Molecular epidemiology network for promotion and support of delivery of life vaccines against Theileria parva and Theileria annulata infection in Eastern and Northern Africa
Veterinary Medical Science
Final Report Abstract
The project of the molecular epidemiology network concerned the live vaccination against Theileriosis. Notwithstanding the major economic importance of Theileriosis, we recognized from the outset that there was insufficient knowledge of the epidemiological considerations relevant to the development and deployment of live vaccines. Given the lack of investigative tools for studying the epidemiology of Theileriosis in the partner laboratories, our training program was initially intended to improve the capacity of the partners to undertake accurate (both sensitive and specific) diagnosis of theileriosis in cattle. The technologies for improved disease diagnosis that we disseminated included: (i) Indirect ELISAs, (ii) reverse line blot (RLB) assays, (iii) Nested PCR-based assays, and (iv) loop-mediated isothermal amplification assays (LAMP). These epidemiological investigations resulted in the detection of parasites in areas that were hitherto thought to be free of Theileria, such as Darfur, North Kordofan State and southern parts of Blue Nile of the Sudan. In addition, significantly higher prevalence of T. annulata infections were recorded in areas such as EL-Wady EL-Geded province in Egypt. Subsequently, selected local strains of the T. annulata were attenuated by lengthy in vitro propagation of infected cell lines to produce deployable live vaccines in Egypt, Sudan and Tunisia. Here an important component of the research was aimed at simplifying the production regime for culture-attenuated vaccines with the goal of achieving attenuation at significantly lower resource costs, and more acceptably to animal welfare interests. To this end, we have demonstrated that serum free media can be used for propagation of different strains of T. annulata to achieve attenuation just as satisfactorily as in the case of serum containing media, but with a significant reduction in generation doubling times. We have also identified novel biomarkers of attenuation that enables vaccine characterization and standardization. Our research on the culture-attenuated T. annulata live vaccines was conducted with a view to their practical use. In particular, we addressed the question of how vaccine efficacy based on laboratory experimentation relates to levels of effectiveness required for impact in the field. Our work makes it clear that that the vaccines are protective against T. annulata under conditions of natural transmission. In specific places in Sudan and Tunisia where the culture attenuated vaccines were not deemed efficacious enough on their own, we demonstrated that the partial protection could be enhanced by a ‘prime-boost’ regime using experimental subunit vaccines. Besides showing that T. parva is an emerging pathogen based on evidence for geographical spread from endemic areas in East Africa, North into Southern Sudan and West into Cameroon, we have also provided objective information with which to address the concerns of policy makers relating to live ITM vaccination. In a longitudinal study, we demonstrated that although ITM generates a long-term carrier state, PCR detectable for up to 14 years post-vaccination, there were no major impacts on parasite population genetic structure after deployment. We also showed that the antigen gene sequences present within the ITM cocktail are relatively conserved among cattle transmissible T. parva populations in new target areas for deployment. The contribution of buffalo-to-cattle transmission of T. parva is also now better understood as a result of our work. In sum, it is clear that live vaccines can have an appreciable impact on Theileriosis control and our research has addressed the major constraints to their widespread use.
Publications
- (2020). A review of recent research on Theileria parva: implications for the infection and treatment vaccination method for control of East Coast fever. Transbound Emerg Dis. 67(Suppl. 1):56–67
Bishop R, Odongo D, Ahmed J, Mwamuye M, Fry L, Knowles D, Nanteza A, Lubega G, Gwakisa P, Clausen PH, Obara I
(See online at https://doi.org/10.1111/tbed.13325) - (2020). Antigen gene and variable number tandem repeat (VNTR) diversity in Theileria parva parasites from Ankole cattle in southwestern Uganda: evidence for conservation in antigen gene sequences combined with extensive polymorphism at VNTR loci. Transbound Emerg Dis. 67 (Suppl. 1):99–107
Nanteza A, Obara I, Kasaija P, Mwega E, Kabi F, Salih DA, Njahira M, Njuguna J, Odongo D, Bishop RP, Skilton RA, Ahmed J, Clausen PH, Lubega GW
(See online at https://doi.org/10.1111/tbed.13311) - (2020). Current status of tropical theileriosis in Northern Africa: a review of recent epidemiological investigations and implications for control. Transbound Emerg Dis. 67(Suppl. 1):8–25
Gharbi M, Darghouth M, Elati K, Al-Hosary A, Ayadi Q, Salih D, El Hussein A, Mhadhbi M, Khbou M, Hassan S, Obara I, Ahmed L, Ahmed J
(See online at https://doi.org/10.1111/tbed.13312) - (2020). First detection of Theileria parva in cattle from Cameroon in the absence of the main tick vector Rhipicephalus appendiculatus. Transbound Emerg Dis. 67(Suppl. 1):68–78
Silatsaa B, Simo G, Githaka N, Kamga R, Oumarou F, Keambou C, Machuka E, Domelevo J, Odongo D, Bishop R, Kuiate J, Njiokouh F, Djikeng A, Pelle R
(See online at https://doi.org/10.1111/tbed.13425) - (2020). Monitoring vaccinated cattle for induction and longevity of persistent tick transmissible infections: Implications for wider deployment of live vaccination against East Coast fever in Tanzania. Transbound Emerg Dis. 67(Suppl. 1):79–87
Gwakisa P, Mwega E, Kindoro F, Kimera S, Obara I, Ahmed J, Clausen PH, Bishop R
(See online at https://doi.org/10.1111/tbed.13405) - (2020). Multilocus genotyping of Theileria parva isolates associated with a live vaccination trial in Kenya provides evidence for transmission of immunizing parasites into local tick and cattle populations. Transbound Emerg Dis. 67(Suppl. 1):88–98.2019
Bishop RP, Odongo DO, Spooner PR, Morzaria SP, Oura CAL, Skilton RA
(See online at https://doi.org/10.1111/tbed.13417) - (2020). Serum-free in vitro cultivation of Theileria annulata and Theileria parva schizont-infected lymphocytes. Transbound Emerg Dis. 67(Suppl. 1):35–39
Zweygarth E, Nijhof A, Knorr S, Ahmed J, Al Hosary A, Obara I, Bishop R, Josemans A, Clausen PH
(See online at https://doi.org/10.1111/tbed.13348) - (2020). The protection afforded to cattle immunized with Theileria annulata infected cell line is enhanced by subunit vaccine candidate TaSP. Transbound Emerg Dis. 67(Suppl. 1):26–34
Saaid A, Salih D, Elhaj L, Abdalla M, Baumann M, Obara I, Ahmed J, Clausen PH, El Hussein A
(See online at https://doi.org/10.1111/tbed.13374) - (2020). Theileria annulata surface protein (TaSP) is a target of cyclin-dependent kinase 1 phosphorylation in Theileria annulatainfected cells. Transbound Emerg Dis. 67(Suppl. 1):40–55
Mackiewicz M, Seitzer U, Ahmed J, Reiling N
(See online at https://doi.org/10.1111/tbed.13458) - (2020). Towards wider and more efficient deployment of live vaccines for control of Theileria parva and Theileria annulata infections in cattle in eastern, central and northern Africa. Transbound Emerg Dis. 67(Suppl. 1):5–7
Obara I, Ahmed J, Bishop R, Clausen PH
(See online at https://doi.org/10.1111/tbed.13359)
