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Pharmaceutics Jan 2024Onchocerciasis treatment and control relies mainly on the use of ivermectin which has high activity against the microfilarial stage of but limited activity against the...
Onchocerciasis treatment and control relies mainly on the use of ivermectin which has high activity against the microfilarial stage of but limited activity against the long-lived, tissue dwelling adult nematodes. As this neglected tropical disease has now been targeted for elimination, there is an urgent need for new drugs to combat these parasites, ideally with macrofilaricidal activity. In this study, we have examined the anti- activity of a range of existing FDA-approved drugs with a view to repurposing, which can lead to rapid and relatively inexpensive development. From the Pharmakon-1600 library, 106 drugs were selected and tested against adult male parasites using a concentration of 1.25 × 10 M in an in vitro 5-day standard assay to assess motility and viability (using MTT/formazan colorimetry). The findings revealed that 44 drugs produced marginal/moderate activity (50-99% motility and/or MTT reductions) including cefuroxime sodium, methenamine, primaquine phosphate and rivastigmine tartrate, while 23 drugs produced good activity (100% motility reductions and significant MTT reductions), including atovaquone, isradipine, losartan, rifaximin, cefaclor and pyrantel pamoate. Although this study represents only a first step, some of the identified hits indicate there are potential anti- drug candidates worthy of further investigation.
PubMed: 38399264
DOI: 10.3390/pharmaceutics16020210 -
Current Research in Parasitology &... 2024Following the successful eradication of , there are now just three species of conventional microfilaremic human filarial parasites endemic to the Brazilian Amazon... (Review)
Review
Following the successful eradication of , there are now just three species of conventional microfilaremic human filarial parasites endemic to the Brazilian Amazon region: , and The zoonotic filarial parasite is also found in the Amazon region as are several sylvatic filarial parasites, some of which have been recorded causing zoonoses and some of which have never been recorded outside the region. is only found in the Amazonia onchocerciasis focus in the Brazilian state of Roraima where it affects the people of the Yanomami tribe living around the densely forested Venezuela border region. is by far the most common filarial parasite in Brazil and has a broad but patchy distribution throughout the western Amazon region. Recorded in the Brazilian states of Acre, Roraima, Matto Grosso, and within almost every municipality of Amazonas state, it is believed that pollution of the urban stream and river systems prevents the development of the simuliid vectors of and explains the parasite's reduced distribution within urban areas and an absence of recent reports from the state capital Manaus. Decades of WHO-led periodic ivermectin treatment of Yanomami tribe's people have resulted in the partial suppression of transmission in this focus and has also probably affected the transmission of in the region. , and very probably infections can all be treated and most likely cured with a 4-6-week treatment course of doxycycline. The Brazilian Ministry of Health does not, however, presently recommend any treatment for mansonellosis infections and thus parasitic infections outside the Amazonia focus are typically left untreated. While the long treatment courses required for doxycycline-based mansonellosis therapies preclude their use in control programmes, new fast-acting filarial drug treatments are likely to soon become available for the treatment of both onchocerciasis and mansonellosis in the Amazon region. Filarial disease management in the Brazilian Amazon is thus likely to become dramatically more viable at a time when the public health importance of these diseases is increasingly being recognized.
PubMed: 38283060
DOI: 10.1016/j.crpvbd.2023.100168 -
Epilepsia Open Apr 2024Epilepsy imposes a substantial burden on the Democratic Republic of Congo (DRC). These challenges encompass the lack of comprehensive disease surveillance, an unresolved... (Review)
Review
Epilepsy imposes a substantial burden on the Democratic Republic of Congo (DRC). These challenges encompass the lack of comprehensive disease surveillance, an unresolved understanding of its pathophysiology, economic barriers limiting access to essential care, the absence of epilepsy surgical capabilities, and deeply ingrained societal stigmas. Notably, the national prevalence of epilepsy remains undetermined, with research primarily concentrating on infectious factors like Onchocerca volvulus, leaving other potential causes underexplored. Most patients lack insurance, incurring out-of-pocket expenses that often lead them to opt for traditional medicine rather than clinical care. Social stigma, perpetuated by common misconceptions, intensifies the social isolation experienced by individuals living with epilepsy. Additionally, surgical interventions are unavailable, and the accessibility of anti-seizure medications and healthcare infrastructure remains inadequate. Effectively tackling these interrelated challenges requires a multifaceted approach, including conducting research into region-specific factors contributing to epilepsy, increasing healthcare funding, subsidizing the costs of treatment, deploying mobile tools for extensive screening, launching awareness campaigns to dispel myths and reduce stigma, and promoting collaborations between traditional healers and medical practitioners to enhance local understanding and epilepsy management. Despite the difficulties, significant progress can be achieved through sustained and compassionate efforts to understand and eliminate the barriers faced by epilepsy patients in the region. This review outlines essential steps for alleviating the epilepsy burden in the DRC. PLAIN LANGUAGE SUMMARY: There are not enough resources to treat epilepsy in the DRC. PWEs struggle with stigma and the lack of money. Many of them still use traditional medicine for treatment and hold wrong beliefs about epilepsy. That is why there is a need for more resources to make the lives of PWEs better in the DRC.
Topics: Animals; Humans; Democratic Republic of the Congo; Onchocerciasis; Onchocerca volvulus; Epilepsy; Risk Factors
PubMed: 38243880
DOI: 10.1002/epi4.12904 -
PLoS Neglected Tropical Diseases Dec 2023Onchocerca volvulus is a filarial parasite that is a major cause of dermatitis and blindness in endemic regions primarily in sub-Saharan Africa. Widespread efforts to...
BACKGROUND
Onchocerca volvulus is a filarial parasite that is a major cause of dermatitis and blindness in endemic regions primarily in sub-Saharan Africa. Widespread efforts to control the disease caused by O. volvulus infection (onchocerciasis) began in 1974 and in recent years, following successful elimination of transmission in much of the Americas, the focus of efforts in Africa has moved from control to the more challenging goal of elimination of transmission in all endemic countries. Mass drug administration (MDA) with ivermectin has reached more than 150 million people and elimination of transmission has been confirmed in four South American countries, with at least two African countries having now stopped MDA as they approach verification of elimination. It is essential that accurate data for active transmission are used to assist in making the critical decision to stop MDA, since missing low levels of transmission and infection can lead to continued spread or recrudescence of the disease.
METHODOLOGY/PRINCIPAL FINDINGS
Current World Health Organization guidelines for MDA stopping decisions and post-treatment surveillance include screening pools of the Simulium blackfly vector for the presence of O. volvulus larvae using a PCR-ELISA-based molecular technique. In this study, we address the potential of an updated, practical, standardized molecular diagnostic tool with increased sensitivity and species-specificity by comparing several candidate qPCR assays. When paired with heat-stable reagents, a qPCR assay with a mitochondrial DNA target (OvND5) was found to be more sensitive and species-specific than an O150 qPCR, which targets a non-protein coding repetitive DNA sequence. The OvND5 assay detected 19/20 pools of 100 blackfly heads spiked with a single L3, compared to 16/20 for the O150 qPCR assay.
CONCLUSIONS/SIGNIFICANCE
Given the improved sensitivity, species-specificity and resistance to PCR inhibitors, we identified OvND5 as the optimal target for field sample detection. All reagents for this assay can be shipped at room temperature with no loss of activity. The qPCR protocol we propose is also simpler, faster, and more cost-effective than the current end-point molecular assays.
Topics: Animals; Humans; DNA, Mitochondrial; Intestinal Volvulus; Ivermectin; Onchocerca; Onchocerca volvulus; Onchocerciasis; Simuliidae
PubMed: 38096317
DOI: 10.1371/journal.pntd.0011815 -
International Journal For Parasitology Mar 2024National programs in Africa have expanded their objectives from control of onchocerciasis (river blindness) as a public health problem to elimination of parasite...
National programs in Africa have expanded their objectives from control of onchocerciasis (river blindness) as a public health problem to elimination of parasite transmission, motivated by the reduction of Onchocerca volvulus infection prevalence in many African meso- and hyperendemic areas due to mass drug administration of ivermectin (MDAi). Given the large, contiguous hypo-, meso-, and hyperendemic areas, sustainable elimination of onchocerciasis in sub-Saharan Africa requires delineation of geographic boundaries for parasite transmission zones, so that programs can consider the risk of parasite re-introduction through vector or human migration from areas with ongoing transmission when making decisions to stop MDAi. We propose that transmission zone boundaries can be delineated by characterising the parasite genetic population structure within and between potential zones. We analysed whole mitochondrial genome sequences of 189 O. volvulus adults to determine the pattern of genetic similarity across three West African countries: Ghana, Mali, and Côte d'Ivoire. Population genetic structure indicates that parasites from villages near the Pru, Daka, and Black Volta rivers in central Ghana belong to one parasite population, indicating that the assumption that river basins constitute individual transmission zones is not supported by the data. Parasites from Mali and Côte d'Ivoire are genetically distinct from those from Ghana. This research provides the basis for developing tools for elimination programs to delineate transmission zones, to estimate the risk of parasite re-introduction via vector or human movement when intervention is stopped in one area while transmission is ongoing in others, to identify the origin of infections detected post-treatment cessation, and to investigate whether persisting prevalence despite ongoing interventions in one area is due to parasites imported from others.
Topics: Adult; Animals; Humans; Onchocerciasis; Onchocerca volvulus; Genome, Mitochondrial; Africa, Western; Ivermectin; Indans
PubMed: 37993016
DOI: 10.1016/j.ijpara.2023.11.002 -
BMC Infectious Diseases Nov 2023The World Health Organization has proposed that onchocerciasis elimination (interruption) of transmission be verified in 12 (approximately a third) endemic countries by...
BACKGROUND
The World Health Organization has proposed that onchocerciasis elimination (interruption) of transmission be verified in 12 (approximately a third) endemic countries by 2030. The strategy to reach this goal is based on ivermectin Mass Drug Administration (MDA) with high geographical and therapeutic coverage. In addition to coverage, high levels of treatment adherence are paramount. We investigated factors associated with ivermectin intake in an area of Ghana with persistent Onchocerca volvulus infection.
METHODS
In August 2021, a cross-sectional mixed-methods study was conducted in 13 onchocerciasis-endemic communities in the Bono Region of Ghana. Individuals aged ≥ 10 years were invited to participate in a questionnaire survey. A total of 48 focus group discussions and in-depth interviews with 10 community drug distributors and 13 community leaders were conducted.
RESULTS
A total of 510 people participated in the study [median age: 32, interquartile range 30 (20‒50) years]; 274 (53.7%) were females. Of the total, 320 (62.7%) declared that they adhered to each treatment round and 190 (37.3%) admitted they had not taken ivermectin during at least one MDA round, since becoming eligible for treatment. Of 483 participants with complete information, 139 (28.8%) did not take ivermectin during the last round (March 2021), and 24 (5.0%) had never taken ivermectin (systematic non-adherers). Reasons for not taking ivermectin included previous experience/fear of side-effects, being absent during MDA, pregnancy, the desire to drink alcohol, and drug distribution challenges. Being male, having good knowledge and perception of the disease, and not having secondary or higher level of formal education were significantly associated with higher odds of ivermectin intake.
CONCLUSIONS
A relatively high level of non-adherence to ivermectin treatment was documented. There is a need for targeted educational and behavioural change campaigns to reverse these trends and ensure a steady course toward meeting onchocerciasis elimination targets in Ghana.
Topics: Adult; Female; Humans; Male; Cross-Sectional Studies; Ghana; Ivermectin; Onchocerciasis; Persistent Infection; Medication Adherence
PubMed: 37974087
DOI: 10.1186/s12879-023-08806-8 -
The American Journal of Tropical... Dec 2023Onchocerciasis has been declared eliminated in Ecuador and surveillance measures are of great interest. In this study, we examined the infectivity rates of Simulium...
Onchocerciasis has been declared eliminated in Ecuador and surveillance measures are of great interest. In this study, we examined the infectivity rates of Simulium exiguum by Onchocerca volvulus in previously hyperendemic areas in Esmeraldas province of Ecuador. These areas had previously undergone mass administration of ivermectin, which led to the interruption of transmission in 2009 and the certification of elimination in 2014. The study included three communities in Río Cayapas and one in Río Canandé, and a total of 2,950 adult S. exiguum were collected in 2018. We used quantitative polymerase chain reaction with O. volvulus O-150 plasmid control DNA to analyze 59 pools. Our findings revealed that the infectivity rates were zero, indicating that the transmission of O. volvulus remained suspended in the area.
Topics: Humans; Animals; Adult; Onchocerciasis; Onchocerca volvulus; Real-Time Polymerase Chain Reaction; Ecuador; Intestinal Volvulus; Ivermectin; Simuliidae; Onchocerca
PubMed: 37931298
DOI: 10.4269/ajtmh.23-0435 -
Tropical Medicine & International... Nov 2023There is a pressing need to regularly evaluate the progress of onchocerciasis elimination programmes to timely identify and mitigate potential risks hindering the...
OBJECTIVES
There is a pressing need to regularly evaluate the progress of onchocerciasis elimination programmes to timely identify and mitigate potential risks hindering the reaching of the 2030 targets proposed by the World Health Organization (WHO) in its roadmap on neglected tropical diseases (NTDs). We determined the prevalence of onchocerciasis and associated dermatological and ophthalmological manifestations in six endemic communities in the Bono Region of Ghana after 27 years of ivermectin mass treatment.
METHODS
In a cross-sectional study, 564 participants aged ≥5 years were enrolled (49.1% females), with a median age of 26 (range: 5-89) years. In 54% and 47%, skin-snip microscopy and Ov16 rapid diagnostic tests were performed, respectively. Skin disease was determined using the WHO Skin NTD App. Visual function assessments included tests of visual acuity.
RESULTS
The overall microfilarial prevalence was 12.5% (38/305) and Ov16 seroprevalence was 24.2% (64/265). Severe itching was recorded in 24.3%, acute papular onchodermatitis in 52.8%, chronic papular onchodermatitis in 12.5%, lichenified onchodermatitis in 0.7%, skin atrophy in 11.3%, depigmentation in 1.7% and palpable nodules in 5.3%. Of the 301 persons in which visual acuity was examined, 17% were visually impaired and 5.3% were blind and 47.3% presented with cataract. Chronic papular onchodermatitis, lichenified onchodermatitis, depigmentation and visual impairment were significantly associated with the presence of skin microfilariae and Ov16 seropositivity.
CONCLUSIONS
The persistence of Onchocerca volvulus infection and onchocerciasis-associated dermatological and ophthalmological pathologies after prolonged treatment is of concern. There is a need to include morbidity management in onchocerciasis elimination programmes and understand better patterns of treatment coverage, adherence and actual intake of ivermectin.
Topics: Female; Humans; Child, Preschool; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Male; Onchocerciasis; Ivermectin; Ghana; Mass Drug Administration; Cross-Sectional Studies; Seroepidemiologic Studies; Prevalence; Neglected Diseases
PubMed: 37846505
DOI: 10.1111/tmi.13937 -
Tropical Medicine and Infectious Disease Sep 2023WHO and endemic countries target elimination of transmission of , the parasite causing onchocerciasis. Population genetic analysis of may provide data to improve the...
WHO and endemic countries target elimination of transmission of , the parasite causing onchocerciasis. Population genetic analysis of may provide data to improve the evidence base for decisions on when, where, and for how long to deploy which interventions and post-intervention surveillance to achieve elimination. Development of necessary methods and tools requires parasites suitable for genetic analysis. Based on our experience with microfilariae obtained from different collaborators, we developed a microfilariae transfer procedure for large-scale studies in the Democratic Republic of Congo (DRC) comparing safety and efficacy of ivermectin, the mainstay of current onchocerciasis elimination strategies, and moxidectin, a new drug. This procedure is designed to increase the percentage of microfilariae in skin snips suitable for genetic analysis, improve assignment to metadata, and minimize time and materials needed by the researchers collecting the microfilariae. Among 664 microfilariae from South Sudan, 35.7% and 39.5% failed the mitochondrial and nuclear qPCR assay. Among the 576 microfilariae from DRC, 16.0% and 16.7% failed these assays, respectively. This difference may not only be related to the microfilariae transfer procedure but also to other factors, notably the ethanol concentration in the tubes in which microfilariae were stored (64% vs. ≥75%).
PubMed: 37755906
DOI: 10.3390/tropicalmed8090445 -
Brain Communications 2023Nodding syndrome is a neglected, disabling and potentially fatal epileptic disorder of unknown aetiology affecting thousands of individuals mostly confined to Eastern...
Nodding syndrome is a neglected, disabling and potentially fatal epileptic disorder of unknown aetiology affecting thousands of individuals mostly confined to Eastern sub-Saharan Africa. Previous studies have identified multiple associations-including , antileiomodin-1 antibodies, vitamin B deficiency and measles virus infection-yet, none is proven causal. We conducted a case-control study of children with early-stage nodding syndrome (symptom onset <1 year). Cases and controls were identified through a household survey in the Greater Mundri area in South Sudan. A wide range of parasitic, bacterial, viral, immune-mediated, metabolic and nutritional risk factors was investigated using conventional and state-of-the-art untargeted assays. Associations were examined by multiple logistic regression analysis, and a hypothetical causal model was constructed using structural equation modelling. Of 607 children with nodding syndrome, 72 with early-stage disease were included as cases and matched to 65 household- and 44 community controls. infection (odds ratio 7.04, 95% confidence interval 2.28-21.7), infection (odds ratio 2.33, 95% confidence interval 1.02-5.3), higher antimalarial seroreactivity (odds ratio 1.75, 95% confidence interval 1.20-2.57), higher vitamin E concentration (odds ratio 1.53 per standard deviation increase, 95% confidence interval 1.07-2.19) and lower vitamin B concentration (odds ratio 0.56 per standard deviation increase, 95% confidence interval 0.36-0.87) were associated with higher odds of nodding syndrome. In a structural equation model, we hypothesized that infection, higher vitamin E concentration and fewer viral exposures increased the risk of nodding syndrome while lower vitamin B concentration, and malaria infections resulted from having nodding syndrome. We found no evidence that antileiomodin-1 antibodies, vitamin B and other factors were associated with nodding syndrome. Our results argue against several previous causal hypotheses including . Instead, nodding syndrome may be caused by a complex interplay between multiple pathogens and nutrient levels. Further studies need to confirm these associations and determine the direction of effect.
PubMed: 37731906
DOI: 10.1093/braincomms/fcad223