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      Excess Mortality Associated With Loiasis: Confirmation by a New Retrospective Cohort Study Conducted in the Republic of Congo

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          Abstract

          Background

          Loiasis ( Loa loa filariasis) is considered a benign disease and is currently not included in the World Health Organization’s (WHO's) list of Neglected Tropical Diseases, despite mounting evidence suggesting significant disease burden in endemic areas. We conducted a retrospective cohort study to assess the mortality associated with L. loa microfilaremia in the Southwestern Republic of Congo.

          Methods

          The cohort included 3329 individuals from 53 villages screened for loiasis in 2004. We compared mortality rates in 2021 for individuals initially diagnosed as with or without L. loa microfilariae 17 years earlier. Data were analyzed at the community level to calculate crude mortality rates. Survival models were used to estimate the effect of L. loa microfilaremia on mortality in the population.

          Results

          At baseline, prevalence of microfilaremia was 16.2%. During 17.62 years of cohort follow-up, 751 deaths were recorded, representing a crude mortality rate of 15.36 (95% CI, 14.28–16.50) per 1000 person-years. Median survival time was 58.5 (95% CI, 49.7–67.3) years and 39.2 (95% CI, 32.6–45.8) years for amicrofilaremic and microfilaremic indiviudals, respectively.

          Conclusions

          A significant reduction in life expectancy was associated with L. loa microfilaremia, confirming previous observations from Cameroon. This adds to the evidence that loiasis is not a benign disease and deserves to be included in the WHO's list of Neglected Tropical Diseases.

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          Serious reactions after mass treatment of onchocerciasis with ivermectin in an area endemic for Loa loa infection.

          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 onchocerciasis control in areas where loiasis is endemic. In communities at risk, monitoring procedures should be established and adhered to during CBIT so that people developing serious reactions may receive appropriate treatment.
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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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              Loiasis.

              Loiasis affects millions of individuals living in the forest and savannah regions of Central Africa. In some areas, this disease constitutes one of the most common reasons for medical consultation. The burden posed by loiasis is probably under-estimated and, in addition, individuals harbouring high Loa microfilarial loads are at risk of developing serious neurological reactions after treatment with diethylcarbamazine or ivermectin. These events are currently significantly hampering the development of the African Programme for Onchocerciasis Control, and operational research is required to address the issue. The results of recent studies, involving either human populations from endemic areas or monkey models, have provided much more detail of the mechanisms associated with amicrofilaraemic or so-called 'occult' loiasis. New diagnostic tools have also been developed in the last decade, and various protocols are now available for the risk-free treatment of loiasis cases.
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                Author and article information

                Contributors
                Journal
                Open Forum Infect Dis
                Open Forum Infect Dis
                ofid
                Open Forum Infectious Diseases
                Oxford University Press (US )
                2328-8957
                March 2023
                24 February 2023
                24 February 2023
                : 10
                : 3
                : ofad103
                Affiliations
                UMI 233 TransVIHMI, Université de Montpellier, Institut de Recherche pour le Développement (IRD), INSERM Unité , Montpellier, France
                Programme National de Lutte contre l'Onchocercose, Direction de l'Épidémiologie et de la Lutte contre les Maladies, Ministère de la Santé et de la Population , Brazzaville, République du Congo
                MRC Centre for Global Infectious Disease Analysis, Jameel Institute for Disease and Emergency Analytics, Imperial College London , London, United Kingdom
                UMI 233 TransVIHMI, Université de Montpellier, Institut de Recherche pour le Développement (IRD), INSERM Unité , Montpellier, France
                UMI 233 TransVIHMI, Université de Montpellier, Institut de Recherche pour le Développement (IRD), INSERM Unité , Montpellier, France
                Programme National de Lutte contre l'Onchocercose, Direction de l'Épidémiologie et de la Lutte contre les Maladies, Ministère de la Santé et de la Population , Brazzaville, République du Congo
                MRC Centre for Global Infectious Disease Analysis, Jameel Institute for Disease and Emergency Analytics, Imperial College London , London, United Kingdom
                Programme National de Lutte contre l'Onchocercose, Direction de l'Épidémiologie et de la Lutte contre les Maladies, Ministère de la Santé et de la Population , Brazzaville, République du Congo
                Faculté des Sciences de la Santé, Université Marien-Ngouabi , Brazzaville, République du Congo
                Faculté des Sciences de la Santé, Université Marien-Ngouabi , Brazzaville, République du Congo
                UMI 233 TransVIHMI, Université de Montpellier, Institut de Recherche pour le Développement (IRD), INSERM Unité , Montpellier, France
                UMI 233 TransVIHMI, Université de Montpellier, Institut de Recherche pour le Développement (IRD), INSERM Unité , Montpellier, France
                Author notes

                Michel Boussinesq and Cédric B Chesnais equal contribution

                Correspondence: Cédric B. Chesnais, MD, PhD, Institut de Recherche pour le Développement (IRD), INSERM Unité 1175, 911 avenue Agropolis 34000, Montpellier, France ( cedric.chesnais@ 123456ird.fr ).

                Potential conflicts of interest. All authors: no reported conflicts.

                Author information
                https://orcid.org/0000-0002-4400-5204
                https://orcid.org/0000-0002-8779-977X
                Article
                ofad103
                10.1093/ofid/ofad103
                10034755
                36968967
                8876dda9-7ea5-45ad-a2bf-a0f572408fa5
                © The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 December 2022
                : 21 February 2023
                : 23 February 2023
                : 23 March 2023
                Page count
                Pages: 8
                Funding
                Funded by: European Research Council, doi 10.13039/501100000781;
                Award ID: 949963
                Funded by: Sir Henry Wellcome Postdoctoral Fellowship;
                Award ID: 224190/Z/21/Z)
                Funded by: Wellcome Trust, doi 10.13039/100004440;
                Award ID: 224190/Z/21/Z
                Categories
                Major Article
                AcademicSubjects/MED00290

                loiasis,republic of congo,cohort study,filariasis,mortality
                loiasis, republic of congo, cohort study, filariasis, mortality

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