The biology of Theileria parva and control of East Coast fever – Current status and future trends

Abstract

Tremendous progress has been made over the last ten years on East Coast fever (ECF) research. Publication of a reference genome sequence of Theileria parva, the causative agent of ECF, has led to a more thorough characterization of the genotypic and antigenic diversity of the pathogen. It also facilitated identification of antigens that are targets of bovine major histocompatibility complex class I restricted cytotoxic T-lymphocytes (CTLs), induced by a live parasite-based infection and treatment method (ITM) vaccine. This has led to improved knowledge of epitope-specific T-cell responses to ITM that most likely contribute to the phenomenon of strain-specific immunity. The Muguga cocktail ITM vaccine, which provides broad-spectrum immunity to ECF is now a registered product in three countries in eastern Africa. Effort is directed at improving and scaling up the production process to make this vaccine more widely available on a commercial basis in the region. Meanwhile, research to develop a subunit vaccine based on parasite neutralizing antibodies and CTLs has been revived through convening of a research consortium to develop proof-of-concept for a next generation vaccine. Many new scientific and technical advances are facilitating this objective. Hence, the next decade promises even more progress toward an improved control of ECF.

Late-Stage C–H Alkylation of Heterocycles and 1,4-Quinones via Oxidative Homolysis of 1,4-Dihydropyridines

“…The latter is employed for the treatment of theileriosis, a cattle disease that represents an important threat to livestock production in Africa, generating losses above $200 million annually. 35 Alternatively, Atovaquone (an anti-malarial drug that acts by inhibiting the mitochondrial electron transport system and marketed as Malarone ® when combined with proguanil hydrochloride), 36 could be synthesized in a 54% yield as a kinetic mixture of diastereomers that could be easily converted to the more active trans -Atovaquone under acidic conditions. 31a Importantly, previous syntheses of Atovaquone based on a radical alkylation approach relied on the use of silver salts, significantly increasing the total cost of such a synthetic route.…”

Approaches to vaccination against Theileria parva and Theileria annulata

“…The impact of genome size variations on parasite gene content and biology, however, remains to be fully documented. Such data are beginning to accumulate for T. parva as more strains are sequenced and their impact on genotypic diversity has been briefly reviewed elsewhere …”

New approaches and omics tools for mining of vaccine candidates against vector-borne diseases

“…49 Despite rapid advances in the diagnosis of bacterial infections and the availability of effective antibiotics, Lyme disease, the most common vector borne disease, continues to represent a substantial public and global health problem. One antigen, termed Tp2, was identified by CTL from 4 different animals.…”