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      Analysis of severe adverse effects following community-based ivermectin treatment in the Democratic Republic of Congo

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          Abstract

          Background

          The progress of mass, community-directed, treatment with ivermectin (CDTI) for onchocerciasis control was disrupted by severe adverse effects (SAE) in the Democratic Republic of Congo (DRC). The study aimed at determining the frequency of post-CDTI SAE as well as factors associated with the occurrence of SAE.

          Methods

          Our retrospective study relied on SAE collection cards, as archived by the DRC Ministry of Health, and compiled for people who benefited from ivermectin treatment then further developed SAE. The study included 945 post-CDTI SAE recorded in DRC between 2003 and 2017. These cases occurred in 15 projects out of 22 projects implemented in the country. All cards were reviewed and analysed.

          Results

          Between the years 2003 and 2017, the total average population treated was around 15,552,588 among which 945 cases of SAE were registered in DR Congo, i.e. 6 cases of SAE for 100,000 persons treated per year. 55 deaths related to post-CDTI SAE were recorded, which represents 5.8% of all cases of SAE. Non-neurological SAE were dominated by severe headaches (74.8%), myalgia (64.0%) and arthralgia (62.7%). Neurological SAE were mainly coma (94.1%), motor deficit (75.4%) and palpebral subconjunctival haemorrhages (38.8%). Factors associated with the occurrence of SAE were: male, age over 18 years old, alcohol consumption, hemp intake and the presence of loiasis. The study also highlighted weaknesses of the National Program for Onchocerciasis Control (NPOC)  in terms of awareness campaigns among the population.

          Conclusion

          Co-endemicity of loiasis and onchocerciasis is one of the key factors responsible for the occurrence of SAE following ivermectin treatment. Mobilization of resources necessary to the appropriate management of SAE and awareness of populations are essential to achieve onchocerciasis control in DRC.

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          Most cited references37

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          River Blindness: A Success Story under Threat?

          The success of the Onchocerciasis Control Programme is undeniable and exemplary, say the authors, but it is too early to claim victory against river blindness.
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            “Test and not treat” for onchocerciasis control in a Loa loa endemic area

            Background Implementation of ivermectin-based community treatment for onchocerciasis or lymphatic filariasis elimination has been delayed in Central Africa because of severe adverse events (SAEs), including death, in people with high levels of circulating Loa loa microfilariae (mf). LoaScope, a rapid field-friendly diagnostic tool to quantify L. loa mf in peripheral blood, permits point-of-care identification of individuals “at risk” for SAEs. Methods A “Test and not Treat” (TaNT) strategy was used to implement ivermectin treatment in the Okola health district in Cameroon, where ivermectin distribution was halted in 1999 after the occurrence of fatal Loa-related SAEs. The LoaScope was used to identify and exclude individuals with >20,000 mf per milliliter of blood (at-risk for SAEs) from ivermectin treatment. Active surveillance for post-treatment adverse events (AEs) was conducted daily for 7 days. Results Between August and October 2015, 16,259 (71.1%) individuals >=5 years of age were tested out of a target population of ~22,800. Among the ivermectin-eligible population, 15,522 (95.5%) received ivermectin; 340 (2.1%) were excluded from ivermectin treatment because of a L. loa density above the risk-threshold and 397 (2.4%) were excluded for pregnancy or illness. No SAEs were observed. Non-severe AEs were recorded in 934 individuals, most (67%) of whom had no detectable L. loa mf. Conclusions The LoaScope-based TaNT strategy permitted safe re-implementation of community-wide ivermectin distribution in a heretofore ‘off limits’ health district in Cameroon and is an extremely promising and practical approach for large-scale ivermectin treatment for lymphatic filariasis and onchocerciasis elimination in Loa loa-endemic areas.
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              The therapeutic potential of cannabis and cannabinoids.

              Cannabis-based medications have been a topic of intense study since the endogenous cannabinoid system was discovered two decades ago. In 2011, for the first time, a cannabis extract was approved for clinical use in Germany. Selective literature review. Cannabis-based medications exert their effects mainly through the activation of cannabinoid receptors (CB1 and CB2). More than 100 controlled clinical trials of cannabinoids or whole-plant preparations for various indications have been conducted since 1975. The findings of these trials have led to the approval of cannabis-based medicines (dronabinol, nabilone, and a cannabis extract [THC:CBD=1:1]) in several countries. In Germany, a cannabis extract was approved in 2011 for the treatment of moderate to severe refractory spasticity in multiple sclerosis. It is commonly used off label for the treatment of anorexia, nausea, and neuropathic pain. Patients can also apply for government permission to buy medicinal cannabis flowers for self-treatment under medical supervision. The most common side effects of cannabinoids are tiredness and dizziness (in more than 10% of patients), psychological effects, and dry mouth. Tolerance to these side effects nearly always develops within a short time. Withdrawal symptoms are hardly ever a problem in the therapeutic setting. There is now clear evidence that cannabinoids are useful for the treatment of various medical conditions.
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                Author and article information

                Contributors
                0032 493 93 96 35 , jcmakebof@yahoo.fr
                danielmuteba2002@yahoo.fr
                pmansiangi@gmail.com
                feilunga@yahoo.fr
                yves.coppieters@ulb.be
                Journal
                BMC Pharmacol Toxicol
                BMC Pharmacol Toxicol
                BMC Pharmacology & Toxicology
                BioMed Central (London )
                2050-6511
                16 August 2019
                16 August 2019
                2019
                : 20
                : 49
                Affiliations
                [1 ]ISNI 0000 0001 2348 0746, GRID grid.4989.c, School of Public Health, Université Libre de Bruxelles (ULB), ; Route de Lennik numéro 808 à 1070, Brussels, Belgium
                [2 ]National Program for Onchocerciasis Control (NPOC), Kinshasa, Gombe Democratic Republic of Congo
                [3 ]ISNI 0000 0000 9927 0991, GRID grid.9783.5, School of Public Health, Faculty of Medicine, Université de Kinshasa (UNIKIN), ; Route de Kimwenza, Lemba Kinshasa, Democratic Republic of Congo
                [4 ]GRID grid.442324.7, Institut Supérieur des Techniques Médicales (ISTM), ; Route de Kimwenza, Lemba Kinshasa, Democratic Republic of Congo
                Article
                327
                10.1186/s40360-019-0327-5
                6697993
                31420005
                b3781808-c6bf-4b62-827f-1e80a7279bae
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 28 November 2018
                : 23 July 2019
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                Toxicology
                onchocerciasis,ivermectin,severe adverse effects,communities,community-directed treatment with ivermectin,democratic republic of congo

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