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PLoS Neglected Tropical Diseases May 2024
Topics: Onchocerca volvulus; Humans; Animals; Onchocerciasis; Nodding Syndrome; Epilepsy
PubMed: 38722927
DOI: 10.1371/journal.pntd.0012076 -
Pathogens (Basel, Switzerland) Jul 2023Onchocerciasis is a neglected tropical disease targeted for elimination using ivermectin mass administration. Ivermectin kills the microfilariae and temporarily arrests...
Onchocerciasis is a neglected tropical disease targeted for elimination using ivermectin mass administration. Ivermectin kills the microfilariae and temporarily arrests microfilariae production by the macrofilariae. We genotyped 436 microfilariae from 10 people each in Ituri, Democratic Republic of the Congo (DRC), and Maridi County, South Sudan, collected before and 4-5 months after ivermectin treatment. Population genetic analyses identified 52 and 103 mitochondrial DNA haplotypes among the microfilariae from DRC and South Sudan, respectively, with few haplotypes shared between people. The percentage of genotype-based correct assignment to person within DRC was ~88% and within South Sudan ~64%. Rarefaction and extrapolation analysis showed that the genetic diversity in DRC, and even more so in South Sudan, was captured incompletely. The results indicate that the per-person adult worm burden is likely higher in South Sudan than DRC. Analyses of haplotype data from a subsample ( = 4) did not discriminate genetically between pre- and post-treatment microfilariae, confirming that post-treatment microfilariae are not the result of new infections. With appropriate sampling, mitochondrial haplotype analysis could help monitor changes in the number of macrofilariae in a population as a result of treatment, identify cases of potential treatment failure, and detect new infections as an indicator of continuing transmission.
PubMed: 37513818
DOI: 10.3390/pathogens12070971 -
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 -
F1000Research 2023A high prevalence of onchocerciasis-associated epilepsy (OAE) has been observed in onchocerciasis-endemic areas with high ongoing transmission. However, the...
BACKGROUND
A high prevalence of onchocerciasis-associated epilepsy (OAE) has been observed in onchocerciasis-endemic areas with high ongoing transmission. However, the pathogenesis of OAE remains to be elucidated. We hypothesise that the virome could be involved in inducing epilepsy. With this study, we aim to describe the virome and identify potential neurotropic viruses linked to OAE.
METHODS
In Maridi County, an onchocerciasis endemic area in South Sudan with a high prevalence of OAE, we will conduct an exploratory case-control study enrolling 40 persons aged 12 years and above with palpable onchocerciasis nodules. Cases will be participants with OAE (n=20), who will be age- and village-matched with controls without epilepsy (n=20). For each study participant, two skin snips at the iliac crest will be obtained to collect microfilariae, and one nodulectomy will be performed to obtain adult worms. A viral metagenomic study will be conducted on microfilariae and adult worms, and the virome of persons with and without OAE will be compared. The number, size, and localisation of onchocerciasis nodules in persons with and without OAE will be described. Moreover, the pre- and post-nodulectomy frequency of seizures in persons with OAE will be compared.
ETHICS AND DISSEMINATION
The protocol has been approved by the Ethics Committee of the University of Antwerp and the Ministry of Health of South Sudan. Findings will be disseminated nationally and internationally via meetings and peer-reviewed publications.
REGISTRATION
ClinicalTrials.gov registration NCT05868551 ( https://clinicaltrials.gov/study/NCT05868551).
PROTOCOL VERSION
1.1, dated 09/05/2023.
Topics: Adult; Animals; Humans; Onchocerciasis; Onchocerca volvulus; Case-Control Studies; Intestinal Volvulus; Epilepsy; Microfilariae
PubMed: 38439783
DOI: 10.12688/f1000research.138774.1 -
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 -
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 -
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 -
Parasites & Vectors Mar 2024After ivermectin became available, diethylcarbamazine (DEC) use was discontinued because of severe adverse reactions, including ocular reactions, in individuals with... (Randomized Controlled Trial)
Randomized Controlled Trial
Onchocerca volvulus microfilariae in the anterior chambers of the eye and ocular adverse events after a single dose of 8 mg moxidectin or 150 µg/kg ivermectin: results of a randomized double-blind Phase 3 trial in the Democratic Republic of the Congo, Ghana and Liberia.
BACKGROUND
After ivermectin became available, diethylcarbamazine (DEC) use was discontinued because of severe adverse reactions, including ocular reactions, in individuals with high Onchocerca volvulus microfilaridermia (microfilariae/mg skin, SmfD). Assuming long-term ivermectin use led to < 5 SmfD with little or no eye involvement, DEC + ivermectin + albendazole treatment a few months after ivermectin was proposed. In 2018, the US FDA approved moxidectin for treatment of O. volvulus infection. The Phase 3 study evaluated SmfD, microfilariae in the anterior chamber (mfAC) and adverse events (AEs) in ivermectin-naïve individuals with ≥ 10 SmfD after 8 mg moxidectin (n = 978) or 150 µg/kg ivermectin (n = 494) treatment.
METHODS
We analyzed the data from 1463 participants with both eyes evaluated using six (0, 1-5, 6-10, 11-20, 21-40, > 40) mfAC and three pre-treatment (< 20, 20 to < 50, ≥ 50) and post-treatment (0, > 0-5, > 5) SmfD categories. A linear mixed model evaluated factors and covariates impacting mfAC levels. Ocular AEs were summarized by type and start post-treatment. Logistic models evaluated factors and covariates impacting the risk for ocular AEs.
RESULTS
Moxidectin and ivermectin had the same effect on mfAC levels. These increased from pre-treatment to Day 4 and Month 1 in 20% and 16% of participants, respectively. Six and 12 months post-treatment, mfAC were detected in ≈5% and ≈3% of participants, respectively. Ocular Mazzotti reactions occurred in 12.4% of moxidectin- and 10.2% of ivermectin-treated participants without difference in type or severity. The risk for ≥ 1 ocular Mazzotti reaction increased for women (OR 1.537, 95% CI 1.096-2.157) and with mfAC levels pre- and 4 days post-treatment (OR 0: > 10 mfAC 2.704, 95% CI 1.27-5.749 and 1.619, 95% CI 0.80-3.280, respectively).
CONCLUSIONS
The impact of SmfD and mfAC levels before and early after treatment on ocular AEs needs to be better understood before making decisions on the risk-benefit of strategies including DEC. Such decisions should take into account interindividual variability in SmfD, mfAC levels and treatment response and risks to even a small percentage of individuals.
Topics: Animals; Female; Humans; Anterior Chamber; Democratic Republic of the Congo; Double-Blind Method; Ghana; Intestinal Volvulus; Ivermectin; Liberia; Macrolides; Microfilariae; Onchocerca; Onchocerca volvulus; Onchocerciasis; Male
PubMed: 38491528
DOI: 10.1186/s13071-023-06087-3 -
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 -
Pathogens (Basel, Switzerland) Mar 2024Despite several decades of mass drug administration and elimination-related activities, human onchocerciasis still represents a major parasitic threat in endemic...
Despite several decades of mass drug administration and elimination-related activities, human onchocerciasis still represents a major parasitic threat in endemic regions. Among the challenges encountered by the elimination program is the lack of a suitable diagnostic tool that is accurate and non-invasive. Currently used methods are either invasive or not suitable for monitoring large numbers of patients. Herein, we describe the identification and characterization of heat shock protein 70 (HSP70) as a novel diagnostic biomarker for human onchocerciasis, which can directly be detected in urine samples of infected patients. This nematode-specific antigen was identified through LC-MS after differential SDS-PAGE using urine-derived protein extracts from -infected patients in Cameroon. Polyclonal antibodies generated in rabbits after cloning and expression of HSP70 in reliably differentiated between urine samples from infected- and uninfected patients in a hypoendemic area of human onchocerciasis. These results provide an excellent basis for further development of a non-invasive and scalable diagnostic assay for human onchocerciasis using urine samples. Such a urine-based diagnostic assay will be of major importance for the elimination program of human onchcerciasis in endemic countries.
PubMed: 38668248
DOI: 10.3390/pathogens13040293