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Molecular Biomedicine Dec 2021
PubMed: 34907469
DOI: 10.1186/s43556-021-00062-z -
Journal of Medical Entomology Nov 2022Entomological indicators of onchocerciasis transmission and the effect of climatic variables on the vector population dynamics were investigated in two first-line...
Status of Onchocerca volvulus (Spirurida: Onchocercidae) Transmission and Effect of Climatic Variables on the Vector Population Dynamics After Two Decades of Ivermectin-based Preventive Chemotherapy in the Mbam Valley (Centre Region, Cameroon).
Entomological indicators of onchocerciasis transmission and the effect of climatic variables on the vector population dynamics were investigated in two first-line villages after more than two decades of mass drug administration with ivermectin. Female blackflies were collected in two villages (Bayomen and Biatsota) using human landing method for a period of 12 months. Blackflies were dissected and entomological indices were computed. Monthly temperature, precipitation, and humidity were collected and the Spearman correlation rank test was used to assess the relationship between biting rates and climatic variables. The highest biting rates (62,280 bites/human/month in Bayomen and 42,090 bites/human/month in Biatsota) were recorded during the long rainy season (November). The Onchocerca volvulus transmission was greater during the long dry season in both villages, with a peak at the beginning of the long dry season in Biatsota (100 infective larvae/human/month), and at the middle of the long dry season in Bayomen (92 infective larvae/human/month). No correlation was found between biting rates and selected climatic variables in the two villages. This study revealed that onchocerciasis transmission is ongoing in the study area despite almost 25 years of Community-Directed Treatment with Ivermectin. In accordance with WHO recommendations, vector control should be used in combination with mass drug administration to accelerate transmission interruption of onchocerciasis. To be optimal, this vector control should be implemented during the long dry season (November to March) when water volumes are low and transmission potentials are high.
Topics: Female; Humans; Animals; Onchocerca volvulus; Onchocerciasis; Ivermectin; Spirurida; Cameroon; Insect Vectors; Simuliidae; Population Dynamics
PubMed: 36111691
DOI: 10.1093/jme/tjac133 -
PLoS Neglected Tropical Diseases Jul 2019Onchocerca volvulus is the nematode pathogen responsible for human onchocerciasis also known as "River blindness", a neglected tropical disease that affects up to 18...
Onchocerca volvulus is the nematode pathogen responsible for human onchocerciasis also known as "River blindness", a neglected tropical disease that affects up to 18 million people worldwide. Helminths Excretory Secretory Products (ESPs) constitute a rich repertoire of molecules that can be exploited for host-parasite relationship, diagnosis and vaccine studies. Here, we report, using a range of molecular techniques including PCR, western blot, recombinant DNA technology, ELISA, high performance thin-layer chromatography and mass spectrometry that the 28 KDa cysteine-rich protein (Ov28CRP) is a reliable component of the O. volvulus ESPs to address the biology of this parasite. We showed that (1) Ov28CRP is a putative ganglioside GM2 Activator Protein (GM2AP) conserved in nematode; (2) OvGM2AP gene is transcriptionally activated in all investigated stages of the parasitic life cycle, including larval and adult stages; (3) The full-length OvGM2AP was detected in in-vitro O. volvulus ESPs of adult and larval stages; (4) the mass expressed and purified recombinant OvGM2AP purified from insect cell culture medium was found to be glycosylated at asparagine 173 and lacked N-terminal signal peptide sequence; (5) the recombinant OvGM2AP discriminated serum samples of infected and uninfected individuals; (6) OvGM2AP competitively inhibits MUG degradation by recombinant β-hexosaminidase A but not MUGS, and could not hydrolyze the GM2 to GM3; (7) humoral immune responses to the recombinant OvGM2AP revealed a negative correlation with ivermectin treatment. Altogether, our findings suggest for the first time that OvGM2AP is an antigenic molecule whose biochemical and immunological features are important to gain more insight into our understanding of host-parasite relationship, as well as its function in parasite development at large.
Topics: Animals; Cattle; Cloning, Molecular; DNA, Helminth; Female; G(M2) Activator Protein; Gene Expression Profiling; Helminth Proteins; Host-Parasite Interactions; Humans; Immunoglobulin G; Male; Onchocerca volvulus; Onchocerciasis, Ocular; Recombinant Proteins; Sequence Analysis, DNA; Sf9 Cells; Spodoptera
PubMed: 31329585
DOI: 10.1371/journal.pntd.0007591 -
Frontiers in Tropical Diseases Jan 2023Conventional diagnosis of filarial infections is based on morphological identification of microfilariae using light microscopy and requires considerable expertise, is...
Conventional diagnosis of filarial infections is based on morphological identification of microfilariae using light microscopy and requires considerable expertise, is time-consuming, and can be subjective. Loop-mediated isothermal amplification (LAMP) has advantages over microscopy or PCR because of its operational simplicity, rapidity and versatility of readout options. LAMP assays represent a major step forward in improved filarial diagnostic tools suitable for low resource settings and field applicability. The study goal was to retrospectively evaluate the performance and suitability of the O-150, RF4, and Mp419 LAMP assays for diagnosing , and infections, respectively, in humans and vectors under experimental and natural field conditions. Surveys were conducted in four health districts of Cameroon using skin snip and thick blood film methods to detect skin () and blood ( and ) dwelling microfilaria in humans. Engorged vectors (., ., and spp.) were evaluated by LAMP. Dissected, wild-caught vectors were also analyzed. LAMP showed a prevalence of 40.4% (), 17.8% () and 36.6% () versus 20.6% (), 17.4% () and 33.8% () with microscopy. spp. were dissected for microscopy and pooled for LAMP. The O-150 LAMP assay infection rate was 4.3% versus 4.1% by microscopy. spp. were dissected and analyzed individually in the LAMP assay. The RF4 LAMP assay infection rate was 23.5% versus 3.3% with microscopy. The RF4 LAMP assay also detected parasites in spp. fed on low microfilaremic volunteers. The Mp419 LAMP assay infection rate was 0.2% for and 0.04% for , while three other species were LAMP-negative. The sensitivity, species specificity, rapidity and ease of its use of these filarial LAMP assays, and validation of their performance in the field support use as alternatives to microscopy as diagnostic and surveillance tools in global health programs aimed to eliminate onchocerciasis.
PubMed: 36684508
DOI: 10.3389/fitd.2022.1016176 -
Acta Crystallographica. Section F,... Jun 2022Superoxide dismutases (SODs) are metalloproteins that are responsible for the dismutation of superoxide anion radicals. SODs are consequently protective against...
Superoxide dismutases (SODs) are metalloproteins that are responsible for the dismutation of superoxide anion radicals. SODs are consequently protective against oxidative damage to cellular components. Among other protective mechanisms, the filarial parasite Onchocerca volvulus has a well developed defense system to scavenge toxic free radicals using SODs during migration and sojourning of the microfilariae and adult worms in the human body. O. volvulus is responsible for the neglected disease onchocerciasis or `river blindness'. In the present study, an extracellular Cu/Zn-SOD from O. volvulus (OvEC-SOD) was cloned, purified and crystallized to obtain structural insight into an attractive drug target with the potential to combat onchocerciasis. The recombinant OvEC-SOD forms a dimer and the protein structure was solved and refined to 1.55 Å resolution by X-ray crystallography. Interestingly, a sulfate ion supports the coordination of the conserved copper ion. The overall protein shape was verified by small-angle X-ray scattering. The enzyme shows a different surface charge distribution and different termini when compared with the homologous human SOD. A distinct hydrophobic cleft to which both protomers of the dimer contribute was utilized for a docking approach with compounds that have previously been identified as SOD inhibitors to highlight the potential for individual structure-based drug development.
Topics: Animals; Crystallography, X-Ray; Drug Development; Intestinal Volvulus; Onchocerca volvulus; Onchocerciasis; Parasites; Superoxide Dismutase
PubMed: 35647680
DOI: 10.1107/S2053230X22005350 -
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 -
Brain Communications 2023Nodding syndrome is a neglected, disabling and potentially fatal epileptic disorder of unknown aetiology affecting thousands of individuals mostly confined to Eastern...
Nodding syndrome is a neglected, disabling and potentially fatal epileptic disorder of unknown aetiology affecting thousands of individuals mostly confined to Eastern sub-Saharan Africa. Previous studies have identified multiple associations-including , antileiomodin-1 antibodies, vitamin B deficiency and measles virus infection-yet, none is proven causal. We conducted a case-control study of children with early-stage nodding syndrome (symptom onset <1 year). Cases and controls were identified through a household survey in the Greater Mundri area in South Sudan. A wide range of parasitic, bacterial, viral, immune-mediated, metabolic and nutritional risk factors was investigated using conventional and state-of-the-art untargeted assays. Associations were examined by multiple logistic regression analysis, and a hypothetical causal model was constructed using structural equation modelling. Of 607 children with nodding syndrome, 72 with early-stage disease were included as cases and matched to 65 household- and 44 community controls. infection (odds ratio 7.04, 95% confidence interval 2.28-21.7), infection (odds ratio 2.33, 95% confidence interval 1.02-5.3), higher antimalarial seroreactivity (odds ratio 1.75, 95% confidence interval 1.20-2.57), higher vitamin E concentration (odds ratio 1.53 per standard deviation increase, 95% confidence interval 1.07-2.19) and lower vitamin B concentration (odds ratio 0.56 per standard deviation increase, 95% confidence interval 0.36-0.87) were associated with higher odds of nodding syndrome. In a structural equation model, we hypothesized that infection, higher vitamin E concentration and fewer viral exposures increased the risk of nodding syndrome while lower vitamin B concentration, and malaria infections resulted from having nodding syndrome. We found no evidence that antileiomodin-1 antibodies, vitamin B and other factors were associated with nodding syndrome. Our results argue against several previous causal hypotheses including . Instead, nodding syndrome may be caused by a complex interplay between multiple pathogens and nutrient levels. Further studies need to confirm these associations and determine the direction of effect.
PubMed: 37731906
DOI: 10.1093/braincomms/fcad223 -
PLoS Neglected Tropical Diseases Oct 2021Nodding syndrome (NS) is a catastrophic and enigmatic childhood epilepsy, accompanied by multiple neurological impairments and neuroinflammation. Of all the infectious,...
Nodding syndrome (NS) is a catastrophic and enigmatic childhood epilepsy, accompanied by multiple neurological impairments and neuroinflammation. Of all the infectious, environmental and psychological factors associated with NS, the major culprit is Onchocerca Volvulus (Ov)-a parasitic worm transmitted to human by blackflies. NS seems to be an 'Autoimmune Epilepsy' in light of the recent findings of deleterious autoimmune antibodies to Glutamate receptors and to Leiomodin-I in NS patients. Moreover, we recently found immunogenetic fingerprints in HLA peptide-binding grooves associate with protection or susceptibility to NS. Macrophage migration inhibitory factor (MIF) is an immune-regulatory cytokine playing a central role in modulating innate and adaptive immunity. MIF is also involved in various pathologies: infectious, autoimmune and neurodegenerative diseases, epilepsy and others. Herein, two functional polymorphisms in the MIF gene, a -794 CATT5-8 microsatellite repeat and a -173 G/C single-nucleotide polymorphism, were assessed in 49 NS patients and 51 healthy controls from South Sudan. We also measured MIF plasma levels in established NS patients and healthy controls. We discovered that the frequency of the high-expression MIF -173C containing genotype was significantly lower in NS patients compared to healthy controls. Interestingly however, MIF plasma levels were significantly elevated in NS patients than in healthy controls. We further demonstrated that the HLA protective and susceptibility associations are dominant over the MIF association with NS. Our findings suggest that MIF might have a dual role in NS. Genetically controlled high-expression MIF genotype is associated with disease protection. However, elevated MIF in the plasma may contribute to the detrimental autoimmunity, neuroinflammation and epilepsy.
Topics: Adolescent; Adult; Animals; Child; Child, Preschool; Female; Genotype; Humans; Macrophage Migration-Inhibitory Factors; Male; Microsatellite Repeats; Nodding Syndrome; Onchocerca volvulus; Polymorphism, Single Nucleotide; Young Adult
PubMed: 34662363
DOI: 10.1371/journal.pntd.0009821 -
GMS Infectious Diseases 2022Filarial diseases like lymphatic filariasis and onchocerciasis belong to the Neglected Tropical Diseases and remain a public health problem in endemic countries.... (Review)
Review
Filarial diseases like lymphatic filariasis and onchocerciasis belong to the Neglected Tropical Diseases and remain a public health problem in endemic countries. Lymphatic filariasis and onchocerciasis can lead to stigmatizing pathologies and present a socio-economic burden for affected people and their endemic countries. Current treatment recommendations by the WHO include mass drug administration with ivermectin for the treatment of onchocerciasis and a combination of ivermectin, albendazole and diethylcarbamazine (DEC) for the treatment of lymphatic filariasis in areas that are not co-endemic for onchocerciasis or loiasis. Limitations of these treatment strategies are due to potential severe adverse events in onchocerciasis and loiasis patients following DEC or ivermectin treatment, respectively, the lack of a macrofilaricidal efficacy of those drugs and the risk of drug resistance development. Thus, to achieve the elimination of transmission of onchocerciasis and the elimination of lymphatic filariasis as a public health problem by 2030, the WHO defined in its roadmap that new alternative treatment strategies with macrofilaricidal compounds are required. Within a collaboration of the non-profit organizations Drugs for Neglected Diseases initiative (DND), the Bill & Melinda Gates Foundation, and partners from academia and industry, several new promising macrofilaricidal drug candidates were identified, which will be discussed in this review.
PubMed: 35463816
DOI: 10.3205/id000079 -
PLoS Neglected Tropical Diseases Jun 2023Nodding syndrome (NS) has been consistently associated with onchocerciasis. Nevertheless, a positive association between NS and a Mansonella perstans infection was found...
BACKGROUND
Nodding syndrome (NS) has been consistently associated with onchocerciasis. Nevertheless, a positive association between NS and a Mansonella perstans infection was found in South Sudan. We aimed to determine whether the latter parasite could be a risk factor for NS in Mahenge.
METHODS
Cases of epilepsy were identified in villages affected by NS in Mahenge, Tanzania, and matched with controls without epilepsy of the same sex, age and village. We examined blood films of cases and controls to identify M. perstans infections. The participants were also asked for sociodemographic and epilepsy information, examined for palpable onchocercal nodules and onchocerciasis-related skin lesions and tested for anti-Onchocerca volvulus antibodies (Ov16 IgG4) by ELISA. Clinical characteristics of cases and controls, O. volvulus exposure status and relevant sociodemographic variables were assessed by a conditional logistic regression model for NS and epilepsy status matched for age, sex and village.
RESULTS
A total of 113 epilepsy cases and 132 controls were enrolled, of which, respectively, 56 (49.6%) and 64 (48.5%) were men. The median age in cases and controls was 28.0 (IQR: 22.0-35.0) and 27.0 (IQR: 21.0-33.3) years. Of the persons with epilepsy, 43 (38.1%) met the probable NS criteria and 106 (93.8%) had onchocerciasis-associated epilepsy (OAE). M. perstans infection was absent in all participants, while Ov16 seroprevalence was positively associated with probable NS (odds ratio (OR): 5.05, 95%CI: 1.79-14.27) and overall epilepsy (OR: 2.03, 95%CI: 1-07-3.86). Moreover, onchocerciasis-related skin manifestations were only found in the cases (n = 7, p = 0.0040), including persons with probable NS (n = 4, p = 0.0033). Residing longer in the village and having a family history of seizures were positively correlated with Ov16 status and made persons at higher odds for epilepsy, including probable NS.
CONCLUSION
In contrast to O. volvulus, M. perstans is most likely not endemic to Mahenge and, therefore, cannot be a co-factor for NS in the area. Hence, this filaria is unlikely to be the primary and sole causal factor in the development of NS. The main risk factor for NS remains onchocerciasis.
Topics: Male; Animals; Humans; Young Adult; Adult; Female; Onchocerca volvulus; Onchocerciasis; Mansonella; Tanzania; Case-Control Studies; Nodding Syndrome; Intestinal Volvulus; Seroepidemiologic Studies; Epilepsy; Risk Factors
PubMed: 37339148
DOI: 10.1371/journal.pntd.0011434