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1.
PLoS Negl Trop Dis ; 15(10): e0009812, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34637436

RESUMEN

BACKGROUND: Molecular xenomonitoring (MX), the detection of parasite nucleic acid in the vector population, is recommended for onchocerciasis surveillance in elimination settings. However, the sensitivity of MX for detecting onchocerciasis-positive communities has not previously been evaluated. MX may have additional applications for control programmes but its utility is restricted by a limited understanding of the relationship between MX results and human prevalence. METHODS: We conducted a systematic review of studies reporting the prevalence of Onchocerca volvulus DNA in wild-caught Simulium spp. flies (MX rate) and corresponding prevalence of microfilaria (mf) in humans. We evaluated the sensitivity of MX for detecting onchocerciasis-positive communities and describe the characteristics of studies with reduced sensitivity. We conducted a linear regression to evaluate the relationship between mf prevalence and MX rate. RESULTS: We identified 15 relevant studies, with 13 studies comprising 34 study communities included in the quantitative analyses. Most communities were at advanced stages towards elimination and had no or extremely low human prevalence. MX detected positive flies in every study area with >1% mf prevalence, with the exception of one study conducted in the Venezuelan Amazonian focus. We identified a significant relationship between the two measurements, with mf prevalence accounting for half of the variation in MX rate (R2 0.50, p<0.001). CONCLUSION: MX is sensitive to communities with ongoing onchocerciasis transmission. It has potential to predict human mf prevalence, but further data is required to understand this relationship, particularly from MX surveys conducted earlier in control programmes before transmission has been interrupted.

2.
Parasitol Res ; 2021 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-34642800

RESUMEN

Twenty diseases are recognized as neglected tropical diseases (NTDs) by World Health Assembly resolutions, including human filarial diseases. The end of NTDs is embedded within the Sustainable Development Goals for 2030, under target 3.3. Onchocerciasis afflicts approximately 20.9 million people worldwide with > 90% of those infected residing in Africa. Control programs have made tremendous efforts in the management of onchocerciasis by mass drug administration and aerial larviciding; however, disease elimination is not yet achieved. In the new WHO roadmap, it is recognized that new drugs or drug regimens that kill or permanently sterilize adult filarial worms would significantly improve elimination timelines and accelerate the achievement of the program goal of disease elimination. Drug development is, however, handicapped by high attrition rates, and many promising molecules fail in preclinical development or in subsequent toxicological, safety and efficacy testing; thus, research and development (R&D) costs are, in aggregate, very high. Drug discovery and development for NTDs is largely driven by unmet medical needs put forward by the global health community; the area is underfunded and since no high return on investment is possible, there is no dedicated drug development pipeline for human filariasis. Repurposing existing drugs is one approach to filling the drug development pipeline for human filariasis. The high cost and slow pace of discovery and development of new drugs has led to the repurposing of "old" drugs, as this is more cost-effective and allows development timelines to be shortened. However, even if a drug is marketed for a human or veterinary indication, the safety margin and dosing regimen will need to be re-evaluated to determine the risk in humans. Drug repurposing is a promising approach to enlarging the pool of active molecules in the drug development pipeline. Another consideration when providing new treatment options is the use of combinations, which is not addressed in this review. We here summarize recent advances in the late preclinical or early clinical stage in the search for a potent macrofilaricide, including drugs against the nematode and against its endosymbiont, Wolbachia pipientis.

3.
Pathogens ; 10(10)2021 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-34684277

RESUMEN

BACKGROUND: High ongoing Onchocerca volvulus transmission was recently documented in Maridi County, South Sudan. To complement community-directed treatment with ivermectin (CDTI) as the main onchocerciasis control strategy, we initiated a community-based vector control method "slash and clear" at the Maridi dam, a Simulium damnosum s.l. breeding site, to reduce O. volvulus transmission. METHODS: Simulium damnosum s.l. biting rates were collected before and during the twenty months following the "slash and clear" intervention using the human landing catches. Black flies were dissected to measure parity rates before and twelve months after the intervention. Larvae and pupae of S. damnosum s.l. were collected from the dam for morphological and chromosomal characterization to identify the cytospecies involved. RESULTS: Biting rates of S. damnosum s.l. close to the Maridi dam spillway decreased by >90% post-"slash and clear" for more than six months. Twelve months after the "slash and clear" intervention, the reduction in biting rates was still at <50% (p = 0.0007). Parity rates reduced from 13% pre-"slash and clear" (November 2019) to 5.6% post-"slash and clear" (November 2020). Larvae collected from the dam were identified as Simulium sirbanum. CONCLUSION: The "slash and clear" method was found to be an effective and cheap community-based method to reduce black fly biting rates caused by S. sirbanum. When repeated at least annually together with a high CDTI coverage, this intervention has the potential to considerably accelerate onchocerciasis elimination.

4.
Parasitol Res ; 120(11): 3633-3644, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34519871

RESUMEN

Diverse Onchocerca species are present mostly parasitizing ungulates, with the exception of Onchocerca volvulus (O. volvulus) in humans and O. lupi in canids and cats. The human cases due to the O. lupi have been more highlighted during last years. So, the present review was performed to determine the detailed characteristics of confirmed human O. lupi case reports documented worldwide. Hence, a systematic search was done using English international databases (Scopus, PubMed, Web of Science, Embase, ProQuest, and Google Scholar). Totally, 14 confirmed human cases were documented during the last decade, mostly from the USA and Turkey with 7 and 3 cases, respectively. Most cases (7 individuals) were male with the age range of 22-month-old to 54-year-old. The parasite was frequently isolated from the right eye (5 cases), followed by the left eye (4 cases), cervical spinal canal (3 cases), scalp, and right forearm (one case each). Molecular identification of the isolated agent was the preferred way of diagnosis in most cases (9 records). In conclusion, human O. lupi cases have been more highlighted in recent years, whether due to the improved diagnostics and/or host-switching phenomenon, and both veterinarians and healthcare authorities should be alerted.

5.
Am J Trop Med Hyg ; 2021 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-34544040

RESUMEN

We report a case of human ocular onchocerciasis by zoonotic Onchocerca lupi presenting as nodular scleritis. Molecular analyses were used to confirm diagnosis at species level. In addition to few existing reports of human infection by O. lupi in Turkey, this case further suggests that the pathogen might be more common than previously reported, thus requiring further attention and investigations.

6.
BMJ Open ; 11(9): e050341, 2021 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-34475178

RESUMEN

INTRODUCTION: Onchocerciasis, caused by the filarial nematode Onchocerca volvulus, remains endemic in Cameroon despite decades of community-directed treatment with ivermectin (CDTI). CDTI is often hampered by coendemicity with loiasis (another filariasis caused by Loa loa) in some areas. Strong epidemiological evidence suggests that O. volvulus infection increases the risk for onchocerciasis-associated epilepsy (OAE) among Cameroonian children. This highlights the urgent need to strengthen onchocerciasis elimination programmes in mesoendemic/hyperendemic areas. Novel alternative strategies, such as the 'slash and clear' (S&C) vector control method, may be required to complement ongoing CDTI to accelerate elimination of transmission. The short-term impact of S&C on the biting rates of the blackfly vectors has been demonstrated in other settings. However, its long-term effectiveness and impact on parasitological and serological markers of onchocerciasis transmission as well as on OAE are still unknown. METHODS AND ANALYSIS: We aim to assess the effectiveness of annual S&C interventions combined with CDTI in reducing onchocerciasis transmission and epilepsy incidence. Eight onchocerciasis-endemic villages located <5 km from the Mbam or Sanaga rivers will be randomised to two arms: four villages will receive yearly CDTI only for two consecutive years (Arm 1), while the other four villages will receive CDTI plus annual S&C for 2 years (Arm 2). Study outcomes (blackfly biting rates, infectivity rates and seroprevalence of onchocerciasis antibodies (Ov16 antibodies) in children, prevalence of microfilaridermia and epilepsy incidence) will be monitored prospectively and compared across study arms. We expect that S&C will have an added benefit over CDTI alone. ETHICS AND DISSEMINATION: The protocol has received ethical approval from the institutional review board of the Cameroon Baptist Convention Health Board (reference number: IRB2021-03) and has been registered with the Pan African Clinical Trials Registry. Findings will be disseminated at national and international levels via meetings and peer-reviewed publications. TRIAL REGISTRATION NUMBER: PACTR202101751275357.


Asunto(s)
Epilepsia , Oncocercosis , Niño , Humanos , Incidencia , Ivermectina/uso terapéutico , Oncocercosis/tratamiento farmacológico , Oncocercosis/epidemiología , Oncocercosis/prevención & control , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Seroepidemiológicos
7.
Parasit Vectors ; 14(1): 478, 2021 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-34526130

RESUMEN

BACKGROUND: Black flies (Diptera: Simuliidae) serve as arthropod vectors for various species of Onchocerca (Nematoda: Onchocercidae) that may be associated with disease in humans, domestic animals, and wildlife. The emergence of zoonotic Onchocerca lupi in North America and reports of cervid-associated zoonotic onchocerciasis by Onchocerca jakutensis highlight the need for increased entomological surveillance. In addition, there is mounting evidence that Onchocerca diversity in North America is far greater than previously thought, currently regarded as Onchocerca cervipedis species complex. This study reports new geographic records and black fly vector associations of an uncharacterized Onchocerca species. METHODS: To better understand the biodiversity and geographic distribution of Onchocerca, 485 female black flies (2015: 150, 2016: 335) were collected using CO2-baited traps from February to October 2015-2016 in Lake County, northern California, USA. Individual flies were morphologically identified and pooled (≤ 10 individuals) by species, collection date, and trap location. Black fly pools were processed for DNA extraction, and subsequent PCR and sequencing targeting of the NADH dehydrogenase subunit 5 gene of filarioids. RESULTS: Among the pools of black flies, there were 158 individuals of Simulium tescorum (2015: 57, 2016: 101), 302 individuals of Simulium vittatum (sensu lato [s.l.]) (2015: 82, 2016: 220), 16 individuals of Simulium clarum "black" phenotype (2015: 5, 2016: 11), and 13 individuals of S. clarum "orange" phenotype (2015: 6, 2016: 7). PCR analysis revealed the percentage of filarioid-positive pools were 7.50% (n = 3) for S. tescorum, 3.75% (n = 3) for S. vittatum (s.l., likely S. tribulatum), 7.69% (n = 1) for S. clarum "black" phenotype, and no positives for S. clarum "orange" phenotype. Genetic distance and phylogenetic analyses suggest that the northern California Onchocerca isolates belong to the same species reported in black flies from southern California (average pairwise comparison: 0.32%), and seem closely related to Onchocerca isolates of white-tailed deer from upstate New York (average pairwise comparison: 2.31%). CONCLUSION: A cryptic Onchocerca species was found in Lake County, California, and may be a part of a larger, continentally distributed species complex rather than a single described species of North America. In addition, there are at least three putative vectors of black flies (S. clarum, S. tescorum, S. vittatum) associated with this cryptic Onchocerca species. A comprehensive reassessment of North American Onchocerca biodiversity, host, and geographic range is necessary.

8.
Expert Rev Vaccines ; : 1-12, 2021 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-34488533

RESUMEN

INTRODUCTION: Human onchocerciasis caused by the filarial nematode parasite Onchocerca volvulus remains a major cause of debilitating disease infecting millions primarily in Sub-Saharan Africa. The development of a prophylactic vaccine, along with mass drug administration, would facilitate meeting the goal of onchocerciasis elimination by 2030. AREAS COVERED: Models used to study immunity to Onchocerca include natural infection of cattle with Onchocerca ochengi and O. volvulus infective third-stage larvae implanted within diffusion chambers in mice. A vaccine, comprised of two adjuvanted recombinant antigens, induced protective immunity in genetically diverse mice suggesting that it will function similarly in diverse human populations. These antigens were recognized by immune humans and also induced protective immunity against Brugia malayi. We describe the development of a fusion protein composed of the two vaccine antigens with the plan to test the vaccine in cows and non-human primates as a prelude to the initiation of phase 1 clinical trials. EXPERT OPINION: The adjuvanted O. volvulus vaccine composed of two antigens Ov-103 and Ov-RAL-2 was shown to be consistently effective at inducing protective immunity using multiple immune mechanisms. The vaccine is ready for further evaluation in other animal models before moving to clinical trials in humans.

9.
Exp Parasitol ; 229: 108143, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34437906

RESUMEN

BACKGROUND: Current treatment options for onchocerciasis are sub-optimal, prompting research and development of a safe cure (macrofilaricide). Onchocerca ochengi, a parasite of cattle, is used as a close surrogate for the human parasite O. volvulus in a murine model for pre-clinical screening of macrofilaricides. Skin from naturally infected cattle have been used in previous studies as a reliable source of parasite material. However, there is limited knowledge on how source-related factors such as the microfilaridermia status of the cattle, the nodule load and nodular worm viability may affect survival of male O. ochengi worms implanted in the rodent hosts. Such relationships were investigated in this study. METHODS: Dermal tissue and nodules were obtained from Gudali cattle, dissected and cultured to obtain migrating microfilariae (mf) and male worms. Emerged male worms were implanted into SCID mice and Gerbils (Meriones unguiculatus) and recovery rates were determined upon 42 days post implantation. Finally, nodules were processed for histology and embryogram analyses to assess the nodular worm viability and fertility, respectively. RESULTS: Of the 69 cattle sampled, 24 (34.8%) were mf+ and 45 (65.2%) were mf-. The mean nodule loads were 180.5 ± 117.7 (mf+) and 110.6 ± 102.7 (mf-) (p = 0.0186). The mean male worm harvest from nodules were 76.8 ± 120.3 and 47.2 ± 33.4 (p = 0.2488) for mf+ and mf- cattle, respectively. The number of male worms per 100 nodules were 57/100 and 46/100 nodules for mf+ and mf- cows, respectively. Female worms from nodules of mf- cows had higher counts of both normal and abnormal embryos with higher proportions of dead nodular worms evinced by histology compared to those from mf+ cows. A total of 651 worms were implanted into mice and gerbils, out of which 129 (19.81%) were recovered. Logistic regression analysis indicated that the microfilaridermia status of the cattle (presence of mf) (OR = 4.3319; P = 0.001) is the single most important predictor of the success of male worm recovery after implantation into rodents. CONCLUSION: Microfilaridermic cattle provide a promising source of adult O. ochengi. Male worms from this group of cattle have a better success rate of survival in a murine implant model. Nevertheless, in the programmatic point of view, amicrofilaridermic Gudali cattle would still constitute an important source of O. ochengi male worms with relatively good viability after implantation into rodents.


Asunto(s)
Enfermedades de los Bovinos/parasitología , Onchocerca/fisiología , Oncocercosis/veterinaria , Animales , Bovinos , Modelos Animales de Enfermedad , Femenino , Fertilidad , Gerbillinae , Masculino , Ratones , Ratones SCID , Microfilarias/crecimiento & desarrollo , Microfilarias/fisiología , Análisis Multivariante , Onchocerca/crecimiento & desarrollo , Oncocercosis/parasitología , Análisis de Regresión
10.
Parasit Vectors ; 14(1): 397, 2021 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-34380554

RESUMEN

BACKGROUND: The tropical disease onchocerciasis (river blindness), caused by Onchocerca volvulus filarial nematodes, is targeted for elimination by mass treatment with nematocidal and antimicrobial drugs. Diagnosis of O. volvulus infections is based on counts of skin-borne microfilariae, but additional diagnostic tools, e.g. worm- or host-derived small RNAs, proteins or metabolites, are required for high-throughput screening. N-acetyltyramine-O,ß-glucuronide (NATOG) was suggested as a biomarker for onchocerciasis but its viability as diagnostic tool has been challenged. METHODS: We performed a screening program of urine samples from individuals from Cameroon infected with O. volvulus, Loa loa, Mansonella perstans or a combination thereof. Urine metabolites were measured by liquid chromatography-mass spectrometry (LC-MS). Principle component analysis (PCA) revealed that onchocerciasis causes complex changes of the urine metabolome. RESULTS: The mean NATOG content was elevated in urine of O. volvulus-infected compared with non-infected individuals, but NATOG levels showed considerable variation. However, 13.8% of all O. volvulus-infected individuals had high NATOG levels never reached by individuals without filarial infections or only infected with L. loa or M. perstans. Therefore, the identification of individuals with high NATOG levels might be used to screen for the elimination of onchocerciasis after mass drug application. Additional metabolites, including a compound identified as cinnamoylglycine, had high PC1/PC2 loadings in the data set. Mean levels of cinnamoylglycine were increased in O. volvulus-infected individuals, and 17.2% of all O. volvulus individuals had elevated cinnamoylglycine levels not reached by the controls. CONCLUSIONS: On an individual level, NATOG alone had poor discriminative power distinguishing infected from non-infected individuals. However, 13.8% of all O. volvulus-infected individuals had NATOG levels never reached by individuals without filarial infections or infected with only L. loa or M. perstans. Discrimination of O. volvulus infections from controls or individuals suffering from multiple infections was improved by the measurement of additional metabolites, e.g. cinnamoylglycine. Thus, measuring a combination of urine metabolites may provide a way to assess onchocerciasis on the population level. This provides the possibility to design a strategy for large-scale onchocerciasis epidemiological screening programs based on urine rather than invasive techniques.

11.
Mitochondrial DNA B Resour ; 6(9): 2572-2574, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34377832

RESUMEN

Onchocerca lupi, Rodonaja 1967, is an emerging, zoonotic filarial nematode parasite that causes ocular disease in dogs, cats, wild canids, and humans. It is the causative agent of ocular onchocercosis in canines with increasing incidence in both North America and the Old World during the early twenty-first century. We report the complete mitochondrial genome of an O. lupi isolate from a dog from Arizona, southwestern USA, and its genetic differentiation from related Onchocerca species. The whole mitochondrial genome was obtained from whole genome sequencing of genomic DNA isolated from an adult worm. This mitogenome is 13,766 bp in size and contains 36 genes and a control region. This mitogenome provides a valuable resource for future studies involving epidemiological surveillance, population genetics, phylogeography, and comparative mitogenomics of this emerging pathogen and other parasitic nematodes.

12.
Trop Med Infect Dis ; 6(3)2021 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-34449738

RESUMEN

One of the most debilitating consequences of aging is the progressive decline in immune function, known as immunosenescence. This phenomenon is characterized by a shift in T-cell phenotypes, with a manifest decrease of naive T-cells-dealing with newly encountered antigens-and a concomitant accumulation of senescent and regulatory T-cells, leading to a greater risk of morbidity and mortality in older subjects. Additionally, with aging, several studies have unequivocally revealed an increase in the prevalence of onchocerciasis infection. Most lymphatic complications, skin and eye lesions due to onchocerciasis are more frequent among the elderly population. While the reasons for increased susceptibility to onchocerciasis with age are likely to be multi-factorial, age-associated immune dysfunction could play a key role in the onset and progression of the disease. On the other hand, there is a growing consensus that infection with onchocerciasis may evoke deleterious effects on the host's immunity and exacerbate immune dysfunction. Indeed, Onchocerca volvulus has been reported to counteract the immune responses of the host through molecular mimicry by impairing T-cell activation and interfering with the processing of antigens. Moreover, reports indicate impaired cellular and humoral immune responses even to non-parasite antigens in onchocerciasis patients. This diminished protective response may intensify the immunosenescence outcomes, with a consequent vulnerability of those affected to additional diseases. Taken together, this review is aimed at contributing to a better understanding of the immunological and potential pathological mechanisms of onchocerciasis in the older population.

13.
Pathogens ; 10(7)2021 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-34357995

RESUMEN

Nodding syndrome has been suggested to be triggered by neurotoxic leiomodin-1 auto-antibodies cross-reacting with Onchocerca volvulus. Here, we screened serum and CSF samples of persons with nodding syndrome and other forms of onchocerciasis-associated epilepsy (OAE) and African and European controls for leiomodin-1 antibodies by a cell-based assay (CBA) and Western blot (WB). These samples were also investigated for the presence of auto-antibodies cross-reacting with rat brain tissue by immunohistochemistry (IHC). Additionally, IHC was used to detect the leiomodin-1 protein in post-mortem brain samples of persons with OAE who died. Leiomodin-1 antibodies were detected by CBA in 6/52 (12%) and by WB in 23/54 (43%) persons with OAE compared to in 14/61 (23%) (p = 0.113) and 23/54 (43%) (p = 0.479) of controls without epilepsy. Multivariable exact logistic regression did not show an association between O. volvulus infection or epilepsy status and the presence of leiomodin-1. Leiomodin-1 antibodies were not detected in 12 CSF samples from persons with OAE or in 16 CSF samples from persons with acute-onset neurological conditions, as well as not being detected in serum from European controls. Moreover, the leiomodin-1 protein was only detected in capillary walls in post-mortem brain tissues and not in brain cells. IHC on rat brain slides with serum samples from persons with OAE or controls from persons with or without O. volvulus infection revealed no specific staining pattern. In conclusion, our data do not support OAE to be an autoimmune disorder caused by leiomodin-1 antibodies.

14.
PLoS Negl Trop Dis ; 15(7): e0009604, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34310602

RESUMEN

BACKGROUND: Onchocerciasis ("river blindness") can cause severe morbidity, including vision loss and various skin manifestations, and is targeted for elimination using ivermectin mass drug administration (MDA). We calculated the number of people with Onchocerca volvulus infection and onchocercal skin and eye disease as well as disability-adjusted life years (DALYs) lost from 1990 through to 2030 in areas formerly covered by the African Programme for Onchocerciasis Control. METHODS: Per MDA implementation unit, we collated data on the pre-control distribution of microfilariae (mf) prevalence and the history of control. Next, we predicted trends in infection and morbidity over time using the ONCHOSIM simulation model. DALY estimates were calculated using disability weights from the Global Burden of Disease Study. RESULTS: In 1990, prior to MDA implementation, the total population at risk was 79.8 million with 26.0 million (32.5%) mf-positive individuals, of whom 17.5 million (21.9%) had some form of onchocercal skin or eye disease (2.5 million DALYs lost). By 2030, the total population was predicted to increase to 236.1 million, while the number of mf-positive cases (about 6.8 million, 2.9%), people with skin or eye morbidity (4.2 million, 1.8%), and DALYs lost (0.7 million) were predicted to decline. CONCLUSIONS: MDA has had a remarkable impact on the onchocerciasis burden in countries previously under the APOC mandate. In the few countries where we predict continued transmission between now and 2030, intensified MDA could be combined with local vector control efforts, or the introduction of new drugs for mopping up residual cases of infection and morbidity.


Asunto(s)
Antiparasitarios/uso terapéutico , Ivermectina/uso terapéutico , Oncocercosis Ocular/patología , Enfermedades Cutáneas Parasitarias/patología , África del Sur del Sahara/epidemiología , Antiparasitarios/administración & dosificación , Humanos , Ivermectina/administración & dosificación , Administración Masiva de Medicamentos , Modelos Biológicos , Oncocercosis Ocular/tratamiento farmacológico , Oncocercosis Ocular/epidemiología , Factores de Riesgo , Enfermedades Cutáneas Parasitarias/tratamiento farmacológico , Enfermedades Cutáneas Parasitarias/epidemiología
15.
PLoS Negl Trop Dis ; 15(7): e0008824, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34319976

RESUMEN

Recent evidence suggests that, in some foci, elimination of onchocerciasis from Africa may be feasible with mass drug administration (MDA) of ivermectin. To achieve continental elimination of transmission, mapping surveys will need to be conducted across all implementation units (IUs) for which endemicity status is currently unknown. Using boosted regression tree models with optimised hyperparameter selection, we estimated environmental suitability for onchocerciasis at the 5 × 5-km resolution across Africa. In order to classify IUs that include locations that are environmentally suitable, we used receiver operating characteristic (ROC) analysis to identify an optimal threshold for suitability concordant with locations where onchocerciasis has been previously detected. This threshold value was then used to classify IUs (more suitable or less suitable) based on the location within the IU with the largest mean prediction. Mean estimates of environmental suitability suggest large areas across West and Central Africa, as well as focal areas of East Africa, are suitable for onchocerciasis transmission, consistent with the presence of current control and elimination of transmission efforts. The ROC analysis identified a mean environmental suitability index of 0·71 as a threshold to classify based on the location with the largest mean prediction within the IU. Of the IUs considered for mapping surveys, 50·2% exceed this threshold for suitability in at least one 5 × 5-km location. The formidable scale of data collection required to map onchocerciasis endemicity across the African continent presents an opportunity to use spatial data to identify areas likely to be suitable for onchocerciasis transmission. National onchocerciasis elimination programmes may wish to consider prioritising these IUs for mapping surveys as human resources, laboratory capacity, and programmatic schedules may constrain survey implementation, and possibly delaying MDA initiation in areas that would ultimately qualify.


Asunto(s)
Erradicación de la Enfermedad , Oncocercosis/epidemiología , África/epidemiología , Ambiente , Predicción , Humanos , Ivermectina/administración & dosificación , Administración Masiva de Medicamentos , Oncocercosis/tratamiento farmacológico , Oncocercosis/transmisión , Curva ROC
16.
PLoS Pathog ; 17(7): e1009682, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34293063

RESUMEN

Current mass drug administration (MDA) programs for the treatment of human river blindness (onchocerciasis) caused by the filarial worm Onchocerca volvulus rely on ivermectin, an anthelmintic originally developed for animal health. These treatments are primarily directed against migrating microfilariae and also suppress fecundity for several months, but fail to eliminate adult O. volvulus. Therefore, elimination programs need time frames of decades, well exceeding the life span of adult worms. The situation is worsened by decreased ivermectin efficacy after long-term therapy. To improve treatment options against onchocerciasis, a drug development candidate should ideally kill or irreversibly sterilize adult worms. Emodepside is a broad-spectrum anthelmintic used for the treatment of parasitic nematodes in cats and dogs (Profender and Procox). Our current knowledge of the pharmacology of emodepside is the result of more than 2 decades of intensive collaborative research between academia and the pharmaceutical industry. Emodepside has a novel mode of action with a broad spectrum of activity, including against extraintestinal nematode stages such as migrating larvae or macrofilariae. Therefore, emodepside is considered to be among the most promising candidates for evaluation as an adulticide treatment against onchocerciasis. Consequently, in 2014, Bayer and the Drugs for Neglected Diseases initiative (DNDi) started a collaboration to develop emodepside for the treatment of patients suffering from the disease. Macrofilaricidal activity has been demonstrated in various models, including Onchocerca ochengi in cattle, the parasite most closely related to O. volvulus. Emodepside has now successfully passed Phase I clinical trials, and a Phase II study is planned. This Bayer-DNDi partnership is an outstanding example of "One World Health," in which experience gained in veterinary science and drug development is translated to human health and leads to improved tools to combat neglected tropical diseases (NTDs) and shorten development pathways and timelines in an otherwise neglected area.

17.
Pathogens ; 10(6)2021 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-34201076

RESUMEN

Onchocerciasis-associated epilepsy (OAE) is a devastating childhood disorder occurring in areas with high Onchocerca volvulus transmission. Despite epidemiological evidence showing the association between O. volvulus and epilepsy, the underlying mechanism remains unknown. Since high levels of serotonin are known to induce seizures, we investigated serotonin levels in persons with OAE and controls selected from the Democratic Republic of Congo. Serum serotonin levels were determined by ELISA in 19 persons with OAE, 32 persons with epilepsy without O. volvulus infection, 18 with O. volvulus infection but without epilepsy, and 35 with neither O. volvulus infection nor epilepsy. O. volvulus infection was diagnosed by skin snip testing and/or OV16 antibody detection. Serum serotonin levels were significantly decreased in persons with OAE compared to persons with O. volvulus infection and no epilepsy. In conclusion, an increased serotonin level is unable to explain the pathogenesis of OAE. Other hypotheses to identify the causal mechanism of OAE will need to be investigated.

18.
Yale J Biol Med ; 94(2): 331-341, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34211352

RESUMEN

The parasitic filarioid Onchocerca lupi causes ocular disease characterized by conjunctivitis and nodular lesions. This nematode was first described in 1967 in a wolf from Georgia, and since then cases of infection from dogs and cats with ocular onchocercosis and sporadically from humans also with subcutaneous and cervical lesions caused by O. lupi have been reported from the Middle East, Europe, and North America. Due to its zoonotic potential, this parasitic infection has gained attention in the past 20 years. Phylogenetic studies have highlighted the recent divergence of O. lupi from other Onchocerca spp. and the importance of domestication in the evolutionary history of this worm. Moreover, the finding of an O. lupi genotype associated with subclinical and mild infection in the Iberian Peninsula, raises important questions about the pathogenicity of this presently enigmatic parasite.

19.
Acta Parasitol ; 2021 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-34279775

RESUMEN

PURPOSE: The occurrence of Single-Nucleotide Polymorphisms (SNPs) associated with repeated ivermectin treatment and sub-optimal responses reported by previous findings is of great concern in Onchocerciasis endemic areas. This study investigated SNPs' occurrence after 15 years of ivermectin intervention in Onchocerciasis endemic communities in two Local Government Areas of Taraba State, Nigeria. METHODS: Microfilariae samples were collected by skin snip from individuals treated with ivermectin for 10-15 years of annual distribution and preserved in RNAlater® in a 1.5 ml micro-centrifuge tube. Genomic DNA was extracted from microfilariae and residual skin, amplification in two regions within the ß-tubulin gene, sequenced and analyzed for SNPs using Bioinformatics tools. RESULTS: Three distinct SNP positions: 1183 (T/G), 1188 (T/C) and 1308 (C/T) on the ß-tubulin gene on the targeted 1083-1568 bp fragment, associate's with the ivermectin-treated population. Furthermore, SNPs positions detected in this study are 1730 (A/G) and 1794 (T/G) in the ß-tub gene in the 1557-1857 (bp) region. The 1794 (T/G) SNP position (Phe243Val) in the exon within the ß-tubulin gene region were observed in this study. CONCLUSION: The present study indicates that SNPs are observed in Onchocerca volvulus, thus strengthening the warning that genetic changes could occur in some parasite populations in some ivermectin-treated areas.

20.
Pathogens ; 10(7)2021 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-34206564

RESUMEN

Despite the increasing epidemiological evidence that the Onchocerca volvulus parasite is strongly associated with epilepsy in children, hence the name onchocerciasis-associated epilepsy (OAE), the pathophysiological mechanism of OAE remains to be elucidated. In June 2014, children with unprovoked convulsive epilepsy and healthy controls were enrolled in a case control study in Titule, Bas-Uélé Province in the Democratic Republic of the Congo (DRC) to identify risk factors for epilepsy. Using a subset of samples collected from individuals enrolled in this study (16 persons with OAE and 9 controls) plasma, buffy coat, and cerebrospinal fluid (CSF) were subjected to random-primed next-generation sequencing. The resulting sequences were analyzed using sensitive computational methods to identify viral DNA and RNA sequences. Anneloviridae, Flaviviridae, Hepadnaviridae (Hepatitis B virus), Herpesviridae, Papillomaviridae, Polyomaviridae (Human polyomavirus), and Virgaviridae were identified in cases and in controls. Not unexpectedly, a variety of bacteriophages were also detected in all cases and controls. However, none of the identified viral sequences were found enriched in OAE cases, which was our criteria for agents that might play a role in the etiology or pathogenesis of OAE.

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