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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 -
International Health Mar 2018In the past few years, efforts to eliminate onchocerciasis from Africa have intensified. These efforts are primarily based on the mass distribution of the... (Review)
Review
In the past few years, efforts to eliminate onchocerciasis from Africa have intensified. These efforts are primarily based on the mass distribution of the anti-helminthic drug Mectizan™ (ivermectin). This program has led to the development of new guidelines by the World Health Organization for the verification that transmission has been suppressed and eventually eliminated. The requirements of diagnostic tools for this purpose differ in many ways from tests used to diagnose infection in individuals. In this review, we summarize the progress that has been made to identify diagnostics that meet the specialized requirements needed to verify onchocerciasis elimination, discuss why these tests were selected and summarize the needs that still exist to complete the arsenal of diagnostic tools that will be useful as the goal of elimination is achieved.
Topics: Africa; Animals; Antiparasitic Agents; Disease Eradication; Humans; Ivermectin; Onchocerca volvulus; Onchocerciasis
PubMed: 29471336
DOI: 10.1093/inthealth/ihx047 -
PLoS Neglected Tropical Diseases Mar 2018Onchocerciasis in Yemen is one of the most neglected diseases, where baseline estimates of onchocerciasis and monitoring of the impact of ivermectin regularly...
Onchocerca volvulus infection in Tihama region - west of Yemen: Continuing transmission in ivermectin-targeted endemic foci and unveiled endemicity in districts with previously unknown status.
BACKGROUND
Onchocerciasis in Yemen is one of the most neglected diseases, where baseline estimates of onchocerciasis and monitoring of the impact of ivermectin regularly administered to the affected individuals on its transmission are lacking. Therefore, this study aimed to determine the anti-Ov16 IgG4 seroprevalence among local communities of Hodeidah and Al-Mahwit governorates of Tihama region. The factors possibly associated with previous exposure to infection were also studied.
METHODOLOGY/PRINCIPAL FINDINGS
This cross-sectional study was conducted in two ivermectin-targeted districts endemic for onchocerciasis in Hodeidah and Al-Mahwit and two untargeted districts with unknown previous endemicity in Hodeidah between February and July 2017. For 508 residents sampled by a multi-stage random approach, data were collected and blood specimens were screened for anti-Ov16 IgG4 using the SD BIOLINE Onchocerciasis IgG4 rapid tests. The study revealed an overall anti-Ov16 IgG4 rate of 18.5% (94/508) in all surveyed districts, with 10.2% (12/118) of children aged ≤10 years being seropositive. Moreover, rates of 8.0% (4/50) and 6.1% (4/66) were found in districts not officially listed as endemic for the disease. Multivariable analysis confirmed the age of more than ten years and residing within a large family as the independent predictors of exposure to infection.
CONCLUSIONS/SIGNIFICANCE
Onchocerciasis transmission is still ongoing as supported by the higher anti-Ov16 IgG4 seroprevalence rate among children aged ≤10 years compared to that (<0.1%) previously set by the World Health Organization as a serologic criterion for transmission interruption. Further large-scale studies combining serologic and entomologic criteria are recommended for the mapping of O. volvulus in human and blackfly populations in endemic foci and their neighboring areas of uncertain endemicity. In addition, ivermectin distribution, coverage and impact on disease transmission need to be continually assessed.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Animals; Antibodies, Helminth; Child; Child, Preschool; Cross-Sectional Studies; Endemic Diseases; Female; Humans; Immunoglobulin G; Infant; Infant, Newborn; Insect Vectors; Ivermectin; Male; Middle Aged; Multivariate Analysis; Onchocerca volvulus; Onchocerciasis; Seroepidemiologic Studies; Simuliidae; Yemen; Young Adult
PubMed: 29505580
DOI: 10.1371/journal.pntd.0006329 -
The American Journal of Tropical... Dec 2015
Topics: Animals; Disease Eradication; Elephantiasis, Filarial; Female; Humans; Male; Onchocerca volvulus; Onchocerciasis
PubMed: 26503272
DOI: 10.4269/ajtmh.15-0688 -
Epilepsia Open Jun 2021Nodding syndrome is a poorly understood epileptic encephalopathy characterized by a unique seizure type-head nodding-and associated with Onchocerca volvulus infection....
OBJECTIVE
Nodding syndrome is a poorly understood epileptic encephalopathy characterized by a unique seizure type-head nodding-and associated with Onchocerca volvulus infection. We hypothesized that altered immune activation in the cerebrospinal fluid (CSF) and plasma of children with nodding syndrome may yield insights into the pathophysiology and progression of this seizure disorder.
METHOD
We conducted a case-control study of 154 children (8 years or older) with long-standing nodding syndrome and 154 healthy age-matched community controls in 3 districts of northern Uganda affected by nodding syndrome. Control CSF samples were obtained from Ugandan children in remission from hematological malignancy during routine follow-up. Markers of immune activation and inflammation (cytokines and chemokines) and complement activation (C5a) were measured in plasma and CSF using ELISA or Multiplex Luminex assays. O volvulus infection was assessed by serology for anti-OV-16 IgG levels.
RESULTS
The mean (SD) age of the population was 15.1 (SD: 1.9) years, and the mean duration of nodding syndrome from diagnosis to enrollment was 8.3 (SD: 2.7) years. The majority with nodding syndrome had been exposed to O volvulus (147/154 (95.4%)) compared with community children (86/154 (55.8%)), with an OR of 17.04 (95% CI: 7.33, 45.58), P < .001. C5a was elevated in CSF of children with nodding syndrome compared to controls (P < .0001). The levels of other CSF markers tested were comparable between cases and controls after adjusting for multiple comparisons. Children with nodding syndrome had lower plasma levels of IL-10, APRIL, CCL5 (RANTES), CCL2, CXCL13, and MMP-9 compared with community controls (P < .05 for all; multiple comparisons). Plasma CRP was elevated in children with nodding syndrome compared to community children and correlated with disease severity.
SIGNIFICANCE
Nodding syndrome is associated with exposure to O. volvulus. Compared to controls, children with long-standing symptoms of nodding syndrome show evidence of complement activation in CSF and altered immune activation in plasma.
Topics: Adolescent; Animals; Case-Control Studies; Child; Complement Activation; Humans; Nodding Syndrome; Onchocerca volvulus; Uganda
PubMed: 34033255
DOI: 10.1002/epi4.12463 -
Clinical and Experimental Immunology Jul 1999This study investigated the effect of maternal Onchocerca volvulus infection on humoral and cellular responsiveness in newborn children and their mothers. Onchocerca...
This study investigated the effect of maternal Onchocerca volvulus infection on humoral and cellular responsiveness in newborn children and their mothers. Onchocerca volvulus-specific IgG isotypes and IgE were significantly elevated in infected mothers and their infants. One year post partum, O. volvulus-specific IgG4 was strongly reduced in children of infected mothers, while IgG1 responses weakened only slightly. Umbilical cord mononuclear blood cells (UCBC) and peripheral blood cells (PBMC) from mothers proliferated in response to phytohaemagglutinin (PHA), concanavalin A (Con A), and the bacterial antigens streptolysin-O (SL-O) or purified protein derivative (PPD). UCBC from neonates born to O. volvulus-infected mothers responded lower (P < 0.01) to Con A (at 5 micrograms/ml), PPD (at 10 and 50 micrograms/ml) and O. volvulus-derived antigens (OvAg) (at 35 micrograms/ml), and in parallel, a diminished cellular reactivity (P < 0.01) by PBMC was observed to OvAg in mothers positive for O. volvulus. Several Th1-type (IL-2, IL-12, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha)) and Th2-type (IL-4, IL-5, IL-10, IL-13) cytokines were secreted by UCBC and PBMC in response to OvAg, bacterial SL-O and PHA. OvAg did not stimulate IL-2 and none of the mitogens or antigens induced production of IL-4 in neonates. In response to OvAg, substantially elevated (P < 0.01) amounts of IFN-gamma were produced by UCBC from newborns of O. volvulus-infected mothers. UCBC secreted low levels of IL-5 and IL-13, while higher amounts of IL-10 were found (P < 0. 01) in newborns from onchocerciasis-free mothers. In conclusion, maternal O. volvulus-infection will sensitize in utero parasite-specific cellular immune responsiveness in neonates and activate OvAg-specific production of several Th1- and Th2-type cytokines.
Topics: Adolescent; Adult; Animals; Antibodies, Protozoan; Cytokines; Disease Susceptibility; Female; Fetal Blood; Fetal Diseases; Humans; Immunity, Cellular; Immunity, Maternally-Acquired; Immunoglobulin E; Immunoglobulin G; Infant, Newborn; Leukocytes, Mononuclear; Microfilariae; Middle Aged; Onchocerca volvulus; Onchocerciasis; Parasitemia; Pregnancy; Pregnancy Complications, Parasitic; Togo
PubMed: 10403926
DOI: 10.1046/j.1365-2249.1999.00906.x -
The American Journal of Tropical... Apr 2016Microscopic evaluation of skin biopsies is the monitoring and evaluation (M and E) method currently used by multiple onchocerciasis elimination programs in Africa....
Microscopic evaluation of skin biopsies is the monitoring and evaluation (M and E) method currently used by multiple onchocerciasis elimination programs in Africa. However, as repeated mass drug administration suppresses microfilarial loads, the sensitivity and programmatic utility of skin snip microscopy is expected to decrease. Using a pan-filarial real-time polymerase chain reaction with melt curve analysis (qPCR-MCA), we evaluated 1) the use of a single-step molecular assay for detecting and identifying Onchocerca volvulus microfilariae in residual skin snips and 2) the sensitivity of skin snip microscopy relative to qPCR-MCA. Skin snips were collected and examined with routine microscopy in hyperendemic regions of Uganda and Ethiopia (N= 500 each) and "residual" skin snips (tissue remaining after induced microfilarial emergence) were tested with qPCR-MCA. qPCR-MCA detected Onchocerca DNA in 223 residual snips: 139 of 147 microscopy(+) and 84 among microscopy(-) snips, suggesting overall sensitivity of microscopy was 62.3% (139/223) relative to qPCR-MCA (75.6% in Uganda and 28.6% in Ethiopia). These findings demonstrate the insufficient sensitivity of skin snip microscopy for reliable programmatic monitoring. Molecular tools such as qPCR-MCA can augment sensitivity and provide diagnostic confirmation of skin biopsies and will be useful for evaluation or validation of new onchocerciasis M and E tools.
Topics: Animals; Biopsy; Child; Ethiopia; Humans; Microscopy; Onchocerca volvulus; Onchocerciasis; Real-Time Polymerase Chain Reaction; Sensitivity and Specificity; Skin; Uganda
PubMed: 26880774
DOI: 10.4269/ajtmh.15-0695 -
PLoS Neglected Tropical Diseases Jul 2017Treatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug...
BACKGROUND
Treatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug administration is likely to exert selection pressure on parasites, and phenotypic and genetic changes in several Onchocerca volvulus populations from Cameroon and Ghana-exposed to more than a decade of regular ivermectin treatment-have raised concern that sub-optimal responses to ivermectin's anti-fecundity effect are becoming more frequent and may spread.
METHODOLOGY/PRINCIPAL FINDINGS
Pooled next generation sequencing (Pool-seq) was used to characterise genetic diversity within and between 108 adult female worms differing in ivermectin treatment history and response. Genome-wide analyses revealed genetic variation that significantly differentiated good responder (GR) and sub-optimal responder (SOR) parasites. These variants were not randomly distributed but clustered in ~31 quantitative trait loci (QTLs), with little overlap in putative QTL position and gene content between the two countries. Published candidate ivermectin SOR genes were largely absent in these regions; QTLs differentiating GR and SOR worms were enriched for genes in molecular pathways associated with neurotransmission, development, and stress responses. Finally, single worm genotyping demonstrated that geographic isolation and genetic change over time (in the presence of drug exposure) had a significantly greater role in shaping genetic diversity than the evolution of SOR.
CONCLUSIONS/SIGNIFICANCE
This study is one of the first genome-wide association analyses in a parasitic nematode, and provides insight into the genomics of ivermectin response and population structure of O. volvulus. We argue that ivermectin response is a polygenically-determined quantitative trait (QT) whereby identical or related molecular pathways but not necessarily individual genes are likely to determine the extent of ivermectin response in different parasite populations. Furthermore, we propose that genetic drift rather than genetic selection of SOR is the underlying driver of population differentiation, which has significant implications for the emergence and potential spread of SOR within and between these parasite populations.
Topics: Animals; Antiparasitic Agents; Cameroon; Drug Resistance; Female; Gene Expression Profiling; Genetic Drift; Genetic Variation; Genotype; Ghana; High-Throughput Nucleotide Sequencing; Humans; Ivermectin; Onchocerca volvulus; Onchocerciasis; Quantitative Trait Loci
PubMed: 28746337
DOI: 10.1371/journal.pntd.0005816 -
Pathogens (Basel, Switzerland) Jun 2021Onchocerciasis-associated epilepsy (OAE) is a devastating childhood disorder occurring in areas with high transmission. Despite epidemiological evidence showing the...
Onchocerciasis-associated epilepsy (OAE) is a devastating childhood disorder occurring in areas with high transmission. Despite epidemiological evidence showing the association between 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 infection, 18 with infection but without epilepsy, and 35 with neither infection nor epilepsy. 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 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.
PubMed: 34201076
DOI: 10.3390/pathogens10060720 -
Lancet (London, England) Oct 2018The morbidity and socioeconomic effects of onchocerciasis, a parasitic disease that is primarily endemic in sub-Saharan Africa, have motivated large morbidity and... (Randomized Controlled Trial)
Randomized Controlled Trial
Single dose moxidectin versus ivermectin for Onchocerca volvulus infection in Ghana, Liberia, and the Democratic Republic of the Congo: a randomised, controlled, double-blind phase 3 trial.
BACKGROUND
The morbidity and socioeconomic effects of onchocerciasis, a parasitic disease that is primarily endemic in sub-Saharan Africa, have motivated large morbidity and transmission control programmes. Annual community-directed ivermectin treatment has substantially reduced prevalence. Elimination requires intensified efforts, including more efficacious treatments. We compared parasitological efficacy and safety of moxidectin and ivermectin.
METHODS
This double-blind, parallel group, superiority trial was done in four sites in Ghana, Liberia, and the Democratic Republic of the Congo. We enrolled participants (aged ≥12 years) with at least 10 Onchocerca volvulus microfilariae per mg skin who were not co-infected with Loa loa or lymphatic filariasis microfilaraemic. Participants were randomly allocated, stratified by sex and level of infection, to receive a single oral dose of 8 mg moxidectin or 150 μg/kg ivermectin as overencapsulated oral tablets. The primary efficacy outcome was skin microfilariae density 12 months post treatment. We used a mixed-effects model to test the hypothesis that the primary efficacy outcome in the moxidectin group was 50% or less than that in the ivermectin group. The primary efficacy analysis population were all participants who received the study drug and completed 12-month follow-up (modified intention to treat). This study is registered with ClinicalTrials.gov, number NCT00790998.
FINDINGS
Between April 22, 2009, and Jan 23, 2011, we enrolled and allocated 998 participants to moxidectin and 501 participants to ivermectin. 978 received moxidectin and 494 ivermectin, of which 947 and 480 were included in primary efficacy outcome analyses. At 12 months, skin microfilarial density (microfilariae per mg of skin) was lower in the moxidectin group (adjusted geometric mean 0·6 [95% CI 0·3-1·0]) than in the ivermectin group (4·5 [3·5-5·9]; difference 3·9 [3·2-4·9], p<0·0001; treatment difference 86%). Mazzotti (ie, efficacy-related) reactions occurred in 967 (99%) of 978 moxidectin-treated participants and in 478 (97%) of 494 ivermectin-treated participants, including ocular reactions (moxidectin 113 [12%] participants and ivermectin 47 [10%] participants), laboratory reactions (788 [81%] and 415 [84%]), and clinical reactions (944 [97%] and 446 [90%]). No serious adverse events were considered to be related to treatment.
INTERPRETATION
Skin microfilarial loads (ie, parasite transmission reservoir) are lower after moxidectin treatment than after ivermectin treatment. Moxidectin would therefore be expected to reduce parasite transmission between treatment rounds more than ivermectin could, thus accelerating progress towards elimination.
FUNDING
UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases.
Topics: Adolescent; Animals; Anthelmintics; Democratic Republic of the Congo; Double-Blind Method; Endemic Diseases; Female; Ghana; Humans; Ivermectin; Liberia; Macrolides; Male; Microfilariae; Onchocerca volvulus; Onchocerciasis; Parasite Load; Skin
PubMed: 29361335
DOI: 10.1016/S0140-6736(17)32844-1