Global elimination of lymphatic filariasis
Authors: Martial L Ndeffo-Mbah, Alison P Galvani
Journal: The Lancet Infectious Diseases (2016)

Lymphatic filariasis is one of the most debilitating neglected tropical diseases, the clinical manifestations of which include painful and incapacitating lymphoedema.1Ramaiah KD Ottesen EA Progress and impact of 13 years of the global programme to eliminate lymphatic filariasis on reducing the burden of filarial disease.PLoS Negl Trop Dis. 2014; 8: e3319Crossref PubMed Scopus (187) Google Scholar Among the estimated 68 million people infected, 36 million are microfilaria carriers and 40 million are symptomatic.1Ramaiah KD Ottesen EA Progress and impact of 13 years of the global programme to eliminate lymphatic filariasis on reducing the burden of filarial disease.PLoS Negl Trop Dis. 2014; 8: e3319Crossref PubMed Scopus (187) Google Scholar Additionally, 946 million people live in areas of southeast Asia and sub-Saharan Africa where mosquito-borne filariasis is endemic and are, therefore, at risk of infection.1Ramaiah KD Ottesen EA Progress and impact of 13 years of the global programme to eliminate lymphatic filariasis on reducing the burden of filarial disease.PLoS Negl Trop Dis. 2014; 8: e3319Crossref PubMed Scopus (187) Google Scholar In 2000, WHO launched the Global Programme to Eliminate Lymphatic Filariasis (GPELF), which aims to interrupt transmission of lymphatic filariasis by 2020.2Rebollo MP Bockarie MJ Toward the elimination of lymphatic filariasis by 2020: treatment update and impact assessment for the endgame.Expert Rev Anti Infect Ther. 2013; 11: 723-731Crossref PubMed Scopus (51) Google Scholar To achieve this elimination goal, GPELF recommends annual mass drug administration at a minimum population coverage of 65%.3Taylor MJ Hoerauf A Bockarie M Lymphatic filariasis and onchocerciasis.Lancet. 2010; 376: 1175-1185Summary Full Text Full Text PDF PubMed Scopus (457) Google Scholar, 4WHOWorld Health Organization Global Programme to Eliminate Lymphatic Filariasis: progress report 2000–2009 and strategic plan 2010–2020.http://www.searo.who.int/entity/vector_borne_tropical_diseases/topics/lymphatic_filariasis/LFREP.pdfDate: 2010Google Scholar The double-drug regimens currently administered are a combination of albendazole with either ivermectin or diethylcarbamazine. In view of adverse effects of diethylcarbamazine for individuals co-infected with onchocerciasis, the ivermectin and albendazole combination is recommended in areas co-endemic with onchocerciasis. These double-drug treatments mainly clear microfilariae that cause transmission but with less effect on adult filariasis worms.5Thomsen EK Sanuku N Baea M et al.Efficacy, safety, and pharmacokinetics of coadministered diethylcarbamazine, albendazole, and ivermectin for treatment of bancroftian filariasis.Clin Infect Dis. 2016; 62: 334-341Crossref PubMed Scopus (118) Google Scholar By contrast, findings of a small clinical trial suggested that a triple-drug regimen combining ivermectin, diethylcarbamazine, and albendazole was much more effective at clearing both microfilariae and adult worms.5Thomsen EK Sanuku N Baea M et al.Efficacy, safety, and pharmacokinetics of coadministered diethylcarbamazine, albendazole, and ivermectin for treatment of bancroftian filariasis.Clin Infect Dis. 2016; 62: 334-341Crossref PubMed Scopus (118) Google Scholar As a result, shifting from double-drug to triple-drug therapy could have the potential to accelerate progress towards elimination goals substantially, with the exception of communities within west and central Africa where onchocerciasis and loiasis are endemic, due to adverse effects with ivermectin and diethylcarbamazine, respectively.3Taylor MJ Hoerauf A Bockarie M Lymphatic filariasis and onchocerciasis.Lancet. 2010; 376: 1175-1185Summary Full Text Full Text PDF PubMed Scopus (457) Google Scholar, 6Zouré HGM Noma M Tekle AH et al.The geographic distribution of onchocerciasis in the 20 participating countries of the African Programme for Onchocerciasis Control: (2) pre-control endemicity levels and estimated number infected.Parasit Vectors. 2014; 7: 326Crossref PubMed Scopus (94) Google Scholar, 7Zouré HGM Wanji S Noma M et al.The geographic distribution of Loa loa in Africa: results of large-scale implementation of the Rapid Assessment Procedure for Loiasis (RAPLOA).PLoS Negl Trop Dis. 2011; 5: e1210Crossref PubMed Scopus (180) Google Scholar In The Lancet Infectious Diseases, Michael Irvine and colleagues conduct elegant analyses based on a series of mathematical models to translate the individual-level clinical trial results to population-level effectiveness of the triple-drug regimen.8Irvine MA Stolk WA Smith ME et al.Effectiveness of a triple-drug regimen for global elimination of lymphatic filariasis: a modelling study.Lancet Infect Dis. 2016; (published online Dec 21.)http://dx.doi.org/10.1016/S1473-3099(16)30467-4PubMed Google Scholar They further apply their findings to ascertain the extent to which the triple-drug regimen could improve the likelihood of interrupting transmission of lymphatic filariasis. Specifically, they show that annual mass drug administration of the triple-drug combination might accelerate elimination of lymphatic filariasis by 1–2 years in areas of low prevalence and by 4–5 years in areas of moderate and high prevalence. Furthermore, Irvine and colleagues show that expanding coverage of mass drug administration beyond 75% will be essential for meeting WHO's elimination goals, particularly in high-prevalence areas.8Irvine MA Stolk WA Smith ME et al.Effectiveness of a triple-drug regimen for global elimination of lymphatic filariasis: a modelling study.Lancet Infect Dis. 2016; (published online Dec 21.)http://dx.doi.org/10.1016/S1473-3099(16)30467-4PubMed Google Scholar These results highlight the necessity of tailoring optimum control strategies to specific settings. Furthermore, the assessments are informative to the design of endgame strategies and might prove instrumental to policy decisions underlying elimination of lymphatic filariasis. Although improving the effectiveness of treatment regimens will undoubtedly facilitate the attainment of GPELF goals, it is important to concomitantly address logistical challenges that have restricted the coverage of mass drug administration in target countries. Between 2000 and 2012, GPELF provided more than 4·5 billion treatments in 59 countries, which has reduced global prevalence of lymphatic filariasis by 59%, microfilaraemia prevalence by 68%, hydrocele prevalence by 50%, and lymphoedema prevalence by 25%.1Ramaiah KD Ottesen EA Progress and impact of 13 years of the global programme to eliminate lymphatic filariasis on reducing the burden of filarial disease.PLoS Negl Trop Dis. 2014; 8: e3319Crossref PubMed Scopus (187) Google Scholar Underlying these global averages is considerable heterogeneity among affected countries. Specifically, eight of 59 countries have declared elimination of lymphatic filariasis, 12 have entered the phase after mass drug administration surveillance, 13 have implemented the recommended coverage, 16 have not yet reached recommended coverage, and ten have not yet initiated mass drug administration.9WHOGlobal Programme to Eliminate Lymphatic Filariasis: progress report, 2015.Wkly Epidemiol Rec. 2016; 39: 441-460Google Scholar, 10Rebollo MP Bockarie MJ Can lymphatic filariasis be eliminated by 2020?.Trends Parasitol. 2016; (published online Oct 17.)https://doi.org/10.1016/j.pt.2016.09.009Summary Full Text Full Text PDF PubMed Scopus (20) Google Scholar Thus, altogether, around half of affected countries have not yet implemented GPELF recommendations. Civil unrest (eg, in South Sudan), the Ebola virus disease outbreak in Liberia, Sierra Leone and Guinea, and non-compliance to treatment are just some of the myriad factors that complicate programme implementation.9WHOGlobal Programme to Eliminate Lymphatic Filariasis: progress report, 2015.Wkly Epidemiol Rec. 2016; 39: 441-460Google Scholar A principal consideration for the optimisation of elimination strategies, particularly in resource-constrained settings, is the cost-effectiveness of innovative interventions that integrate new diagnostic methods and treatment of lymphatic filariasis in the context of economic constraints and logistical barriers. Since drugs for the lymphatic filariasis programme are donated by manufacturers,11Kastner RJ Stone CM Steinmann P Tanner M Tediosi F What is needed to eradicate lymphatic filariasis? A model-based assessment on the impact of scaling up mass drug administration programs.PLoS Negl Trop Dis. 2015; 9: e0004147Crossref Scopus (23) Google Scholar and scale-up and geographical expansion of mass drug administration are cost-effective for eradication of lymphatic filariasis,12Stone CM Kastner R Steinmann P Chitnis N Tanner M Tediosi F Modelling the health impact and cost-effectiveness of lymphatic filariasis eradication under varying levels of mass drug administration scale-up and geographic coverage.BMJ Glob Health. 2016; 1: e000021Crossref Scopus (14) Google Scholar we anticipate that the marginal benefits of the triple-drug regimen as a replacement for double-drug treatment would further improve the cost-effectiveness of mass drug administration strategies. With only 4 years remaining before the 2020 target, rapid scale-up of mass drug administration and prompt decisions about the implementation of alternative strategies, such as biannual mass drug administration and triple-drug therapy, are imperative to interrupting lymphatic filariasis transmission in all countries. We declare no competing interests. Effectiveness of a triple-drug regimen for global elimination of lymphatic filariasis: a modelling studySimulation modelling suggests that the triple-drug regimen has potential to accelerate the elimination of lymphatic filariasis if high population coverage of mass drug administration can be achieved and if systematic non-adherence with mass drug administration is low. Future work will reassess these estimates in light of more clinical trial data and to understand the effect on an individual country's programme. Full-Text PDF Open Access