Case definitions for onchocerciasis-associated epilepsy and nodding syndrome: A focused review.

Onchocerciasis-associated epilepsy (OAE) is an important but neglected public health problem in onchocerciasis-endemic areas with insufficient or inadequate onchocerciasis control. Hence, there is a need for an internationally accepted, easy-to-use epidemiological case definition of OAE to identify areas of high Onchocerca volvulus transmission and disease burden requiring treatment and prevention interventions. By including OAE as a manifestation of onchocerciasis, we will considerably improve the accuracy of the overall onchocerciasis disease burden, which is currently underestimated. Hopefully, this will lead to increased interest and funding for onchocerciasis research and control interventions, notably the implementation of more effective elimination measures and treatment and support for affected individuals and their families.

Elimination of human onchocerciasis: progress report, 2021

This progress report provides an update on the progress made towards eliminating nnchocerciasis (river blindness) by the World Health Organization (WHO) as part of its road map on neglected tropical diseases for 2021-2030. The report highlights that the goal is to eliminate the need for mass drug administration of ivermectin in at least one focus in 34 countries by 2030, in more than 50% of the population in at least 16 countries and in the entire endemic population in at least 12 countries. However, challenges remain in achieving these goals, including incomplete mapping of all transmission zones, co-endemicity of onchocerciasis and loiasis, a potential decrease in sensitivity to ivermectin, uncoordinated cross-border work, suboptimal programme implementation and inadequate technical and financial resources. COVID-19 has also delayed national programmes, with millions of doses of preventive chemotherapy that should have been distributed expiring. The report also provides regional highlights, including that in 2021, 23 countries reported having treated a total of 142.3 million people for onchocerciasis, representing 58.1% of global coverage, and that the African region faces the greatest challenge with 99% of the global burden of the disease in this region.

Is the antiparasitic drug ivermectin a suitable candidate for the treatment of epilepsy?

There are only a few drugs that can seriously lay claim to the title of "wonder drug," and ivermectin, the world's first endectocide and forerunner of a completely new class of antiparasitic agents, is among them. Ivermectin, a mixture of two macrolytic lactone derivatives (avermectin B1a and B1b in a ratio of 80:20), exerts its highly potent antiparasitic effect by activating the glutamate-gated chloride channel, which is absent in vertebrate species. However, in mammals, ivermectin activates several other Cys-loop receptors, including the inhibitory γ-aminobutyric acid type A and glycine receptors and the excitatory nicotinic acetylcholine receptor of brain neurons. Based on these effects on vertebrate receptors, ivermectin has recently been proposed to constitute a multifaceted wonder drug for various novel neurological indications, including alcohol use disorders, motor neuron diseases, and epilepsy. This review critically discusses the preclinical and clinical evidence of antiseizure effects of ivermectin and provides several arguments supporting that ivermectin is not a suitable candidate drug for the treatment of epilepsy. First, ivermectin penetrates the mammalian brain poorly, so it does not exert any pharmacological effects via mammalian ligand-gated ion channels in the brain unless it is used at high, potentially toxic doses or the blood-brain barrier is functionally impaired. Second, ivermectin is not selective but activates numerous inhibitory and excitatory receptors. Third, the preclinical evidence for antiseizure effects of ivermectin is equivocal, and at least in part, median effective doses in seizure models are in the range of the median lethal dose. Fourth, the only robust clinical evidence of antiseizure effects stems from the treatment of patients with onchocerciasis, in which the reduction of seizures is due to a reduction in microfilaria densities but not a direct antiseizure effect of ivermectin. We hope that this critical analysis of available data will avert the unjustified hype associated with the recent use of ivermectin to control COVID-19 from recurring in neurological diseases such as epilepsy.

Summary of the 31st meeting of the international task force for disease eradication, 20-21 October 2020

This article provides a brief overview of the 31st meeting of the International TaskForce for Disease Eradication (ITFDE) that was convened at The Carter Center in Atlanta, GA, USA on 20-21 October 2020 to discuss "The impact of the COVID-19 pandemic on eradication and elimination programmes and the way forward." It highlights the results of 7 eradication programmes, with specific conclusions and recommendations for each: Guinea Worm Eradication Programme(dracunculiasis;GWEP);Global Polio Eradication Initiative (GPEI);elimination programmes for measles and rubella (MR), malaria, river blindness (onchocerciasis;RB), and lymphatic filariasis (LF);and the program for the Global Elimination of Trachoma.

Progress in eliminating onchocerciasis in the WHO region of the Americas: disruption of ivermectin mass drug administration in the Yanomami focus area due to the COVID-19 pandemic

This article describes how the COVID-19 pandemic significantly reduced provision of treatment in the Yanomami focus area (YFA) in 2020, especially in the Bolivarian Republic of Venezuela. The distribution of ivermectin for mass treatment (MDA) to prevent onchocerciasis was affected worldwide by the COVID-19 pandemic in 2020, as were MDA programs for other neglected tropical diseases (NTDs). On 1 April 2020, WHO recommended that mass treatment campaigns, active case-finding, and population-based surveys for NTDs be postponed until further notice to reduce the risk of COVID-19 transmission associated with large-scale community health interventions. The Carter Center, which provides major funding to MDA in the Bolivarian Republic of Venezuela, temporarily halted its activities in 2020 due to an administrative problem and, once the COVID-19 pandemic had taken hold, in order to adhere to WHO recommendations, its own policies, and the policies of other donor organizations. Ivermectin treatment continued to be offered in Brazil, supported by the government, with essential health services such as vaccination and malaria control. On 27 July 2021, WHO released new interim guidance for NTD programs. This included a risk-benefit analysis to figure out if activities could be resumed safely and detailed standards for reducing risk with all known precautions (such as wearing masks, socialdistance, hand sanitizing and/or handwashing, limiting live meetings and group size). The program in the Bolivarian Republic of Venezuela followed these instructions and made a plan to get back to work safely, which was what WHO wanted.

Elimination of human onchocerciasis: progress report, 2020

In this report, four countries (Colombia, Ecuador, Guatemala, and Mexico) have completed the WHO-recommended process for verification of the interruption of human onchocerciasis transmission, and many others have ceased mass drug administration (MDA), completed post-treatment surveillance (PTS), or both in at least one transmission area on their territory. Interruption of transmission enabled governments to preserve the benefits acquired over many years of effective MDA with Ivermectin and to discontinue MDA permanently, thereby protecting populations living in endemic areas from morbidity and infection. The eradication of human onchocerciasis would contribute significantly to achieving Sustainable Development Goal (SDG) 3.3, which calls for the eradication of neglected tropical diseases (NTDs) by 2030. All countries endemic for onchocerciasis have reported instances of COVID-19. The impact of the pandemic on NTD interventions has been discussed elsewhere. In many countries, scheduled MDA rounds were postponed due to efforts to prevent the spread of SARS-CoV-2 in onchocerciasis-endemic nations. In 2020, 26.9% fewer patients were treated for onchocerciasis than in 2019. MDA was implemented in fewer nations and implementation units in 2020 (1096 versus 1538 in 2019), resulting in a 27.7% decrease in global geographical coverage. The WHO Global Health Observatory provides access to data submitted by governments.

Community-based trial assessing the impact of annual versus semiannual mass drug administration with ivermectin plus albendazole and praziquantel on helminth infections in northwestern Liberia.

We assessed the impact of three annual vs five semiannual rounds of mass drug administration (MDA) with ivermectin plus albendazole followed by praziquantel for the control or elimination of lymphatic filariasis (LF), onchocerciasis, soil-transmitted helminth (STH) infections and schistosomiasis in Lofa County, Liberia. The study started in 2012 and was interrupted in 2014 during the Ebola virus outbreak. Repeated cross-sectional surveys were conducted in individuals 5 years and older to measure infection markers. Wuchereria bancrofti antigenemia prevalences decreased from 12.5 to 1.2% (90% reduction) and from 13.6 to 4.2% (69% reduction) one year after three rounds of annual or five rounds of semiannual MDA, respectively. Mixed effects logistic regression models showed decreases in odds of antigenemia positivity were 91 and 74% at that time in the annual and semiannual treatment zones, respectively (p < 0.001). Semiannual MDA was slightly more effective for reducing Onchocerca volvulus microfiladermia prevalence and at follow-up 3 were 74% (from 14.4 to 3.7%) and 83% (from 23.6 to 4.5%) in the annual and semiannual treatment zones, respectively. Both treatment schedules had similar beneficial effects on hookworm prevalence. Thus, annual and semiannual MDA with ivermectin and albendazole had similar beneficial impacts on LF, onchocerciasis, and STH in this setting. In contrast, MDA with praziquantel had little impact on hyperendemic Schistosoma mansoni in the study area. Results from a long-term follow-up survey showed that improvements in infection parameters were sustained by routine annual MDA provided by the Liberian Ministry of Health after our study endpoint.

Historical Review and Cost-Effectiveness Assessment of the Programs to Eliminate Onchocerciasis and Trachoma in Mexico.

We present a historical review of two neglected tropical diseases (NTD), namely, onchocerciasis and trachoma, both which were successfully eliminated in Mexico. In addition, we present a cost-effectiveness assessment (CEA) demonstrating that these were worthwhile health interventions. Historically, an estimate of $310.68 and $38.92 per person were spent during the period of time the onchocerciasis and trachoma elimination programs operated, respectively.

Current Use of Ivermectin in Dermatology, Tropical Medicine, and COVID-19: An Update on Pharmacology, Uses, Proven and Varied Proposed Mechanistic Action.

Ivermectin is a broad-spectrum antiparasitic drug with anti-inflammatory, anti-viral, anti-bacterial, and anti-tumor effects. In this review, we discuss the history, pharmacology, multimodal actions, indications in dermatology and tropical medicine, therapeutic and prophylactic use of ivermectin in COVID-19, safety, adverse effects, special considerations, and drug interactions of ivermectin.

What does the COVID-19 pandemic mean for the next decade of onchocerciasis control and elimination?

BACKGROUND: Mass drug administration (MDA) of ivermectin for onchocerciasis has been disrupted by the coronavirus disease 2019 (COVID-19) pandemic. Mathematical modelling can help predict how missed/delayed MDA will affect short-term epidemiological trends and elimination prospects by 2030. METHODS: Two onchocerciasis transmission models (EPIONCHO-IBM and ONCHOSIM) are used to simulate microfilarial prevalence trends, elimination probabilities and age profiles of Onchocerca volvulus microfilarial prevalence and intensity for different treatment histories and transmission settings, assuming no interruption, a 1-y (2020) interruption or a 2-y (2020-2021) interruption. Biannual MDA or increased coverage upon MDA resumption are investigated as remedial strategies. RESULTS: Programmes with shorter MDA histories and settings with high pre-intervention endemicity will be the most affected. Biannual MDA is more effective than increasing coverage for mitigating COVID-19's impact on MDA. Programmes that had already switched to biannual MDA should be minimally affected. In high-transmission settings with short treatment history, a 2-y interruption could lead to increased microfilarial load in children (EPIONCHO-IBM) and adults (ONCHOSIM). CONCLUSIONS: Programmes with shorter (annual MDA) treatment histories should be prioritised for remedial biannual MDA. Increases in microfilarial load could have short- and long-term morbidity and mortality repercussions. These results can guide decision-making to mitigate the impact of COVID-19 on onchocerciasis elimination.

COVID-19: The Ivermectin African Enigma.

INTRODUCTION: The low frequency of cases and deaths from the SARS-CoV-2 COVID-19 virus in some countries of Africa has called our attention about the unusual behavior of this disease. The ivermectin is considered a drug of choice for various parasitic and viral diseases and shown to have in vitro effects against SARS-CoV-2. AIMS: Our study aimed to describe SARS-CoV2 infection and death rates in African countries that participated in an intensive Ivermectin mass campaign carried out to control onchocerciasis and compare them with those of countries that did not participate. METHODS: Data from 19 countries that participated in the World Health Organization (WHO) sponsored African Programme for Onchocerciasis Control (APOC), from 1995 until 2015, were compared with thirty-five (Non-APOC), countries that were not included. Information was obtained from https://www.worldometers.info/coronavirus/ database. Generalized Poisson regression models were used to obtain estimates of the effect of APOC status on cumulative SARS-CoV-2 infection and mortality rates. RESULTS: After controlling for different factors, including the Human Development Index (HDI), APOC countries (vs. non-APOC), show 28% lower mortality (0.72; 95% CI: 0.67-0.78) and 8% lower rate of infection (0.92; 95% CI: 0.91-0.93) due to COVID-19. CONCLUSIONS: The incidence in mortality rates and number of cases is significantly lower among the APOC countries compared to non-APOC countries. That a mass public health preventive campaign against COVID-19 may have taken place, inadvertently, in some African countries with massive community ivermectin use is an attractive hypothesis. Additional studies are needed to confirm it.

INTRODUCCIÓN: La baja frecuencia de casos y muertes por el virus SARS-CoV-2 COVID-19 en algunos países de África llamó nuestra atención sobre el comportamiento inusual de esta enfermedad. La ivermectina se considera un fármaco de elección para diversas enfermedades parasitarias y virales, y se ha demostrado que tiene efectos in vitro contra el SARS-CoV-2. OBJETIVOS: Nuestro estudio tiene el objetivo describir las tasas de infección y mortalidad del SARS-CoV-2 en los países africanos que participaron en una campaña intensiva masiva de ivermectina para el control de la oncocercosis y compararlas con las de los países que no participaron. MÉTODOS: Los datos de 19 países que participaron en el Programa Africano para el Control de la Oncocercosis (APOC) patrocinado por la Organización Mundial de la Salud (OMS), desde 1995 hasta 2015, se compararon con 35 países que no fueron incluidos (NO APOC). La información sobre casos y muertes por COVID-19 se obtuvo de la base de datos https://www.worldometers.info/coronavirus/. Se utilizaron modelos de regresión de Poisson para obtener estimaciones del efecto del estado APOC sobre las tasas acumuladas de infección y mortalidad por SARS-CoV-2. RESULTADOS: Después de controlar diferentes factores, incluido el Índice de Desarrollo Humano (IDH), los países APOC (frente a los no APOC) mostraron una mortalidad 28% menor (razón de tasas ajustada: RR= 0.72, IC 95%: 0.67-0.78) y una tasa de infección 8% menor (RR= 0.92, IC 95%: 0.91-0.93) por COVID-19. CONCLUSIONES: Las tasas de mortalidad e infección son significativamente más bajas en países APOC en comparación con los países no APOC. Una campaña preventiva masiva de salud pública contra el COVID-19 pudo haber tenido lugar inadvertidamente en algunos países africanos con un uso masivo de ivermectina en la comunidad es una hipótesis atractiva. Se necesitan estudios adicionales para confirmarlo.