schistosomiasis and soil-transmitted helminths, in Uganda. Methods Ethnographic research was undertaken over a period of four years between 2005-2009 in north-west and south-east Uganda. In addition to participant observation, survey data recording self-reported take-up of drugs for schistosomiasis, soil-transmitted helminths and, where relevant, lymphatic filariasis and onchocerciasis was collected from a random sample of at least 10% of households at study locations. Data recording the take-up of drugs in Ministry of Health registers for NTDs were analysed in the light of these ethnographic and social survey data. Results The comparative analysis of the take-up of drugs among adults revealed that although most long term residents have been offered treatment at least once since 2004, the actual take up of drugs for schistosomiasis and soil-transmitted helminths varies considerably from one district to another and often also within districts. The specific reasons why MDA succeeds in some locations and falters in others relates to local dynamics. Issues such as population movement across borders, changing food supply, relations between drug distributors and targeted groups, rumours and conspiracy theories about the 'real' purpose of treatment, subjective experiences of side effects from treatment, alternative understandings of affliction, responses to social control measures and historical experiences of public health control measures, can all make a huge difference. The paper highlights the need to adapt MDA to local circumstances. It also points to specific generalisable issues, notably with respect to health education, drug distribution and
Segura-Cabrera, Aldo; Bocanegra-García, Virgilio; Lizarazo-Ortega, Cristian; Guo, Xianwu; Correa-Basurto, José; Rodríguez-Pérez, Mario A.
Onchocerciasis is a leading cause of blindness with at least 37 million people infected and more than 120 million people at risk of contracting the disease; most (99%) of this population, threatened by infection, live in Africa. The drug of choice for mass treatment is the microfilaricidal Mectizan® (ivermectin); it does not kill the adult stages of the parasite at the standard dose which is a single annual dose aimed at disease control. However, multiple treatments a year with ivermectin have effects on adult worms. The discovery of new therapeutic targets and drugs directed towards the killing of the adult parasites are thus urgently needed. The chitinase of filarial nematodes is a new drug target due to its essential function in the metabolism and molting of the parasite. Closantel is a potent and specific inhibitor of chitinase of Onchocerca volvulus (OvCHT1) and other filarial chitinases. However, the binding mode and specificity of closantel towards OvCHT1 remain unknown. In the absence of a crystallographic structure of OvCHT1, we developed a homology model of OvCHT1 using the currently available X-ray structures of human chitinases as templates. Energy minimization and molecular dynamics (MD) simulation of the model led to a high quality of 3D structure of OvCHIT1. A flexible docking study using closantel as the ligand on the binding site of OvCHIT1 and human chitinases was performed and demonstrated the differences in the closantel binding mode between OvCHIT1 and human chitinase. Furthermore, molecular dynamics simulations and free-energy calculation were employed to determine and compare the detailed binding mode of closantel with OvCHT1 and the structure of human chitinase. This comparative study allowed identification of structural features and properties responsible for differences in the computationally predicted closantel binding modes. The homology model and the closantel binding mode reported herein might help guide the rational development of
Armstrong, Stuart D.; Babayan, Simon A.; Lhermitte-Vallarino, Nathaly; Gray, Nick; Xia, Dong; Martin, Coralie; Kumar, Sujai; Taylor, David W.; Blaxter, Mark L.; Wastling, Jonathan M.; Makepeace, Benjamin L.
Filarial nematodes (superfamily Filarioidea) are responsible for an annual global health burden of ∼6.3 million disability-adjusted life-years, which represents the greatest single component of morbidity attributable to helminths affecting humans. No vaccine exists for the major filarial diseases, lymphatic filariasis and onchocerciasis; in part because research on protective immunity against filariae has been constrained by the inability of the human-parasitic species to complete their lifecycles in laboratory mice. However, the rodent filaria Litomosoides sigmodontis has become a popular experimental model, as BALB/c mice are fully permissive for its development and reproduction. Here, we provide a comprehensive analysis of excretory-secretory products from L. sigmodontis across five lifecycle stages and identifications of host proteins associated with first-stage larvae (microfilariae) in the blood. Applying intensity-based quantification, we determined the abundance of 302 unique excretory-secretory proteins, of which 64.6% were present in quantifiable amounts only from gravid adult female nematodes. This lifecycle stage, together with immature microfilariae, released four proteins that have not previously been evaluated as vaccine candidates: a predicted 28.5 kDa filaria-specific protein, a zonadhesin and SCO-spondin-like protein, a vitellogenin, and a protein containing six metridin-like ShK toxin domains. Female nematodes also released two proteins derived from the obligate Wolbachia symbiont. Notably, excretory-secretory products from all parasite stages contained several uncharacterized members of the transthyretin-like protein family. Furthermore, biotin labeling revealed that redox proteins and enzymes involved in purinergic signaling were enriched on the adult nematode cuticle. Comparison of the L. sigmodontis adult secretome with that of the human-infective filarial nematode Brugia malayi (reported previously in three independent published studies
Arlindo Serpa Filho
adopted led to a diversity of information that enabled each participant to understand the life cycle of the vectors and parasites of diseases such as onchocerciasis, mansonelliasis, malaria, leishmaniasis, schistosomiasis, and the Chagas disease. It also allowed interaction with ecological, health and environmental education issues. The training provided teachers and students with an experience on the extent of health problems in the state of Tocantins.
Molyneux David H
Full Text Available Abstract Since 2004 there has been an increased recognition of the importance of Neglected Tropical Diseases (NTDs as impediments to development. These diseases are caused by a variety of infectious agents - viruses, bacteria and parasites - which cause a diversity of clinical conditions throughout the tropics. The World Health Organisation (WHO has defined seventeen of these conditions as core NTDs. The objectives for the control, elimination or eradication of these conditions have been defined in World Health Assembly resolutions whilst the strategies for the control or elimination of individual diseases have been defined in various WHO documents. Since 2005 there has been a drive for the expanded control of these diseases through an integrated approach of mass drug administration referred to as Preventive Chemotherapy via community-based distribution systems and through schools. This has been made possible by donations from major pharmaceutical companies of quality and efficacious drugs which have a proven track record of safety. As a result of the increased commitment of endemic countries, bilateral donors and non-governmental development organisations, there has been a considerable expansion of mass drug administration. In particular, programmes targeting lymphatic filariasis, onchocerciasis, schistosomiasis, trachoma and soil transmitted helminth infections have expanded to treat 887. 8 million people in 2009. There has been significant progress towards guinea worm eradication, and the control of leprosy and human African trypanosomiasis. This paper responds to what the authors believe are inappropriate criticisms of these programmes and counters accusations of the motives of partners made in recently published papers. We provide a detailed response and update the information on the numbers of global treatments undertaken for NTDs and list the success stories to date. The paper acknowledges that in undertaking any health programme in
Full Text Available BACKGROUND: Filarial parasites (e.g., Brugia malayi, Onchocerca volvulus, and Wuchereria bancrofti are causative agents of lymphatic filariasis and onchocerciasis, which are among the most disabling of neglected tropical diseases. There is an urgent need to develop macro-filaricidal drugs, as current anti-filarial chemotherapy (e.g., diethylcarbamazine [DEC], ivermectin and albendazole can interrupt transmission predominantly by killing microfilariae (mf larvae, but is less effective on adult worms, which can live for decades in the human host. All medically relevant human filarial parasites appear to contain an obligate endosymbiotic bacterium, Wolbachia. This alpha-proteobacterial mutualist has been recognized as a potential target for filarial nematode life cycle intervention, as antibiotic treatments of filarial worms harboring Wolbachia result in the loss of worm fertility and viability upon antibiotic treatments both in vitro and in vivo. Human trials have confirmed this approach, although the length of treatments, high doses required and medical counter-indications for young children and pregnant women warrant the identification of additional anti-Wolbachia drugs. METHODS AND FINDINGS: Genome sequence analysis indicated that enzymes involved in heme biosynthesis might constitute a potential anti-Wolbachia target set. We tested different heme biosynthetic pathway inhibitors in ex vivo B. malayi viability assays and report a specific effect of N-methyl mesoporphyrin (NMMP, which targets ferrochelatase (FC, the last step. Our phylogenetic analysis indicates evolutionarily significant divergence between Wolbachia heme genes and their human homologues. We therefore undertook the cloning, overexpression and analysis of several enzymes of this pathway alongside their human homologues, and prepared proteins for drug targeting. In vitro enzyme assays revealed a approximately 600-fold difference in drug sensitivities to succinyl acetone (SA between
deC Bronsvoort Barend M
Full Text Available Abstract Background Human onchocerciasis or river blindness, caused by the filarial nematode Onchocerca volvulus, is currently controlled using the microfilaricidal drug, ivermectin. However, ivermectin does not kill adult O. volvulus, and in areas with less than 65% ivermectin coverage of the population, there is no effect on transmission. Therefore, there is still a need for a macrofilaricidal drug. Using the bovine filarial nematode O. ochengi (found naturally in African cattle, the macrofilaricidal efficacy of the modified flubendazole, UMF-078, was investigated. Methods Groups of 3 cows were treated with one of the following regimens: (a a single dose of UMF-078 at 150 mg/kg intramuscularly (im, (b 50 mg/kg im, (c 150 mg/kg intraabomasally (ia, (d 50 mg/kg ia, or (e not treated (controls. Results After treatment at 150 mg/kg im, nodule diameter, worm motility and worm viability (as measured by metabolic reduction of tetrazolium to formazan declined significantly compared with pre-treatment values and concurrent controls. There was abrogation of embryogenesis and death of all adult worms by 24 weeks post-treatment (pt. Animals treated at 50 mg/kg im showed a decline in nodule diameter together with abrogated reproduction, reduced motility, and lower metabolic activity in isolated worms, culminating in approximately 50% worm mortality by 52 weeks pt. Worms removed from animals treated ia were not killed, but exhibited a temporary embryotoxic effect which had waned by 12 weeks pt in the 50 mg/kg ia group and by 24 weeks pt in the 150 mg/kg ia group. These differences could be explained by the different absorption rates and elimination half-lives for each dose and route of administration. Conclusion Although we did not observe any signs of mammalian toxicity in this trial with a single dose, other studies have raised concerns regarding neuro- and genotoxicity. Consequently, further evaluation of this compound has been suspended. Nonetheless
Background Simulium damnosum s.l., the most important vector of onchocerciasis in Africa, is a complex of sibling species that have been described on the basis of differences in their larval polytene chromosomes. These (cyto) species differ in their geographical distributions, ecologies and epidemiological roles. In Ghana, distributional changes have been recorded as a consequence of vector control and environmental change (e.g. deforestation), with potential disease consequences. We review the distribution of cytospecies in southern Ghana and report changes observed with reference to historical data collated from 1971 to 2005 and new identifications made between 2006 and 2011. Methods/Results Larvae were collected from riverine breeding sites, fixed in Carnoy’s solution and chromosome preparations made. Cytotaxonomic identifications from 1,232 samples (including 49 new samples) were analysed. We report long-term stability in cytospecies distribution in the rivers Afram, Akrum, Pawnpawn and Pru. For the rivers Oda, Ofin and Tano we describe (for the first time) patterns of distribution. We could not detect cytospecies composition changes in the upper Pra, and the lower Pra seems to have been stable. The elimination of the Djodji form of S. sanctipauli in the Volta Region seems to have had no long-term effects on the distribution of the other cytospecies, despite an initial surge by S. yahense. There has been a recent increase in the occurrence of savannah cytospecies in the river Asukawkaw, and this might be related to continuing deforestation. Conclusions Cytospecies’ distributions have not been stable from 1971 to 2011. Although there are no obvious causes for the temporary appearance and subsequent disappearance of cytospecies in a particular location, a major influence has been vector control and migration patterns, probably explaining observed changes on the Black Volta and lower Volta rivers. Deforestation was previously implicated in an increase of
Luyendijk, Marianne; Fitzpatrick, Christopher; Niessen, Louis; Stolk, Wilma A.; Tediosi, Fabrizio; Rijnsburger, Adriana J.; Bakker, Roel; Hontelez, Jan A. C.; Richardus, Jan H.; Jacobson, Julie; de Vlas, Sake J.; Severens, Johan L.
Background Lymphatic filariasis (LF), onchocerciasis, schistosomiasis, soil-transmitted helminths (STH) and trachoma represent the five most prevalent neglected tropical diseases (NTDs). They can be controlled or eliminated by means of safe and cost-effective interventions delivered through programs of Mass Drug Administration (MDA)—also named Preventive Chemotherapy (PCT). The WHO defined targets for NTD control/elimination by 2020, reinforced by the 2012 London Declaration, which, if achieved, would result in dramatic health gains. We estimated the potential economic benefit of achieving these targets, focusing specifically on productivity and out-of-pocket payments. Methods Productivity loss was calculated by combining disease frequency with productivity loss from the disease, from the perspective of affected individuals. Productivity gain was calculated by deducting the total loss expected in the target achievement scenario from the loss in a counterfactual scenario where it was assumed the pre-intervention situation in 1990 regarding NTDs would continue unabated until 2030. Economic benefits from out-of-pocket payments (OPPs) were calculated similarly. Benefits are reported in 2005 US$ (purchasing power parity-adjusted and discounted at 3% per annum from 2010). Sensitivity analyses were used to assess the influence of changes in input parameters. Results The economic benefit from productivity gain was estimated to be I$251 billion in 2011–2020 and I$313 billion in 2021–2030, considerably greater than the total OPPs averted of I$0.72 billion and I$0.96 billion in the same periods. The net benefit is expected to be US$ 27.4 and US$ 42.8 for every dollar invested during the same periods. Impact varies between NTDs and regions, since it is determined by disease prevalence and extent of disease-related productivity loss. Conclusion Achieving the PCT-NTD targets for 2020 will yield significant economic benefits to affected individuals. Despite large
Tatiana N Docile
Full Text Available Abstract:Black flies have medical importance because some species are vectors of the Onchocerciasis and Mansonelosis, nevertheless, their ecology and potential use as bioindicators is still poorly studied in the Neotropical Region. In Brazil, bioindicators use is strongly focused in a multimetrical ecological index approach; this way, we investigated the black fly spatial distribution, in relation to abiotic factors correlated to water quality, to provide baseline information for their utilization as standalone indicators of lotic systems integrity. We have tested the hypothesis that environmental changes related to urbanization, lead to decreased abundance and loss in the number of species of the black fly fauna. The sampling was conducted in 10 urban and 10 preserved streams during the dry season (August-September of 2012, in the mountainous region of Teresópolis, State of Rio de Janeiro, Brazil. The streams were characterized for their environmental integrity conditions and physico-chemical properties of water. In each stream, five different rapid points were sampled in a section of 50 meters, 10 meters apart from each other. The black flies were sampled with a kick-net sampler on rocky substrates. The material was separated and the larvae were sorted in morphotypes, and later, the final instar specimens were dissected and identified with the help of taxonomical literature at species level. A total abundance of 488 larvae from nine species were collected, 5 (1.02 % in extremely impacted streams, 470 (96.31 % in intermediate streams and 13 (2.66 % in preserved streams. The visual evaluation (HII differed in rela&tion to the water physico-chemical evaluation, in which more variation in the characterization of the sampling sites was observed. In Canonical Correspondence Analysis Simulium subpallidum, S. inscrustatumand S. pertinaxwere significantly associated with intermediate values of most of the variables, and then to intermediate impacted
Full Text Available BACKGROUND: A better understanding of reproductive processes in parasitic nematodes may lead to development of new anthelmintics and control strategies for combating disabling and disfiguring neglected tropical diseases such as lymphatic filariasis and onchocerciasis. Transcriptomatic analysis has provided important new insights into mechanisms of reproduction and development in other invertebrates. We have performed the first genome-wide analysis of gender-associated (GA gene expression in a filarial nematode to improve understanding of key reproductive processes in these parasites. METHODOLOGY/PRINCIPAL FINDINGS: The Version 2 Filarial Microarray with 18,104 elements representing ∼85% of the filarial genome was used to identify GA gene transcripts in adult Brugia malayi worms. Approximately 19% of 14,293 genes were identified as GA genes. Many GA genes have potential Caenorhabditis elegans homologues annotated as germline-, oogenesis-, spermatogenesis-, and early embryogenesis- enriched. The potential C. elegans homologues of the filarial GA genes have a higher frequency of severe RNAi phenotypes (such as lethal and sterility than other C. elegans genes. Molecular functions and biological processes associated with GA genes were gender-segregated. Peptidase, ligase, transferase, regulator activity for kinase and transcription, and rRNA and lipid binding were associated with female GA genes. In contrast, catalytic activity from kinase, ATP, and carbohydrate binding were associated with male GA genes. Cell cycle, transcription, translation, and biological regulation were increased in females, whereas metabolic processes of phosphate and carbohydrate metabolism, energy generation, and cell communication were increased in males. Significantly enriched pathways in females were associated with cell growth and protein synthesis, whereas metabolic pathways such as pentose phosphate and energy production pathways were enriched in males. There were
钱门宝; 陈颖丹; 周晓农
In 2009, the Disease Reference Group on Helminth Infections (DRG4) was established by the Special Programme for Research and Training in Tropical Diseases (TDR) to comprehensively review recent advances, identify gaps and rank priorities in helminthiases research towards control and elimination. Six major human helminthiases are targeted, namely onchocerciasis, lymphatic filariasis, soil-transmitted helminthiases, schistosomiasis, food-borne trematodiasis and cysticercosis/taeniasis. Systematic reports made by the DRG4 from such aspects as the impact of helminthiases, control and elimination, interventions, diagnostics, social-ecology and health systems, modeling, basic research and capacity building in research was published in PLoS Neglected Tropical Diseases in 2012. Generalized introduction is presented here and further analysis of its influence on the research of the major helminthiases in China is done.%2009年,世界卫生组织下属的热带病研究和培训特别规划署(TDR)成立了蠕虫病专家组(DRG4),以总结和评价当前主要蠕虫病(盘尾丝虫病、淋巴丝虫病、土源性蠕虫病、血吸虫病、食源性吸虫病和囊尾蚴病/带绦虫病)的研究现状和不足,以及为达到控制和消除目标所需开展的研究重点.专家组从蠕虫病的影响、控制与消除、干预、诊断、社会生态学及卫生体系、模型、基础研究和研究能力建设等方面作了系统的阐述,并集辑发表在2012年的《科学图书馆——被忽视的热带病》(PLoS Neglected Tropical Diseases)上.本文概括介绍其内容,并简要分析其对中国主要蠕虫病研究的启示.
Roger K Prichard
Full Text Available Recognising the burden helminth infections impose on human populations, and particularly the poor, major intervention programmes have been launched to control onchocerciasis, lymphatic filariasis, soil-transmitted helminthiases, schistosomiasis, and cysticercosis. The Disease Reference Group on Helminth Infections (DRG4, established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR, was given the mandate to review helminthiases research and identify research priorities and gaps. A summary of current helminth control initiatives is presented and available tools are described. Most of these programmes are highly dependent on mass drug administration (MDA of anthelmintic drugs (donated or available at low cost and require annual or biannual treatment of large numbers of at-risk populations, over prolonged periods of time. The continuation of prolonged MDA with a limited number of anthelmintics greatly increases the probability that drug resistance will develop, which would raise serious problems for continuation of control and the achievement of elimination. Most initiatives have focussed on a single type of helminth infection, but recognition of co-endemicity and polyparasitism is leading to more integration of control. An understanding of the implications of control integration for implementation, treatment coverage, combination of pharmaceuticals, and monitoring is needed. To achieve the goals of morbidity reduction or elimination of infection, novel tools need to be developed, including more efficacious drugs, vaccines, and/or antivectorial agents, new diagnostics for infection and assessment of drug efficacy, and markers for possible anthelmintic resistance. In addition, there is a need for the development of new formulations of some existing anthelmintics (e.g., paediatric formulations. To achieve ultimate elimination of helminth parasites, treatments for the above mentioned helminthiases, and for taeniasis
刘丽琴; 孙翔; 谭杰
breast solid nodules in order to provide an new method for early screening of breast cancer. Methods Eighty-four female patients with breast solid nodule ( 105 solid nodules ) who were admitted and treated in our hospital from May 2012 to October 2015 were enrolled in the study.All the patients received conventional ultrasound and ultrasound elasticity imaging examination.Taking the pathological diagnosis results after solid nodulectomy in onchocerciasis as gold standard, the accuracy, sensitivity, specificity, positive and negative predictive value in the diagnosis of breast solid nodule by means of conventional ultrasound scoring, ultrasound elasticity imaging scoring, strain rate ratio, conventional ultrasound combined with ultrasound elasticity imaging scoring were evaluated,moreover, the ROC curve was drawn by SPSS 20.0 software, finally,the results were statistically analyzed.Results The pathological examination results showed that among 105 solid nodules,there were 29 malignant nodules and 76 benign nodules.The accuracy, sensitivity, specificity, positive predictive value, negative predictive value by conventional ultrasound scoring, ultrasound elasticity imaging scoring,strain rate ratio, conventional ultrasound combined with ultrasound elasticity imaging scoring in diagnosis of benign or malignant breast solid nodules were ( 85.71%, 79.31%, 88.15%, 71.875%, 91.78%); ( 82.86%, 72.41%, 86.84%, 67.74%, 89.19%);(84.76%,75.86%,88.16%,70.97%,90.54%);(89.52%,93.10%,88.53%,71.05%,97.01%), respectively.The sensitivity by conventional ultrasound combined with ultrasound elasticity imaging scoring was significantly higher than that by conventional ultrasound scoring, ultrasound elasticity imaging scoring,strain rate ratio,respectively (χ2 =5.221,10.247,6.872, P <0.05).The area under ROC curve by conventional ultrasound scoring, conventional ultrasound combined with ultrasound elasticity imaging scoring,strain rate ratio, ultrasound elasticity imaging scoring was 0