Publications by authors named "M W Lightowlers"

198 Publications

Immunodiagnostic usefulness of monoclonal antibodies specific to conformational epitopes of Taenia solium oncosphere protein TSOL18.

J Immunol Methods 2021 Oct 2;497:113121. Epub 2021 Aug 2.

Institute of tropical Medicine, Department of Biomedical Sciences, Nationale Straat 155, B-2000 Antwerp, Belgium.

Taenia solium oncosphere protein TSOL18 is the host-protective antigen against porcine cysticercosis. Little attention has been given to use it as target molecule in immunodiagnostic tests. The objective of this paper is to describe the immunodiagnostic potential of monoclonal antibodies (MoAbs) raised against conformational epitopes of TSOL18. Three murine IgG1 MoAbs (25D12C1, 21C2D2, 10H1F2) against three different conformational epitopes of TSOL18 were produced and evaluated with an inhibition enzyme-linked immunosorbent assay (i-ELISA) for the detection of anti-TSOL18 and anti-oncosphere antibodies. Serum samples from pigs immunized with TSOL18 inhibited the binding of the three MoAbs to TSOL18 antigen in i-ELISA. The highest inhibition of anti-TSOL18 antibodies in immunized pigs was observed with MoAb 25D12C1. Ten field sera (12.19%) from 82 non-vaccinated and non-infected pigs showed anti-oncosphere antibodies inhibiting the binding of MoAb 25D12C1. Anti-oncosphere antibodies in pigs experimentally infected with T. solium eggs inhibited the binding of MoAb 25D12C1 from 2 to 8 week-post infection. It is concluded that MoAb 25D12C1 has excellent immunodiagnostic potentials to detect anti-oncosphere antibodies in the intermediate hosts at early exposure to T. solium eggs. Further investigations on potential use of MoAb 25D12C1 in a capture antigen ELISA for the detection of post-oncospheral antigens in infected pigs cannot be overemphasized.
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http://dx.doi.org/10.1016/j.jim.2021.113121DOI Listing
October 2021

Control trial of porcine cysticercosis in Uganda using a combination of the TSOL18 vaccination and oxfendazole.

Infect Dis Poverty 2021 Mar 20;10(1):34. Epub 2021 Mar 20.

Faculty of Veterinary and Agricultural Sciences, University of Melbourne, 250 Princes Highway, Werribee, VIC, 3030, Australia.

Background: Neurocysticercosis caused by Taenia solium when the parasite lodges in the central nervous system, is an important cause of human seizures and mortality in sub-Saharan Africa. The parasite is prevalent in many regions of Uganda. Pigs are intermediate hosts for T. solium, and we evaluated a T. solium control program in pigs, involving vaccination of pigs with the TSOL18 vaccine and treatment with oxfendazole.

Methods: The study was conducted in two districts of Eastern Uganda involving the rural village communities of Bukedea (intervention area) and Kumi (control area) during 2016-2017. Seven hundred and thirty-four households were enrolled in the study. Pigs in the intervention area received intramuscular immunizations with TSOL18 (Cysvax™) and an oral medication with 30 mg/kg oxfendazole (Paranthic™) at approximately 3-monthly intervals for 18 months. Porcine cysticercosis was evaluated by post-mortem examination. At the beginning of the study, 111 pigs were examined. In an interim evaluation in the intervention area, 55 pigs were evaluated 12 months after starting the project. At the end of the study approximately 3 months after the final intervention, 55 pigs from the intervention area and 56 pigs from the control area were evaluated.

Results: The prevalence of porcine cysticercosis for the two sites was 16.2% at the beginning of the study (17.2% in the intervention area and 15.1% in the control area) with no statistically significant difference (P = 0.759) between the two study sites. Among the 110 animals assessed from the intervention site (55 at the interim evaluation and 55 at the final evaluation), no pig with viable T. solium cysts was found. There was a statistically significant difference between the prevalence at baseline (17.2%) and at the end of the study (0%) in the intervention area (P = 0.001) and a statistically significant difference between the intervention (0%) and control areas (5.4%) (P = 0.041) at the end of the study.

Conclusions: Three-monthly concurrent vaccination of pigs with the TSOL18 vaccine and medication with oxfendazole eliminated T. solium transmission by the animals involved in the study. Application of vaccination with medication in pigs has the potential to reduce transmission of T. solium in Uganda and other endemic countries.
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http://dx.doi.org/10.1186/s40249-021-00823-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981864PMC
March 2021

Combined use of two separate but protective vaccine antigens provides protection against Taenia ovis infection in lambs in the presence of protective maternal antibody.

Vaccine 2021 04 16;39(15):2035-2040. Epub 2021 Mar 16.

University of Melbourne, Faculty of Veterinary and Agricultural Sciences, 250 Princes Highway, Werribee, Victoria 3030, Australia.

Three recombinant Taenia ovis antigens (To45, To16, To18) each induce protective immunity in lambs or ewes against infection with T. ovis metacestodes. The degree and duration of immunity were assessed in lambs born from vaccinated ewes. Treatment group sizes varied, typically not fewer than 5 animals per group. Ewes were immunised with one T. ovis recombinant protein prior to lambing and the degree and duration of passive immunity in their lambs was assessed by challenge infection up to 18 weeks. Lambs were fully protected up to 6 weeks of age but immunity waned from 6 to 12 weeks and there was no protection when lambs were challenged at 15 weeks. Immunisation of lambs with the homologous recombinant antigen was not effective when vaccinations were given when maternal antibody was high. Lambs were effectively immunised in the presence of passively protective antibody when vaccinated with an antigen that was different to that given to ewes. Vaccination of lambs with a combination of two proteins, To16 and To18, was more effective than giving these single antigens and gave a significant reduction of cyst numbers when lambs were challenged 12 months after immunisation. These results indicate that the use of combinations of T. ovis recombinant antigens could enable complete protection of lambs against infection, if a delivery system becomes available that will maintain antibody at protective levels for 12 months. Alternatively, a third injection given at 6 months may promote the anamnestic response to give long lasting protection.
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http://dx.doi.org/10.1016/j.vaccine.2021.03.029DOI Listing
April 2021

Control of cystic echinococcosis in the Middle Atlas, Morocco: Field evaluation of the EG95 vaccine in sheep and cesticide treatment in dogs.

PLoS Negl Trop Dis 2021 03 8;15(3):e0009253. Epub 2021 Mar 8.

Integrated Veterinary Research Unit, Department of Veterinary Medicine, Namur Research Institute for Life Sciences (NARILIS), University of Namur, Belgium.

Background: Cystic echinococcosis (CE) is an important cause of human morbidity and mortality worldwide, particularly in Morocco and other North African countries.

Methodology/principal Findings: We investigated the potential of three strategies to reduce Echinococcus granulosus transmission: (1) 4-monthly treatment of dogs with praziquantel, (2) vaccination of sheep with the EG95 vaccine and (3) a combination of both measures. These measures were implemented during four consecutive years in different areas of the Middle Atlas Mountains in Morocco. The outcome of the interventions was assessed through hydatid cyst (viable and non-viable) counts in liver and lungs using necropsy or in vivo ultrasound examination of the liver. A total of 402 lambs were recruited for annual vaccination with the EG95 anti-E. granulosus vaccine and 395 similar lambs were selected as non-vaccinated controls. At approximately four years of age the relative risk (estimated as odds ratio) for vaccinated sheep to have viable hydatid cysts compared with non-vaccinated controls was 3% (9.37% of the vaccinated sheep were found infected while 72.82% of the controls were infected; p = 0.002). The number of viable cysts in vaccinated animals was reduced by approximately 97% (mean counts were 0.28 and 9.18 respectively; p<0.001). An average of 595 owned dogs received 4-monthly treatment during the 44 months trial, corresponding to 91% of the owned dog population. Approximately, 5% of them were examined for E. granulosus adult worms by arecoline purge or eggs in feces (confirmed by PCR). The proportion of infected dogs significantly decreased after treatment (12% versus 35%; p<0.001). Post-treatment incidence of re-infestation corresponded to a monthly risk of 4% (95% CI: 3-6%). Treatment of owned dogs on a 4-monthly basis did not reduce the level of transmission of E. granulosus to sheep, nor did it enhance the level of control generated by vaccination of sheep with EG95, possibly because of unowned dogs and wild canids were not treated.

Conclusions/significance: These data suggest that vaccination of sheep with EG95 has the potential to reduce the level of CE in Morocco and in other parts of the world with similar transmission dynamics. Under the epidemiological circumstances existing in the trial area, 4-monthly treatment of owned dogs with praziquantel was insufficient to have a major impact of E. granulosus transmission to sheep.
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http://dx.doi.org/10.1371/journal.pntd.0009253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971873PMC
March 2021

Performance of Ag-ELISA in the diagnosis of Taenia solium cysticercosis in naturally infected pigs in Tanzania.

Parasit Vectors 2020 Oct 27;13(1):534. Epub 2020 Oct 27.

Department of Veterinary Medicine and Public Health, College of Veterinary Medicine and Biomedical Sciences, Sokoine University of Agriculture, Morogoro, Tanzania.

Background: Taenia solium is a zoonotic parasite responsible for neurocysticercosis-a major cause of late-onset acquired epilepsy in humans. Lack of affordable, specific and sensitive diagnostic tools hampers control of the parasite. This study assessed the performance of an antigen detection enzyme-linked immunosorbent assay (Ag-ELISA) in the diagnosis of viable T. solium cysticercosis in naturally infected slaughter-age pigs in an endemic area in Tanzania.

Methods: A total of 350 pigs were bled before they were slaughtered and their carcases examined. Serum was analyzed for circulating antigens by using a monoclonal antibody-based B158/B60 Ag-ELISA. Each carcase was examined for the presence of Taenia hydatigena cysticerci and half carcase musculature together with the whole brain, head muscles, tongue, heart and diaphragm were sliced with fine cuts (< 0.5 cm) to reveal and enumerate T. solium cysticerci. Half carcase dissection can detect at least 84% of infected pigs. Prevalence and their 95% confidence intervals (CI) were calculated in Stata 12. Sensitivity, specificity, predictive values and likelihood ratios were determined.

Results: Twenty-nine pigs (8.3%, 95% CI: 5.6-11.7%) had viable T. solium cysticerci while 11 pigs had T. hydatigena cysticerci (3.1%, 95% CI: 1.6-5.5%). No co-infection was observed. Sixty-eight pigs (19.4%, 95% CI: 15.4-20%) tested positive on Ag-ELISA; of these, 24 had T. solium cysticerci and 7 had T. hydatigena cysticerci. Sensitivity and specificity were determined to be 82.7% and 86.3%, respectively. Positive and negative predictive values were 35.2% and 98.2%, respectively. Likelihood ratios for positive and negative Ag-ELISA test results were 6.0 and 0.2, respectively. There was a significant positive correlation between the titre of circulating antigens and intensity of T. solium cysticerci (r = 0.63, P < 0.001).

Conclusions: The Ag-ELISA test characteristics reported in this study indicate that the test is more reliable in ruling out T. solium cysticercosis in pigs, than in confirming it. Hence, a negative result will almost certainly indicate that a pig has no infection, but a positive result should always be interpreted with caution. Estimates of T. solium prevalence based on Ag-ELISA results should, therefore, be adjusted for test performance characteristics and occurrence of T. hydatigena.
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http://dx.doi.org/10.1186/s13071-020-04416-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590492PMC
October 2020
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