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Onchocerciasis

Onchocerciasis is a multifaceted parasitic disease that affects public health in endemic areas. At Protheragen, we appreciate that every project has its particularities and thus requires specific approaches. We are able to develop and provide flexible and innovative solutions regarding clients' specific needs in onchocerciasis diagnostics and therapeutics development.

Introduction to Onchocerciasis

Onchocerciasis or river blindness is classified as a neglected tropical disease. Its causative agent is Onchocerca Volvulus, a parasitic nematode. The disease is transmitted to humans through the bite of an infected blackfly of the genus Simulium, which lays its eggs in rivers and streams with fast-flowing waters. The resulting infection causes intolerable itching, skin lesions, eye problems, and even total blindness. Onchocerciasis is endemic in 37 countries, and most attacks are in sub-Saharan Africa, with some other foci in Latin America and Yemen. Millions are affected by this disease, leading to severe morbidity and disability.

Phases in the elimination of human onchocerciasis.Fig.1 Elimination of onchocerciasis in humans. (Lakwo T., et al., 2020)

Diagnostics Development for Onchocerciasis

  • Serological Tests
    The World Health Organization (WHO) suggests Implementing the Ov16 enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies to the Ov16 antigen. This test can be employed to show the interruption of transmission in elimination programs. There are rapid diagnostic tests (RDTs) that incorporate the Ov16 antigen which serves as a quicker and more user-friendly substitute compared to ELISA.
  • Molecular Methods
    Methods based on targeted PCR for specific DNA sequences such as the O-150 repeat have been designed to find Onchocerca volvulus in skin snips. Assays for Loop-Mediated Isothermal Amplification (LAMP) offer a fast colorimetric field detection system that is as sensitive and specific as PCR.
  • Entomological Surveillance
    The extraction of DNA from pools of blackflies to check for the presence of Onchocerca Volvulus through the polymerase chain reaction (PCR) is a form of entomological surveillance. This method is inexpensive and permits for an extensive collection of flies which can be used to verify the cessation of transmission. The trap Esperanza Window Trap (EWT) is a new particular type of trap used for blackflies that captures them using visual and smell attractants.

Table 1. Candidate antigens are considered for diagnosis of onchocerciasis. (Unnasch T. R., et al., 2018)

MW (kDa) Antigen(s) Associated Protein Specificity (%) Sensitivity (%) Test used
15 OV103 MF surface-associated protein 70 57 ELISA
16 OV16 Phosphatidyl ethanolamine binding protein 96 96 ELISA
17 OV10 Cysteine proteinase inhibitor 100 61 ELISA
19–20 OvMPB/10 Not determined 100 78 ELISA
20 OV11 Retinol binding protein 96 54 ELISA
OvMPB/11 99 65 ELISA
Ov-Far-1 100 100 IgG4 LIPS assay
20–23 OV 31 Not determined 92 68 ELISA
OV 31 100 Microplaque spot analysis
28 MSP-2 Major sperm protein 85 100 Dot blot assay
33 OC 3.6 Aspartyl protease inhibitor n/a 93 ELISA
OV33-GST 96 93 ELISA
C27 n/a 82 Recombinant OV33/ELISA
C71 n/a 85 Recombinant OV33/ELISA
Ov-API-1 100 100 IgG4 LIPS assay
OV 33/5M 100 n/a ELISA

Therapeutics Development for Onchocerciasis

Current Therapeutics

Ivermectin is used to manage onchocerciasis by decreasing the microfilariae present in the skin and the eyes. It is provided through massive drug intake (MDA) campaigns and has significantly controlled, and even eliminated, the disease in some parts of the world. In addition, doxycycline, which is active against the endosymbiotic Wolbachia bacteria, can also sterilize or even kill adult worms which greatly reduces the transmission potential.

New Therapeutic Approaches

The FDA's recent approval of Moxidectin is likely to be useful because of its strong microfilaricidal effect which may surpass that of Ivermectin. On-going studies are being conducted to find more effective agents against wolbachia, for example, flubentylosin and AWZ1066S, which may make therapeutics more effective and shorten its duration. These new approaches strengthen the possibility of achieving success in comabating onchocerciasis.

Our Services

Protheragen pursues innovation in the onchocerciasis diagnosis and therapeutic development services. Our work covers the entire spectrum of activities involving new molecular diagnostic and innovative therapeutic development and implementation.

Diagnostics Development

  • Karyotype Analysis Service
  • Omics Analysis Service
  • Biomarker Development Service
  • Artificial Intelligence Service

Therapeutic Development

  • Small Molecule Drug
  • Cell Therapy
  • Gene Therapy
  • Therapeutic Antibody
  • Therapeutic Peptide
  • Therapeutic Protein
  • Customized Therapy Development

Disease Models

  • Brugia pahangi Infection Models
  • Acanthochieloma viteae Infection Models
  • Onchocerca gutturosa Infection Models
  • Onchocerca linealis Infection Models

Preclinical Research

  • Pharmacodynamics Study Services
  • Pharmacokinetics Study Services
  • Drug Safety Evaluation Services
  • Customized Research Services

The preclinical research services offered by Protheragen encompass various methodologies like in vitro and in vivo tests, pharmacokinetics as well as pharmacodynamics studies, and safety evaluation. We collaborate closely with our clients to formulate and realize strategies that tackle the specific problems posed by onchocerciasis. If you are interested in our services, please feel free to contact us.

References

  • Lakwo, Thomson, et al. "Onchocerciasis elimination: progress and challenges." Research and Reports in Tropical Medicine (2020): 81-95.
  • Unnasch, Thomas R., et al. "Diagnostics for onchocerciasis in the era of elimination." International health 10.suppl_1 (2018): i20-i26.