An Immunogenic
            <i>Onchocerca volvulus</i>
            Antigen: a Specific and Early Marker of Infection

Lobos, Edgar; Weiss, N.; Karam, M; Taylor, Hugh R.; Ottesen, Eric A.; Nutman, Thomas B.

doi:10.1126/science.2011741

Cited by 138 publications

(109 citation statements)

References 11 publications

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“…Low-molecular weight filarial antigens, either isolated from crude worm extracts or produced as recombinant polypeptides, have been proposed for reliable, early serodiagnosis (Weiss & Karam 1989;Lobos et al 1991;Ramachandran 1993), as well as for the classification of different clinical forms of disease (Cabrera et al 1988;Gallin et al 1989). In support, we found a higher specificity of VLMW-OvAg compared to antigens of higher molecular masses.…”

Section: Discussionsupporting

confidence: 79%

Antigenicity and specificity of very low molecular weight Onchocerca volvulus polypeptides in the range 2.2–12.5 kD

Hoffmann

Blanke

Maier

et al. 1997

Tropical Med Int Health

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SummaryOnchocerca volvulus polypeptides in the molecular mass range of 2.2 to 12.5 kD were separated by Tricine-SDS-PAGE and the serological recognition of these very low molecular weight antigens (VLMW-OvAg) was then investigated by immuno-blotting. Sera from 21 onchocerciasis patients as well as from 53 individuals with other filariases were used to determine the sensitivity and specificity of detection of individual VLMW-OvAg. In onchocerciasis patients, up to 16 VLMWOvAg were recognized predominantly by IgG1 and IgG4, while only few antigens were recognized by IgG2 and IgG3. The antigen recognition pattern varied individually, but 4 VLMW-OvAg of 8.6, 6.2, 5.4, and 5.1 kD, respectively, were bound by IgG4 from more than 90% of the onchocerciasis patients. Six VLMW-OvAg of 7.3, 5.8, 5.4, 4.0, 3.8, and 3.6 kD were recognized exclusively by IgG1 from onchocerciasis patients. In amicrofilaraemic filariasis patients with lymphatic pathology, a strong reactivity of IgG3 to an OvAg of 2.2 kD was observed, indicating a possible contribution of this antigen to the pathogenesis. In the molecular mass range below 13 kD, no specific carbohydrate residues or phosphorylcholine-containing (PC) determinants could be identified by lectin-blotting or PC-specific immunoblotting, respectively. Two-dimensional separation and immunoblotting distinctly resolved more than 40 antigenic polypeptides, the majority focusing at acidic isoelectric points. In O. volvulus-infected chimpanzees the IgG1-and IgG4-reactivity against OvAg below 13 kD appeared concurrently with onset of patent infection. These data suggest that some of these VLMW-OvAg might be associated with the production and release of microfilariae from gravid female worms as well as be involved in immune-mediated pathogenesis during filarial infections.

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Section: Discussionsupporting

confidence: 79%

Antigenicity and specificity of very low molecular weight Onchocerca volvulus polypeptides in the range 2.2–12.5 kD

Hoffmann

Blanke

Maier

et al. 1997

Tropical Med Int Health

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“…The 100% sensitivity of our test recorded in four of the five geographic regions tested is an improvement of previous results, 9,[11][12][13]19,26,27 and shows that the combination of both immunodiagnostic antigens into one hybrid protein had a cumulative effect. Currently, we do not have an explanation for the lack of seroreactivity of two Ecuadorian onchocerciasis sera with OvH2 or OvH3.…”

Section: Discussionsupporting

confidence: 67%

“…Therefore, antibody detection assays have been developed using recombinant O. volbulus antigens. [8][9][10][11][12][13][14] Some of these antigens were tested in a multicenter trial organized by the Tropical Diseases Research Program of the WHO that identified highly specific proteins, 15 and high sensitivity of these tests was achieved by combining three proteins in a diagnostic cocktail. 13,16,17 However, these antigens were difficult to produce and the fact that they were expressed as fusions with a carrier protein made it necessary to run parallel tests to rule out antibody reactions with the carrier.…”

Section: Introductionmentioning

confidence: 99%

Sensitive and specific serodiagnosis of onchocerciasis with recombinant hybrid proteins.

Nde¹,

Pogonka²,

Bradley³

et al. 2002

The American Journal of Tropical Medicine and Hygiene

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Abstract. Onchocerciasis remains a major health hazard in many tropical countries. However, the existing tools for diagnosis of the disease have limitations, particularly regarding the detection of low level or early infections. To design an optimized reagent, we exploited the high antibody reactivity of patient sera against the Onchocerca volvulus proteins Ov20 and Ov33, which have been described as highly sensitive and specific immunodiagnostic reagents for producing hybrid proteins. The construct OvH2 was composed of Ov20 fused to Ov33, while OvH3 consisted of the C-terminus of Ov20 linked to Ov33. When these constructs were tested with sera from patients with onchocerciasis and control sera, OvH2 showed a sensitivity of 98.5% and a specificity of 97.7% and OvH3 showed a sensitivity of 98.5% and a specificity of 95.35%. All non-responders were from Ecuador. These results surpass those of existing single recombinant antigens, suggesting that our hybrid proteins combined the sensitivity of the two parent proteins. Tests based on OvH2 should prove suitable for monitoring onchocerciasis control programs and individual diagnosis.

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“…A serosurvey was conducted from a representative sample of young children to determine the CEZ prevalence of IgG4 antibodies to the O. volvulus recombinant antigen Ov-16. 22 WHO guidelines for elimination require an infection rate of < 0.1% in children under 5 years of age, and to satisfy this requirement, a sample of at least 3,000 was needed to determine a one-sided 95% confidence interval (CI) that excluded 0.1%. Assuming a 20% refusal rate to participate, we determined a target sample of 3,800.…”

Section: Methodsmentioning

confidence: 99%

One Hundred Years After Its Discovery in Guatemala by Rodolfo Robles, Onchocerca volvulus Transmission Has Been Eliminated from the Central Endemic Zone

Richards¹,

Rizzo²,

Espinoza³

et al. 2015

The American Journal of Tropical Medicine and Hygiene

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Abstract. We report the elimination of Onchocerca volvulus transmission from the Central Endemic Zone (CEZ) of onchocerciasis in Guatemala, the largest focus of this disease in the Americas and the first to be discovered in this hemisphere by Rodolfo Robles Valverde in 1915. Mass drug administration (MDA) with ivermectin was launched in 1988, with semiannual MDA coverage reaching at least 85% of the eligible population in > 95% of treatment rounds during the 12-year period, 2000-2011. Serial parasitological testing to monitor MDA impact in sentinel villages showed a decrease in microfilaria skin prevalence from 70% to 0%, and polymerase chain reaction (PCR)-based entomological assessments of the principal vector Simulium ochraceum s.l. showed transmission interruption by 2007. These assessments, together with a 2010 serological survey in children 9-69 months of age that showed Ov16 IgG4 antibody prevalence to be < 0.1%, meeting World Health Organization (WHO) guidelines for stopping MDA, and treatment was halted after 2011. After 3 years an entomological assessment showed no evidence of vector infection or recrudescence of transmission. In 2015, 100 years after the discovery of its presence, the Ministry of Health of Guatemala declared onchocerciasis transmission as having been eliminated from the CEZ. INTRODUCTION Human onchocerciasis (river blindness) is caused byOnchocerca volvulus, a tissue-dwelling filarial nematode transmitted by certain species of the genus Simulium.1 Adult male and female worms form fibrous, often palpable, subcutaneous onchocercomas ("nodules"), in which fertilized female worms produce microfilariae (mf). The mf leave the nodule and reside in the dermis. They may also enter the eyes. Human disease results largely from death of the mf, which results in inflammation, itching, visual impairment, and blindness. The Simulium ("black fly") vectors breed in rapidly flowing rivers and streams and become infected when they ingest mf during a blood meal; in competent black fly species, mf develop into third stage larvae that can infect humans when the vector takes a subsequent blood meal. There are no important animal reservoirs of O. volvulus to maintain the transmission cycle independent of the human population itself. Human onchocerciasis is thought to have originated in Africa when Onchocerca species in ungulates adapted to man; the parasite is believed to have been brought to the Americas through the Atlantic slave trade.3 Transmission was only focally established in the Americas, in contrast to the extensive transmission zones that exist in Africa. In the Americas, due to a limited distribution of competent vectors, transmission zones ("foci") are small and sharply delimited geographically, and are generally maintained by high vector biting rates. Before control measures were implemented, there were 13 foci in six countries in Latin America (Brazil, Colombia, Ecuador, Guatemala, Mexico, and Venezuela), with an overall human population at risk in 2013 of just over 500,000 persons. 4Guatemala...

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An Immunogenic Onchocerca volvulus Antigen: a Specific and Early Marker of Infection

Cited by 138 publications

References 11 publications

Antigenicity and specificity of very low molecular weight Onchocerca volvulus polypeptides in the range 2.2–12.5 kD

Antigenicity and specificity of very low molecular weight Onchocerca volvulus polypeptides in the range 2.2–12.5 kD

Sensitive and specific serodiagnosis of onchocerciasis with recombinant hybrid proteins.

One Hundred Years After Its Discovery in Guatemala by Rodolfo Robles, Onchocerca volvulus Transmission Has Been Eliminated from the Central Endemic Zone

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