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Current Neurology and Neuroscience... Apr 2022Neurocysticercosis (NCC) has been well recognized as a leading cause of epilepsy. More recently, studies of other parasitic diseases such as cerebral malaria (CM)... (Review)
Review
PURPOSE OF THE REVIEW
Neurocysticercosis (NCC) has been well recognized as a leading cause of epilepsy. More recently, studies of other parasitic diseases such as cerebral malaria (CM) and onchocerciasis are yielding novel insights into the pathogenesis of parasite-associated epilepsy. We compare the clinical and electrophysiological findings in epilepsy associated with these highly prevalent parasites and discuss the mechanisms involved in epileptogenesis.
RECENT FINDINGS
Electrophysiological and imaging biomarkers continue to emerge, and individuals who are at-risk of developing parasite-associated epilepsies are being identified with greater reliability. While both Taenia solium and Plasmodium falciparum directly affect the brain parenchyma, Onchocerca volvulus is not known to invade the central nervous system. Thus, the causal association between O. volvulus and epilepsy remains controversial. Both NCC and CM have a well-defined acute phase when the parasites directly or indirectly invade the brain parenchyma and lead to local inflammatory changes. This is followed by a chronic phase marked by recurrent seizures. However, these stages of epileptogenic process have not been identified in the case of O. volvulus.
Topics: Epilepsy; Humans; Intestinal Volvulus; Neurocysticercosis; Parasitic Diseases; Reproducibility of Results
PubMed: 35332514
DOI: 10.1007/s11910-022-01187-6 -
Annual Review of Pathology Jan 2020Nodding syndrome is a rare, enigmatic form of pediatric epilepsy that has occurred in an epidemic fashion beginning in the early 2000s in geographically distinct regions... (Review)
Review
Nodding syndrome is a rare, enigmatic form of pediatric epilepsy that has occurred in an epidemic fashion beginning in the early 2000s in geographically distinct regions of Africa. Despite extensive investigation, the etiology of nodding syndrome remains unclear, although much progress has been made in understanding the pathogenesis of the disease, as well as in treatment and prevention. Nodding syndrome is recognized as a defined disease entity, but it is likely one manifestation along a continuum of -associated neurological complications. This review examines the epidemiology of nodding syndrome and its association with environmental factors. It provides a critical analysis of the data that support or contradict the leading hypotheses of the etiologies underlying the pathogenesis of the syndrome. It also highlights the important progress made in treating and preventing this devastating neurological disease and prioritizes important areas for future research.
Topics: Africa; Animals; Child; Epilepsy; Humans; Nodding Syndrome; Onchocerca volvulus; Onchocerciasis
PubMed: 31977293
DOI: 10.1146/annurev-pathmechdis-012419-032748 -
Research and Reports in Tropical... 2020Onchocerciasis is a parasitic infection caused by the filarial nematode and transmitted through the bites of black flies of the genus that breed in rivers and streams.... (Review)
Review
Onchocerciasis is a parasitic infection caused by the filarial nematode and transmitted through the bites of black flies of the genus that breed in rivers and streams. The impact of mass treatment with ivermectin and supplemented by vector control in some countries has changed the global scene of onchocerciasis. There has been reported progress made in elimination of onchocerciasis in central and southern American countries and in some localities in Africa. The target for elimination in the Americas has been set at 2022 while for 12 countries in Africa this is expected in 2030. This review was conducted to examine the current status of onchocerciasis elimination at the global level and report on progress made. Literature searches were made through PubMed, articles in English or English abstracts, reports and any other relevant articles related to the subject. The global burden of onchocerciasis is progressively reducing and is no longer a public health problem in some regions. However, programs are challenged with a range of issues: cross-border transmission, diagnostic tools, co-endemicity, limited workforce in entomology and maintaining enthusiasm among community drug distributors. More concerted effort using appropriate tools is required to overcome the challenges.
PubMed: 33117052
DOI: 10.2147/RRTM.S224364 -
International Journal of Infectious... Mar 2021Nodding syndrome is one of several forms of onchocerciasis-associated epilepsy (OAE) seen among children in areas formerly hyperendemic for the transmission of... (Review)
Review
Nodding syndrome is one of several forms of onchocerciasis-associated epilepsy (OAE) seen among children in areas formerly hyperendemic for the transmission of Onchocerca volvulus. These forms of epilepsy are highly prevalent and clustered in certain villages located close to blackfly (Diptera: Simuliidae) breeding sites. OAE presents with a wide spectrum of seizures, including generalized tonic-clonic and head nodding seizures, impaired cognitive function, growth stunting and delayed puberty. In 2014, the present authors published a perspective paper in this journal which hypothesized that nodding syndrome may be caused by either a neurotropic virus transmitted by blackflies or an endosymbiont present within the O. volvulus parasite. Seven years later, this critical review presents progress in nodding syndrome research, and assesses whether it is still plausible that a neurotropic virus or endosymbiont could be the cause.
Topics: Animals; Biomedical Research; Humans; Nodding Syndrome; Onchocerca volvulus; Onchocerciasis; Prevalence
PubMed: 33556614
DOI: 10.1016/j.ijid.2021.02.006 -
PLoS Neglected Tropical Diseases Jan 2021The possibility that onchocerciasis may cause epilepsy has been suggested for a long time, but thus far, an etiological link has not been universally accepted. The... (Review)
Review
BACKGROUND
The possibility that onchocerciasis may cause epilepsy has been suggested for a long time, but thus far, an etiological link has not been universally accepted. The objective of this review is to critically appraise the relationship between Onchocerca volvulus and epilepsy and subsequently apply the Bradford Hill criteria to further evaluate the likelihood of a causal association.
METHODS
PubMed and gray literature published until September 15, 2020, were searched and findings from original research were synthesized. Adherence to the 9 Bradford Hill criteria in the context of onchocerciasis and epilepsy was determined to assess whether the criteria are met to strengthen the evidence base for a causal link between infection with O. volvulus and epilepsy, including the nodding syndrome.
RESULTS
Onchocerciasis as a risk factor for epilepsy meets the following Bradford Hill criteria for causality: strength of the association, consistency, temporality, and biological gradient. There is weaker evidence supporting causality based on the specificity, plausibility, coherence, and analogy criteria. There is little experimental evidence. Considering the Bradford Hill criteria, available data suggest that under certain conditions (high microfilarial load, timing of infection, and perhaps genetic predisposition), onchocerciasis is likely to cause epilepsy including nodding and Nakalanga syndromes.
CONCLUSION
Applying the Bradford Hill criteria suggests consistent epidemiological evidence that O. volvulus infection is a trigger of epilepsy. However, the pathophysiological mechanisms responsible for seizure induction still need to be elucidated.
Topics: Animals; Causality; Child; Databases, Factual; Epilepsy; Humans; Microfilariae; Nodding Syndrome; Onchocerca volvulus; Onchocerciasis; Risk Factors; Seizures
PubMed: 33411705
DOI: 10.1371/journal.pntd.0008965 -
Trends in Parasitology Feb 2023Onchocerciasis-associated epilepsy (OAE) is an important neglected public health problem in areas with high ongoing onchocerciasis transmission. The risk that children... (Review)
Review
Onchocerciasis-associated epilepsy (OAE) is an important neglected public health problem in areas with high ongoing onchocerciasis transmission. The risk that children in such areas develop epilepsy is related to their Onchocerca volvulus microfilarial (mf) load. Before the implementation of mass treatment with ivermectin, microfilariae were detected in cerebrospinal fluid (CSF). More recently, neither O. volvulus microfilariae nor DNA were detected in CSF or brain tissue; however, these samples were obtained years after seizure onset. It is possible that during fever-induced increased blood-brain barrier permeability, microfilariae enter the brain and, upon dying, cause an inflammatory reaction inducing seizures. Including OAE in the onchocerciasis disease burden estimation may mobilise extra resources for onchocerciasis disease elimination and treatment/care of OAE-affected persons/families.
Topics: Child; Animals; Humans; Onchocerciasis; Onchocerca volvulus; Epilepsy; Ivermectin; Seizures; Microfilariae
PubMed: 36528471
DOI: 10.1016/j.pt.2022.11.010 -
Current Research in Parasitology &... 2022Identifying the molecular mechanisms controlling the host's response to infection with is important to understand how the human host controls such parasitic infection....
Identifying the molecular mechanisms controlling the host's response to infection with is important to understand how the human host controls such parasitic infection. Little is known of the cellular immune response upon infection with . We performed a transcriptomic study using PAXgene-preserved whole blood from 30 nodule-positive individuals and 21 non-endemic controls. It was found that of the 45,042 transcripts that were mapped to the human genome, 544 were found to be upregulated and 447 to be downregulated in nodule-positive individuals (adjusted -value < 0.05). Pathway analysis was performed on this set of differentially expressed genes, which demonstrated an impact on oxidative phosphorylation and protein translation. Upstream regulator analysis showed that the mTOR associated protein RICTOR appears to play an important role in inducing the transcriptional changes in infected individuals. Functional analysis of the genes affected by infection indicated a suppression of antibody response, Th17 immune response and proliferation of activated T lymphocytes. Multiple regression models were used to select 22 genes that could contribute significantly in the generation of a classifier to predict infection with . For these 22 genes, as well as for 8 reference target genes, validated RT-qPCR assays were developed and used to re-analyze the discovery sample set. These data were used to perform elastic net regularized logistic regression and a panel of 7 genes was found to be the best performing classifier. The resulting algorithm returns a value between 0 and 1, reflecting the predicted probability of being infected. A validation panel of 69 nodule-positive individuals and 5 non-endemic controls was used to validate the performance of this classifier. Based on this validation set only, a sensitivity of 94.2% and a specificity of 60.0% was obtained. When combining the discovery test set and validation set, a sensitivity of 96.0% and a specificity of 92.3% was obtained. Large-scale validation approaches will be necessary to define the intended use for this classifier. Besides the use as marker for infection in MDA efficacy surveys and epidemiological transmission studies, this classifier might also hold potential as pharmacodynamic marker in macrofilaricide clinical trials.
PubMed: 36082138
DOI: 10.1016/j.crpvbd.2022.100100 -
Parasites & Vectors Jan 2021The control of onchocerciasis in Ghana started in 1974 under the auspices of the Onchocerciasis Control Programme (OCP). Between 1974 and 2002, a combination of... (Review)
Review
BACKGROUND
The control of onchocerciasis in Ghana started in 1974 under the auspices of the Onchocerciasis Control Programme (OCP). Between 1974 and 2002, a combination of approaches including vector control, mobile community ivermectin treatment, and community-directed treatment with ivermectin (CDTI) were employed. From 1997, CDTI became the main control strategy employed by the Ghana OCP (GOCP). This review was undertaken to assess the impact of the control interventions on onchocerciasis in Ghana between 1974 and 2016, since which time the focus has changed from control to elimination.
METHODS
In this paper, we review programme data from 1974 to 2016 to assess the impact of control activities on prevalence indicators of onchocerciasis. This review includes an evaluation of CDTI implementation, microfilaria (Mf) prevalence assessments and rapid epidemiological mapping of onchocerciasis results.
RESULTS
This review indicates that the control of onchocerciasis in Ghana has been very successful, with a significant decrease in the prevalence of infection from 69.13% [95% confidence interval) CI 60.24-78.01] in 1975 to 0.72% (95% CI 0.19-1.26) in 2015. Similarly, the mean community Mf load decreased from 14.48 MF/skin snip in 1975 to 0.07 MF/skin snip (95% CI 0.00-0.19) in 2015. Between 1997 and 2016, the therapeutic coverage increased from 58.50 to 83.80%, with nearly 100 million ivermectin tablets distributed.
CONCLUSIONS
Despite the significant reduction in the prevalence of onchocerciasis in Ghana, there are still communities with MF prevalence above 1%. As the focus of the GOCP has changed from the control of onchocerciasis to its elimination, both guidance and financial support are required to ensure that the latter goal is met.
Topics: Animals; Communicable Disease Control; Ghana; Humans; Ivermectin; Onchocerca volvulus; Onchocerciasis; Prevalence
PubMed: 33388081
DOI: 10.1186/s13071-020-04507-2 -
The British Journal of Dermatology Feb 2021Onchocerciasis is a neglected tropical disease caused by a nematode parasite, Onchocerca volvulus, and transmitted by bites of Simulium blackflies which breed near... (Review)
Review
Onchocerciasis is a neglected tropical disease caused by a nematode parasite, Onchocerca volvulus, and transmitted by bites of Simulium blackflies which breed near fast-flowing rivers. In humans, thousands of microfilariae (immature worms) migrate to the skin and eyes where they cause pathology. Historically, much research was devoted to the serious effect of blindness, from which the disease earns its alternative name of 'river blindness'. Mapping the burden of onchocercal skin disease (OSD) was expedited by the development of a clinical classification and grading system that facilitated comparison of data from different countries. After successful field testing in Nigeria, the classification scheme was used in a multicountry study in seven endemic sites, to estimate the true burden of OSD across Africa. High levels of OSD were found, affecting 28% of the population. A new control programme, the African Programme for Onchocerciasis Control (APOC) was launched in 20 countries using annual doses of ivermectin, donated by Merck & Co., Inc. The multicountry study also found a close correlation between the levels of itching and OSD with the level of endemicity, as determined by the prevalence of onchocercal nodules. This enabled APOC to use Rapid Epidemiological Mapping of Onchocerciasis, which entailed identifying likely vector breeding sites near rivers, then sampling 50 adult males in nearby villages to determine the prevalence of nodules and delineate which villages required treatment. Onchocerciasis is now targeted for elimination in Africa, and the challenge is to complete Onchocerciasis Elimination Mapping of hypoendemic areas using serology.
Topics: Adult; Animals; Humans; Ivermectin; Male; Neglected Diseases; Nigeria; Onchocerciasis; Prevalence
PubMed: 32302410
DOI: 10.1111/bjd.19143