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Brain Communications 2023Nodding syndrome is a paediatric epileptic encephalopathy of unknown aetiology that affects children in impoverished communities of Eastern Africa subject to internal...
Nodding syndrome is a paediatric epileptic encephalopathy of unknown aetiology that affects children in impoverished communities of Eastern Africa subject to internal displacement. Set in southcentral South Sudan, where nodding syndrome first surfaced circa 1990, an important new study of recent-onset cases of nodding syndrome examined parasitic, bacterial, viral, immune-mediated, metabolic and nutritional factors associated with the brain disease. Infection with the nematode , but not with , was the most prominent finding in nodding syndrome cases versus controls. While is unlikely to be causal of nodding syndrome, investigation of the freshwater habitats, where insect-to-human transmission of the filarial larvae takes place, may reveal a clue as to the aetiology of this neurodegenerative disease. The culpable environmental agent(s) must be able to induce neuroinflammation and tau pathology preferentially in infants and children.
PubMed: 37731902
DOI: 10.1093/braincomms/fcad236 -
The American Journal of Tropical... Oct 2023Lymphatic filariasis (LF) and onchocerciasis (OV) are among the neglected tropical diseases (NTD) targeted for elimination in Ethiopia. We used a transmission assessment...
Lymphatic filariasis (LF) and onchocerciasis (OV) are among the neglected tropical diseases (NTD) targeted for elimination in Ethiopia. We used a transmission assessment survey (TAS-1) to evaluate the serological status of OV in three co-endemic districts in Gambella simultaneously. During May and June 2019, blood samples were collected from 6- to 7-year-old children who were randomly selected through standard community-based TAS methodology. Children were tested for both circulating filarial antigen (CFA) for LF via filariasis test strip and for Onchocerca volvulus 16 (Ov16) antibody for OV via laboratory-based ELISA. A total of 3,377 children from 150 villages in the three districts were tested; 1,823 (54.0%) were male. All three districts had CFA results below the critical threshold for stopping LF mass drug administration (MDA). In contrast, 40 children (1.2%) were positive for Ov16 antibody, well above the WHO's OV stop MDA threshold of 0.1%. The integrated assessment indicated two programmatic decisions: stop MDA for LF and continue MDA for OV. Accordingly, albendazole MDA was discontinued in the districts but ivermectin MDA continued. This integrated assessment showed that a random sample for TAS can give important information about OV transmission status in co-endemic areas.
Topics: Child; Animals; Humans; Male; Female; Wuchereria bancrofti; Onchocerca volvulus; Prevalence; Ethiopia; Elephantiasis, Filarial; Ivermectin; Albendazole; Antigens, Helminth; Neglected Diseases
PubMed: 37696513
DOI: 10.4269/ajtmh.22-0392 -
Scientific Reports Sep 2023Black flies are blood-sucking insects of public health importance, and they are effective vectors of pathogens and parasites, such as filarial nematodes of the genus...
Black flies are blood-sucking insects of public health importance, and they are effective vectors of pathogens and parasites, such as filarial nematodes of the genus Onchocerca. Our previous surveys have shown that individuals of Simulium turgaicum are annoying pests of humans and livestock in the Aras River Basin of Iran. In the present study, adult black flies of S. turgaicum were trapped from different ecotopes of five villages in Khoda-Afarin County, Iran. By using a sensitive nested PCR assay and targeting the nuclear 18S rDNA-ITS1 marker, filarial infections were found in 38 (1.89%) of 2005 black flies. Homology exploration of 360 bp of the sequences indicated that the filarial worms are members of the family Onchocercidae, with maximum alignment scores of 93-95%. Phylogenetic analysis showed that two Iranian Onchocerca isolates were clustered in the O. fasciata-O. volvulus lineage and were well separated from other filarial nematodes. Both the entomological evidence (empty abdomen of the specimens) and climatologic data (adequate accumulated degree days for development) suggest that the filarial DNA was probably that of infective larvae of vertebrates. This is the first report of an infection by Onchocerca species in S. turgaicum and the first record of onchocercids in black flies in Iran; however, more research is required to demonstrate transmission of these filarial worms by black flies in nature.
Topics: Adult; Animals; Humans; Simuliidae; Onchocerca; Iran; Phylogeny; Larva
PubMed: 37666968
DOI: 10.1038/s41598-023-41890-z -
International Journal For Parasitology Feb 2024The heartworm, Dirofilaria immitis, is a filarial parasitic nematode responsible for significant morbidity and mortality in wild and domesticated canids. Resistance to...
The heartworm, Dirofilaria immitis, is a filarial parasitic nematode responsible for significant morbidity and mortality in wild and domesticated canids. Resistance to macrocyclic lactone drug prevention represents a significant threat to parasite control and has prompted investigations to understand the genetic determinants of resistance. This study aimed to improve the genomic resources of D. immitis to enable a more precise understanding of how genetic variation is distributed within and between parasite populations worldwide, which will inform the likelihood and rate by which parasites, and in turn, resistant alleles, might spread. We have guided the scaffolding of a recently published genome assembly for D. immitis (ICBAS_JMDir_1.0) using the chromosomal-scale reference genomes of Brugia malayi and Onchocerca volvulus, resulting in an 89.5 Mb assembly composed of four autosomal- and one sex-linked chromosomal-scale scaffolds representing 99.7% of the genome. Publicly available and new whole-genome sequencing data from 32 D. immitis samples from Australia, Italy and the USA were assessed using principal component analysis, nucleotide diversity (Pi) and absolute genetic divergence (Dxy) to characterise the global genetic structure and measure within- and between-population diversity. These population genetic analyses revealed broad-scale genetic structure among globally diverse samples and differences in genetic diversity between populations; however, fine-scale subpopulation analysis was limited and biased by differences between sample types. Finally, we mapped single nucleotide polymorphisms previously associated with macrocyclic lactone resistance in the new genome assembly, revealing the physical linkage of high-priority variants on chromosome 3, and determined their frequency in the studied populations. This new chromosomal assembly for D. immitis now allows for a more precise investigation of selection on genome-wide genetic variation and will enhance our understanding of parasite transmission and the spread of genetic variants responsible for resistance to treatment.
Topics: Dogs; Animals; Dirofilaria immitis; Metagenomics; Genome, Helminth; Lactones; Australia; Dirofilariasis; Dog Diseases
PubMed: 37652224
DOI: 10.1016/j.ijpara.2023.07.006 -
Biochemistry and Biophysics Reports Sep 2023Nodding syndrome is a neurological disease of children in northern Uganda. Infection with the nematode parasite has been epidemiologically implicated as the cause of...
Nodding syndrome is a neurological disease of children in northern Uganda. Infection with the nematode parasite has been epidemiologically implicated as the cause of the disease. It has been proposed that an autoantibody directed against the human protein leiomodin-1 cross reacts with a tropomyosin-like nematode protein, thus suggesting that nodding syndrome is an autoimmune brain disease due to extra-cerebral parasitism. This hypothesis is dependent on constitutive neuronal expression of leiomodin-1. We tested this hypothesis by studying the distribution of leiomodin-1 in the normal human brain and other human tissues using immunohistochemistry. We found that immunostaining for leiomodin-1 follows a smooth muscle cell specific pattern. In the brain, it is confined to the smooth muscle cells of cerebral blood vessels and is not generally present in neurons or glia. However, immunoreactivity was identified in human Purkinje cell membrane and the body wall of (as a proxy for ) but only when immunostained with an antibody recognizing the N-terminal of leiomodin-1. Homology between leiomodin-1 and tropomodulin, specifically at the N-terminus, could explain why leiomodin-1 antibody cross reactivity between human Purkinje cells and . However, we cannot provide proof confirming that the immunoreactivity in the membranes of Purkinje cells is specifically caused by the expression of tropomodulin. To overcome this limitation, further investigations using additional immunohistochemical and biochemical studies are required to corroborate our findings and provide more comprehensive evidence. Nevertheless, our findings do not support to the autoimmunity hypothesis involving and leiomodin-1. To gain a more comprehensive understanding of the cause and pathogenesis of NS, it is essential to explore alternative hypotheses.
PubMed: 37601452
DOI: 10.1016/j.bbrep.2023.101498 -
Philosophical Transactions of the Royal... Oct 2023Epidemiological and modelling studies suggest that elimination of transmission (EoT) throughout Africa may not be achievable with annual mass drug administration (MDA)...
Epidemiological and modelling studies suggest that elimination of transmission (EoT) throughout Africa may not be achievable with annual mass drug administration (MDA) of ivermectin alone, particularly in areas of high endemicity and vector density. Single-dose Phase II and III clinical trials demonstrated moxidectin's superiority over ivermectin for prolonged clearance of microfilariae. We used the stochastic, individual-based EPIONCHO-IBM model to compare the probabilities of reaching EoT between ivermectin and moxidectin MDA for a range of endemicity levels (30 to 70% baseline microfilarial prevalence), treatment frequencies (annual and biannual) and therapeutic coverage/adherence values (65 and 80% of total population, with, respectively, 5 and 1% of systematic non-adherence). EPIONCHO-IBM's projections indicate that biannual (six-monthly) moxidectin MDA can reduce by half the number of years necessary to achieve EoT in mesoendemic areas and might be the only strategy that can achieve EoT in hyperendemic areas. Data needed to improve modelling projections include (i) the effect of repeated annual and biannual moxidectin treatment; (ii) inter- and intra-individual variation in response to successive treatments with moxidectin or ivermectin; (iii) the effect of moxidectin and ivermectin treatment on L3 development into adult worms; and (iv) patterns of adherence to moxidectin and ivermectin MDA. This article is part of the theme issue 'Challenges in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs'.
Topics: Humans; Onchocerciasis; Ivermectin; Mass Drug Administration; Africa; Neglected Diseases
PubMed: 37598705
DOI: 10.1098/rstb.2022.0277 -
PLoS Neglected Tropical Diseases Aug 2023Nodding syndrome (NS) is a phenotypic presentation of onchocerciasis-associated epilepsy (OAE). OAE is an important public health problem in areas with high ongoing...
Nodding syndrome (NS) is a phenotypic presentation of onchocerciasis-associated epilepsy (OAE). OAE is an important public health problem in areas with high ongoing Onchocerca volvulus transmission. OAE, including NS, is preventable by strengthening onchocerciasis elimination programs. The presence of tau in OAE postmortem brains could be the consequence of neuroinflammation directly or indirectly induced by O. volvulus. Omics research is needed to investigate whether O. volvulus worms contain a neurotropic virus.
Topics: Onchocerciasis; Nodding Syndrome; Onchocerca volvulus; Humans
PubMed: 37590176
DOI: 10.1371/journal.pntd.0011523 -
Infectious Diseases of Poverty Aug 2023In onchocerciasis-endemic areas with high ongoing Onchocerca volvulus transmission, a high prevalence of epilepsy has been reported. This study aimed to determine the...
BACKGROUND
In onchocerciasis-endemic areas with high ongoing Onchocerca volvulus transmission, a high prevalence of epilepsy has been reported. This study aimed to determine the prevalence and clinical characteristics of epilepsy in the Bono Region of Ghana following 27 years of implementation of ivermectin mass drug administration (MDA).
METHODS
Between October 2020 and August 2021, cross-sectional surveys were conducted in nine communities in the Tain District and Wenchi Municipality of the Bono Region of Ghana. In the first stage, a random door-to-door approach was used to screen the population for epilepsy using a pre-tested questionnaire. Persons suspected of having epilepsy were invited for a second-stage neurological examination for case verification. Community O. volvulus microfilarial infection status and Ov16 seropositivity were also determined. Ninety-five confidence intervals (95% CI) for prevalence values were calculated using the Wilson Score Interval.
RESULTS
Of the 971 participants, 500 (51.5%) were females, and the median age (interquartile range) was 26 (15‒43) years. Fourteen participants (1.4%, 95% CI: 1.0‒2.0) were diagnosed as having epilepsy with generalized seizures being the most frequent seizure type (85.7%, 12/14). The overall microfilarial prevalence of O. volvulus was 10.3% (November 2020) and 9.9% (August 2021); the Ov16 seroprevalence was 22.2% (June 2021). Only 63.2% took ivermectin in the last round of MDA distribution in March 2021.
CONCLUSIONS
The 1.4% prevalence of epilepsy in the Bono region is similar to the median epilepsy prevalence in sub-Saharan Africa. However, the persistent microfilarial prevalence and low ivermectin study coverage call for the Ghana Onchocerciasis Elimination Programme to step up its efforts to ensure that the gains achieved are consolidated and improved to achieve the elimination of onchocerciasis by 2030.
Topics: Female; Animals; Humans; Adult; Male; Ivermectin; Onchocerciasis; Cross-Sectional Studies; Ghana; Intestinal Volvulus; Mass Drug Administration; Prevalence; Seroepidemiologic Studies; Epilepsy; Microfilariae
PubMed: 37587500
DOI: 10.1186/s40249-023-01117-9 -
PLoS Neglected Tropical Diseases Aug 2023Previous studies have described the association of onchocerciasis (caused by Onchocerca volvulus) with epilepsy, including nodding syndrome, although a clear etiological...
Previous studies have described the association of onchocerciasis (caused by Onchocerca volvulus) with epilepsy, including nodding syndrome, although a clear etiological link is still missing. Cases are found in different African countries (Tanzania, South Sudan, Uganda, Democratic Republic of the Congo, Central African Republic and Cameroon). In our study we investigated immunological parameters (cytokine, chemokine, immunoglobulin levels) in individuals from the Mahenge area, Tanzania, presenting with either epilepsy or nodding syndrome with or without O. volvulus infection and compared them to O. volvulus negative individuals from the same endemic area lacking neurological disorders. Additionally, cell differentiation was performed using blood smears and systemic levels of neurodegeneration markers, leiomodin-1 and N-acetyltyramine-O, β-glucuronide (NATOG) were determined. Our findings revealed that cytokines, most chemokines and neurodegeneration markers were comparable between both groups presenting with epilepsy or nodding syndrome. However, we observed elevated eosinophil percentages within the O. volvulus positive epilepsy/nodding syndrome patients accompanied with increased eosinophilic cationic protein (ECP) and antigen-specific IgG levels in comparison to those without an O. volvulus infection. Furthermore, highest levels of NATOG were found in O. volvulus positive nodding syndrome patients. These findings highlight that the detection of distinct biomarkers might be useful for a differential diagnosis of epilepsy and nodding syndrome in O. volvulus endemic areas. Trial-registration: NCT03653975.
Topics: Animals; Humans; Onchocerciasis; Onchocerca volvulus; Nodding Syndrome; Intestinal Volvulus; Epilepsy; Uganda; Cytokines
PubMed: 37535695
DOI: 10.1371/journal.pntd.0011503