Genetic and antigenic variation of the bovine tick-borne pathogen Theileria parva in the Great Lakes region of Central Africa

Abstract

BackgroundTheileria parva causes East Coast fever (ECF), one of the most economically important tick-borne diseases of cattle in sub-Saharan Africa. A live immunisation approach using the infection and treatment method (ITM) provides a strong long-term strain-restricted immunity. However, it typically induces a tick-transmissible carrier state in cattle and may lead to spread of antigenically distinct parasites. Thus, understanding the genetic composition of T. parva is needed prior to the use of the ITM vaccine in new areas. This study examined the sequence diversity and the evolutionary and biogeographical dynamics of T. parva within the African Great Lakes region to better understand the epidemiology of ECF and to assure vaccine safety. Genetic analyses were performed using sequences of two antigen-coding genes, Tp1 and Tp2, generated among 119 T. parva samples collected from cattle in four agro-ecological zones of DRC and Burundi.ResultsThe results provided evidence of nucleotide and amino acid polymorphisms in both antigens, resulting in 11 and 10 distinct nucleotide alleles, that predicted 6 and 9 protein variants in Tp1 and Tp2, respectively. Theileria parva samples showed high variation within populations and a moderate biogeographical sub-structuring due to the widespread major genotypes. The diversity was greater in samples from lowlands and midlands areas compared to those from highlands and other African countries. The evolutionary dynamics modelling revealed a signal of selective evolution which was not preferentially detected within the epitope-coding regions, suggesting that the observed polymorphism could be more related to gene flow rather than recent host immune-based selection. Most alleles isolated in the Great Lakes region were closely related to the components of the trivalent Muguga vaccine.ConclusionsOur findings suggest that the extensive sequence diversity of T. parva and its biogeographical distribution mainly depend on host migration and agro-ecological conditions driving tick population dynamics. Such patterns are likely to contribute to the epidemic and unstable endemic situations of ECF in the region. However, the fact that ubiquitous alleles are genetically similar to the components of the Muguga vaccine together with the limited geographical clustering may justify testing the existing trivalent vaccine for cross-immunity in the region.

Sequence diversity of cytotoxic T cell antigens and satellite marker analysis of Theileria parva informs the immunization against East Coast fever in Rwanda

“…This clustering pattern could be as a result of recombination although the most highly probable reason could be due to the presence of mixed infection by different strains in the same animal. In contrast to a recent study [51], our study revealed the presence of three main clusters of cattle derived strains in Rwanda.…”

“…In addition, a high proportion of dS compared to dN coupled with 3 and 11 negative selection sites on Tp1 and Tp2, respectively and an absence of positive selection sites on both genes was indicative of the presence of purifying selection against change in dN as well as absence of selection pressure possibly attributed to the lack of vaccination programmes against ECF and/or the absence of tick control programmes. This, together with the radiating pattern observed on the MJ network further provides substantial evidence of a freely expanding population of T. parva with slightly similar genotypes to Muguga, Kiambu and Serengeti vaccine isolates in Rwanda, as has been reported in other regions [25,28,29,51,52].…”

“…Nyakizu showed high similarity with Muguga, Kiambu and Serengeti on all epitopes of Tp2. A high number of epitopes from field samples that were different from Muguga, Kiambu, Serengeti, Chitongo, Nyakizu and Gikongoro were also observed and this, coupled with a high nucleotide polymorphism of 15.9%, indicates the highly diverse and polymorphic nature of the Tp2 gene [25,28,29,51,52]. Phylogenetic analysis of Tp1 nucleotide sequences showed three clusters of cattle derived strains (Fig.…”

“…Furthermore, immunization against T. parva introduces carrier status in the immunized animals and these might also act as sources of future infection. In contrast to other studies [25,28,29,51,52], we extensively investigated the extent of sequence diversity, phylogenetic relationships and evolutionary dynamics of Tp1 and Tp2 genes coupled with satellite analysis using a panel of five satellite markers to determine the similarities among the field samples collected from Bugesera District of Rwanda and the Muguga, Kiambu, Serengeti, Chitongo, Gikongoro and Nyakizu vaccine isolates. The data generated from these analyses was then used to inform field challenge vaccine trials in Bugesera District, Rwanda.…”

Capture-based enrichment ofTheileria parvaDNA enables full genome assembly of first buffalo-derived strain and reveals exceptional intra-specific genetic diversity

“…However, ITM also has significant drawbacks, including a logistically intensive manufacturing process (reviewed in Di Giulio et al 2009). Also, there have been recently verified concerns that ITM is not always as effective against challenge from buffalo-derived T. parva as it is against cattle-derived parasites , and even cattle-derived T. parva from geographically diverse regions could sometimes break through immunity induced by the Muguga cocktail vaccine (Amzati et al 2019). The African buffalo (Syncerus caffer) is an asymptomatic wildlife carrier of T. parva in the region and is the primary mammalian host (Conrad et al 1987).…”