Clinical picture and outcome of Serious Adverse Events in the treatment of Onchocerciasis

Ivermectin (Mectizan®) is the only drug currently recommended for the treatment and control of onchocerciasis. Serious adverse events rarely occur during treatment, except in subjects heavily infected with Loa Loa. This review of drug-related serious adverse events in the treatment of onchocerciasis therefore revisited the pre-Mectizan® reference drugs, DEC and suramin, and other candidate drugs studied extensively for the treatment of human onchocerciasis. The benzimidazole carbamate derivatives and the antibiotic doxycycline were excluded, since no serious adverse events have been reported regarding their use. Using recommended definitions, serious adverse events reported or observed after the use of each drug were summarised, the level of attribution determined, and the results tabulated. Prominence was given to treatment-related deaths. The clinical picture of severe symptomatic postural hypotension is described and used to illustrate the difference between the severity and the seriousness of an adverse event. The epidemiology, management and outcome of serious adverse events are presented. The role of future research is discussed

Entrenching African Pentecostalism in the United States of America: A Study of a Ghanaian Founded Charismatic Church in South Florida

For the past three decades, there has been a rapid growth of African Pentecostal Christianity on America’s Christian religious scene. In general, researchers in Christian mission studies have concluded that the flow of Christian religious currents from Africa and other Third World countries to the West is something of a Christian mission in reverse process. Using agency and invention of tradition as the theoretical leads, this study explores the roles lay immigrants played in the rooting of the Christian Restoration Ministries International (CRMI), a Ghanaian founded charismatic church, in Miami, as a case study of how African Pentecostal churches originate in America. The study also shows how the Christian Restoration Ministries International (CRMI), practices an invented version of Ghanaian Pentecostalism. The study is field-work based. It concludes that the so called reverse mission thrives on the crucial roles of lay African migrant worshipers and their inventiveness

Determinants of Joint Venture Performance: a Study of International Joint Ventures in the United States (Japan, Europe).

This study focuses on: (1) the motivations for international joint venture (IJV) formation in the United States; (2) the bases and outcomes of bargaining between partners; and (3) the relationship between the outcomes of bargaining and joint venture performance. Forty U.S.-based joint ventures formed by U.S. firms with Japanese (22) and European (18) partners were studied. These IJVs operated in the manufacturing sector of the economy. The results of the study show that both U.S. government regulations and/or attitudes (GRA) and business-related factors were significant motivators for IJV formation. However, business-related factors were much stronger motivators than GRA for the whole sample. Further, GRA was a stronger motivational factor for Japanese multinationals (MNCs) than for European (MNCs). The findings also indicated that high relative bargaining power (RBP) led to the use of appropriate partner selection criteria and to high equity ownership in the IJV. However, the level of RBP did not determine the exercise of management control or the level of cooperation between the partners. The results on the determinants of IJV performance revealed that: (1) the level of control exercised significantly impacted IJV performance; (2) the level of cooperation between partners significantly impacted performance; (3) no relationship was found between selection of partner in the same business as the IJV and IJV performance; and (4) no relationship was found between equity ownership and IJV performance. Additionally, there was evidence of differential control over the IJV\u27s functions. Specifically, the U.S. firm, the foreign partner and IJV management generally exercised control over different functional areas. The study has a number of implications for strategy research and practice: (1) it provides an empirical base for explaining the motivations of U.S. firms and foreign MNCs that set up joint ventures in the U.S.; (2) it provides an integrated model that, it is hoped, will guide future research on joint ventures: (3) it provides an empirical case for assessing the performance of joint ventures; and finally, (4) it suggests to those who run joint ventures factors that should receive emphasis in order to enhance joint venture performance

Immunohistological studies on neoplasms of female and male Onchocerca volvulus: filarial origin and absence of Wolbachia from tumor cells

Up to 5% of untreated female Onchocerca volvulus filariae develop potentially fatal pleomorphic neoplasms, whose incidence is increased following ivermectin treatment. We studied the occurrence of 8 filarial proteins and of Wolbachia endobacteria in the tumor cells. Onchocercomas from patients, untreated and treated with antibiotics and anthelminthics, were examined by immunohistology. Neoplasms were diagnosed in 112 of 3587 female and in 2 of 1570 male O. volvulus. The following proteins and other compounds of O. volvulus were expressed in the cells of the neoplasms: glutathione S-transferase 1, lysosomal aspartic protease, cAMP-dependent protein kinase, alpha-enolase, aspartate aminotransferase, ankyrin E1, tropomyosin, heat shock protein 60, transforming growth factor-beta, and prostaglandin E2. These findings prove the filarial origin of the neoplasms and confirm the pleomorphism of the tumor cells. Signs indicating malignancy of the neoplasms are described. Wolbachia were observed in the hypodermis, oocytes, and embryos of tumor-harbouring filariae using antibodies against Wolbachia surface protein, Wolbachia HtrA-type serine protease, and Wolbachia aspartate aminotransferase. In contrast, Wolbachia were not found in the cells of the neoplasms. Further, neoplasm-containing worms were not observed after more than 10 months after the start of sufficient treatment with doxycycline or doxycycline plus ivermectin

Wolbachia endobacteria depletion by doxycycline as antifilarial therapy has macrofilaricidal activity in onchocerciasis: a randomized placebo-controlled study

In a randomized, placebo-controlled trial in Ghana, 67 onchocerciasis patients received 200-mg/day doxycycline for 4–6 weeks, followed by ivermectin (IVM) after 6 months. After 6–27 months, efficacy was evaluated by onchocercoma histology, PCR and microfilariae determination. Administration of doxycycline resulted in endobacteria depletion and female worm sterilization. The 6-week treatment was macrofilaricidal, with >60% of the female worms found dead, despite the presence of new, Wolbachia-containing worms acquired after the administration of doxycycline. Doxycycline may be developed as second-line drug for onchocerciasis, to be administered in areas without transmission, in foci with IVM resistance and in areas with Loa co-infections

The potential impact of moxidectin on onchocerciasis elimination in Africa: an economic evaluation based on the Phase II clinical trial data

BACKGROUND: Spurred by success in several foci, onchocerciasis control policy in Africa has shifted from morbidity control to elimination of infection. Clinical trials have demonstrated that moxidectin is substantially more efficacious than ivermectin in effecting sustained reductions in skin microfilarial load and, therefore, may accelerate progress towards elimination. We compare the potential cost-effectiveness of annual moxidectin with annual and biannual ivermectin treatment. METHODS: Data from the first clinical study of moxidectin were used to parameterise the onchocerciasis transmission model EPIONCHO to investigate, for different epidemiological and programmatic scenarios in African savannah settings, the number of years and in-country costs necessary to reach the operational thresholds for cessation of treatment, comparing annual and biannual ivermectin with annual moxidectin treatment. RESULTS: Annual moxidectin and biannual ivermectin treatment would achieve similar reductions in programme duration relative to annual ivermectin treatment. Unlike biannual ivermectin treatment, annual moxidectin treatment would not incur a considerable increase in programmatic costs and, therefore, would generate sizeable in-country cost savings (assuming the drug is donated). Furthermore, the impact of moxidectin, unlike ivermectin, was not substantively influenced by the timing of treatment relative to seasonal patterns of transmission. CONCLUSIONS: Moxidectin is a promising new drug for the control and elimination of onchocerciasis. It has high programmatic value particularly when resource limitation prevents a biannual treatment strategy, or optimal timing of treatment relative to peak transmission season is not feasible. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-015-0779-4) contains supplementary material, which is available to authorized users

The Pharmacokinetics and Interactions of Ivermectin in Humans—A Mini-review

Ivermectin is an antiparasitic drug with a broad spectrum of activity, high efficacy as well as a wide margin of safety. Since 1987, this compound has a widespread use in veterinary medicine and it use has been extended in humans. Here we present a brief review of the information availabile regarding the pharmacokinetics and interactions of ivermectin in humans. Awareness of these characteristics could improve the clinical efficacy of Ivermectin. All Authors declare that they do not have any Conflict of interest and that the work is original. All Authors agree that the contents of the manuscript are confidential and will not be copyrighted, submitted, or published elsewhere (including the Internet), in any language, while acceptance by the Journal is under consideration

Infection with Mansonella perstans Nematodes in Buruli Ulcer Patients, Ghana.

During August 2010-December 2012, we conducted a study of patients in Ghana who had Buruli ulcer, caused by Mycobacterium ulcerans, and found that 23% were co-infected with Mansonella perstans nematodes; 13% of controls also had M. perstans infection. M. perstans co-infection should be considered in the diagnosis and treatment of Buruli ulcer

The Annotated Genome of Wolbachia from the Filarial Nematode Brugia malayi: What It Means for Progress in Antifilarial Medicine

Filarial nematodes contain endosymbiotic bacteria of the genus Wolbachia. As described in the April 2005 issue of PLoS Biology, Foster et al. have sequenced the genome of the Wolbachia that lives in the nematode Brugia malayi. What are the clinical implications

The Effect of Azithromycin on Ivermectin Pharmacokinetics—A Population Pharmacokinetic Model Analysis

This paper describes the use of a modeling and simulation approach to explore a reported pharmacokinetic interaction between two drugs (ivermectin and azithromycin), which along with albendazole, are being developed for combination use in neglected tropical diseases. This approach is complementary to more traditional pharmacokinetic and safety studies that need to be conducted to support combined use of different health interventions. A mathematical model of ivermectin pharmacokinetics was created and used to simulate multiple trials, and the probability of certain outcomes (very high peak blood ivermectin levels when given in combination) was determined. All simulated peak blood levels were within ranges known to be safe and well tolerated. Additional field studies are needed to confirm these findings