The impact and control of malignant catarrhal fever in Tanzania

Malignant Catarrhal Fever (MCF), an often-lethal infectious disease, presents as a variable complex of lesions in susceptible ungulate species. The disease is caused by a -herpesvirus following transmission from an inapparent carrier host. Two major epidemiological forms exist: wildebeest-associated MCF (WA-MCF), in which the virus is transmitted to susceptible species by wildebeest calves less than approximately four months of age, and sheepassociated MCF (SA-MCF) in which the virus is spread by sheep (primarily adolescents). Due to the lack of an in-vitro propagation system for the causative agent of the more economically significant SA-MCF, and with the expectation that cross-protective immunity may be provided, vaccine development has focused on the more easily propagated alcelaphine herpesvirus-1 (AlHV-1) that causes WA-MCF. In 2008 a direct viral challenge trial showed that a novel vaccine, employing an attenuated AlHV-1 (atAlHV-1) `C5000 virus strain, protected British Friesian-Holstein (FH) cattle against an intranasal challenge with virulent AlHV-1 `C5000 virus. For cattle keeping people living near wildebeest calving areas in sub-Saharan Africa an effective vaccine would have value as it would release them from the costly annual disease avoidance strategy of having to move their herds away from the oncoming wildebeest. On the other hand, an effective vaccine will release herd owners from the need to avoid MCF, allowing them to graze their cattle alongside wildebeest on the highly nutritious pastures of the calving areas. As such conservationists have raised concerns that the development of a vaccine might lead to detrimental grazing competition. The principle objective of this study was to test the novel vaccine on Tanzanian shorthorn zebu cross cattle (SZC).We did this firstly using a natural challenge field trial (Chapter Two) which demonstrated that immunisation with the atAlHV-1 vaccine was well tolerated and induced an oro-nasopharyngeal AlHV-1-specific and -neutralising antibody response. This resulted in an immunity in SZC cattle that was partially protective and reduced naturally transmitted infection by 56%. We also demonstrated that non-fatal infections occurred with a much higher frequency than previously thought. Because the calculated efficacy of the vaccine was less than that seen in British FH cattle we wanted to determine whether host factors, particular to SZC cattle, had impacted the outcomes of the field trial. To do this we repeated the 2008 direct viral challenge trial using SZC cattle (Chapter Four). During this trial we also investigated whether the recombinant bacterial flagellin monomer (FliC), when used as an adjuvant, might improve the vaccine’s efficacy. The findings from this trial indicated that direct challenge with pathogenic AlHV-1 is effective at inducing MCF in SZC cattle and that FliC is not an appropriate adjuvant for this vaccine. Furthermore, with less control group cattle dying of MCF than expected we speculate that SZC cattle may have a degree of resistance to MCF that affords them protection from infection and developing fatal disease. In Chapter Three we investigated aspects of the epidemiology of MCF, specifically whether wildebeest placenta, long implicated by Maasai cattle owners as a source of MCF, might play a role in viral transmission. Additionally, through comparative sequence analysis, at two specific genes (A9.5 and ORF50) of wild-type and atAlHV-1, we investigated whether the `C5000 strain, the source of which was taken from Africa more than 40 years ago, was appropriate for vaccine development. The detection of AlHV-1 virus in approximately 50% of placentae indicated that infection can occur in-utero and that this tissue might play a role in disease transmission. And, despite describing three new alleles of the A9.5 gene (supporting previous evidence that this gene is polymorphic and encodes a secretory protein with interleukin-4 as the major homologue), the observation that the most frequently detected haplotypes, in both wild-type and attenuated AlHV-1, were identical suggests that AlHV-1 has a slow molecular clock and that the attenuated strain was appropriate for vaccine development. In Chapter Five we present the first quantitative assessment of the annual MCF avoidance costs that Maasai pastoralists incur. In particular we estimated that as a result of MCF avoidance 64% of the total daily milk yield during the MCF season was not available to be used by the 81% of the family unit remaining at the permanent boma. This represents an upper-bound loss of approximately 8% of a household0s annual income. Despite these considerable losses we concluded that, given an incidence of fatal MCF in cattle living in wildebeest calving areas of 5% to 10%, if herd owners were to stop trying to avoid MCF by allowing their cattle to graze alongside wildebeest, any gains made through increased availability of milk, improved body condition and reduced energy demands would be offset by an increase in MCF-incidence. With the development of an effective vaccine, however, this alternative strategy might become optimal. The overall conclusion we draw therefore is that, despite the substantial costs incurred each year avoiding MCF, the partial protection afforded by the novel vaccine strategy is not sufficient to warrant a wholesale change in disease avoidance strategy. Nonetheless, even the partial protection provided by this vaccine could be of value to protect animals that cannot be moved, for example where some of the herd remain at the boma to provide milk or where land-use changes make traditional disease avoidance difficult. Furthermore, the vaccine may offer a feasible solution to some of the current land-use challenges and conflicts, providing a degree of protection to valuable livestock where avoidance strategies are not possible, but with less risk of precipitating the potentially damaging environmental consequences, such as overgrazing of highly nutritious seasonal pastures, that might result if herd owners decide they no longer need to avoid wildebeest

Economic Burden of Livestock Abortions in Northern Tanzania

This research article was published by Cambridge University Press,2024Livestock abortion is a source of economic loss for farmers, but its economic impact has not been estimated in many Low and Middle-Income Countries. This article presents an estimation methodology and estimates for the gross and net cost of an abortion based on a sample of livestock-owning households in three regions of northern Tanzania and market data. We then generate aggregate estimates of abortion losses across Tanzania. We estimate annual gross and net annual losses of about $263 Million (about TZS 600 billion) and$131 million (about TZS 300 billion), respectively

The sero-epidemiology of Neospora caninum in cattle in northern Tanzania

Neospora caninum is a protozoan intracellular parasite of animals with a global distribution. Dogs act as definitive hosts, with infection in cattle leading to reproductive losses. Neosporosis can be a major source of income loss for livestock keepers, but its impacts in sub-Saharan Africa are mostly unknown. This study aimed to estimate the seroprevalence and identify risk factors for N. caninum infection in cattle in northern Tanzania, and to link herd-level exposure to reproductive losses. Serum samples from 3,015 cattle were collected from 380 households in 20 villages between February and December 2016. Questionnaire data were collected from 360 of these households. Household coordinates were used to extract satellite derived environmental data from open-access sources. Sera were tested for the presence of N. caninum antibodies using an indirect ELISA. Risk factors for individual-level seropositivity were identified with logistic regression using Bayesian model averaging (BMA). The relationship between herd-level seroprevalence and abortion rates was assessed using negative binomial regression. The seroprevalence of N. caninum exposure after adjustment for diagnostic test performance was 21.5% [95% Credibility Interval (CrI) 17.9–25.4]. The most important predictors of seropositivity selected by BMA were age greater than 18 months [Odds ratio (OR) = 2.17, 95% CrI 1.45–3.26], the local cattle population density (OR = 0.69, 95% CrI 0.41–1.00), household use of restricted grazing (OR = 0.72, 95% CrI 0.25–1.16), and an increasing percentage cover of shrub or forest land in the environment surrounding a household (OR = 1.37, 1.00–2.14). There was a positive relationship between herd-level N. caninum seroprevalence and the reported within-herd abortion rate (Incidence Rate Ratio = 1.03, 95% CrI 1.00–1.06). Our findings suggest N. caninum is likely to be an important cause of abortion in cattle in Tanzania. Management practices, such as restricted grazing, are likely to reduce the risk of infection and suggest contamination of communal grazing areas may be important for transmission. Evidence for a relationship between livestock seropositivity and shrub and forest habitats raises questions about a potential role for wildlife in the epidemiology of N. caninum in Tanzania

MACHOS: Markov clusters of homologous subsequences

Motivation: The classification of proteins into homologous groups (families) allows their structure and function to be analysed and compared in an evolutionary context. The modular nature of eukaryotic proteins presents a considerable challenge to the delineation of families, as different local regions within a single protein may share common ancestry with distinct, even mutually exclusive, sets of homologs, thereby creating an intricate web of homologous relationships if full-length sequences are taken as the unit of evolution. We attempt to disentangle this web by developing a fully automated pipeline to delineate protein subsequences that represent sensible units for homology inference, and clustering them into putatively homologous families using the Markov clustering algorithm

The effect of cup outer sizes on the contact mechanics and cement fixation of cemented total hip replacements

One important loosening mechanism of the cemented total hip arthroplasty is the mechanical overload at the bone-cement interface and consequent failure of the cement fixation. Clinical studies have revealed that the outer diameter of the acetabular component is a key factor in influencing aseptic loosening of the hip arthroplasty. The aim of the present study was to investigate the influence of the cup outer diameter on the contact mechanics and cement fixation of a cemented total hip replacement (THR) with different wear penetration depths and under different cup inclination angles using finite element (FE) method. A three-dimensional FE model was developed based on a typical Charnley hip prosthesis. Two acetabular cup designs with outer diameters of 40 and 43 mm were modelled and the effect of cup outer diameter, penetration depth and cup inclination angle on the contact mechanics and cement fixation stresses in the cemented THR were studied. The results showed that for all penetration depths and cup inclination angles considered, the contact mechanics in terms of peak von Mises stress in the acetabular cup and peak contact pressure at the bearing surface for the two cup designs were similar (within 5%). However, the peak von Mises stress, the peak maximum principal stress and peak shear stress in the cement mantle at the bone-cement interface for the 43 mm diameter cup design were predicted to be lower compared to those for the 40 mm diameter cup design. The differences were predicted to be 15-19%, 15-22% and 18-20% respectively for different cup penetration depths and inclination angles, which compares to the clinical difference of aseptic loosening incidence of about 20% between the two cup designs

Resurrection and redescription of Varestrongylus alces (Nematoda; Protostrongylidae), a lungworm of the Eurasian moose (Alces alces), with report on associated pathology

Varestrongylus alces, a lungworm in Eurasian moose from Europe has been considered a junior synonym of Varestrongylus capreoli, in European roe deer, due to a poorly detailed morphological description and the absence of a type-series. Methods Specimens used in the redescription were collected from lesions in the lungs of Eurasian moose, from Vestby, Norway. Specimens were described based on comparative morphology and integrated approaches. Molecular identification was based on PCR, cloning and sequencing of the ITS-2 region of the nuclear ribosomal DNA. Phylogenetic analysis compared V. alces ITS-2 sequences to these of other Varestrongylus species and other protostrongylids. Results Varestrongylus alces is resurrected for protostrongylid nematodes of Eurasian moose from Europe. Varestrongylus alces causes firm nodular lesions that are clearly differentiated from the adjacent lung tissue. Histologically, lesions are restricted to the parenchyma with adult, egg and larval parasites surrounded by multinucleated giant cells, macrophages, eosinophilic granulocytes, lymphocytes. The species is valid and distinct from others referred to Varestrongylus, and should be separated from V. capreoli. Morphologically, V. alces can be distinguished from other species by characters in the males that include a distally bifurcated gubernaculum, arched denticulate crura, spicules that are equal in length and relatively short, and a dorsal ray that is elongate and bifurcated. Females have a well-developed provagina, and are very similar to those of V. capreoli. Morphometrics of first-stage larvae largely overlap with those of other Varestrongylus. Sequences of the ITS-2 region strongly support mutual independence of V. alces, V. cf. capreoli, and the yet undescribed species of Varestrongylus from North American ungulates. These three taxa form a well-supported crown-clade as the putative sister of V. alpenae. The association of V. alces and Alces or its ancestors is discussed in light of host and parasite phylogeny and host historical biogeography. Varestrongylus alces is a valid species, and should be considered distinct from V. capreoli. Phylogenetic relationships among Varestrongylus spp. from Eurasia and North America are complex and consistent with faunal assembly involving recurrent events of geographic expansion, host switching and subsequent speciation. Cervidae, Cryptic species, Historical biogeography, ITS-2, Metastrongyloidea, Parasite biodiversity, Varestrongylinae, Varestrongylus capreoli, Verminous pneumoniapublishedVersio

Inter-epidemic Rift Valley fever virus infection incidence and risks for zoonotic spillover in northern Tanzania

Rift Valley fever virus (RVFV) is a mosquito-borne pathogen that has caused epidemics involving people and animals across Africa and the Arabian Peninsula. A number of studies have found evidence for the circulation of RVFV among livestock between these epidemics but the population-level incidence of infection during this inter-epidemic period (IEP) is rarely reported. General force of infection (FOI) models were applied to age-adjusted cross-sectional serological data to reconstruct the annual FOI and population-level incidence of RVFV infection among cattle, goats, and sheep in northern Tanzania from 2009 through 2015, a period without reported Rift Valley fever (RVF) cases in people or animals. To evaluate the potential for zoonotic RVFV spillover during this period, the relationship between village-level livestock RVFV FOI and human RVFV seropositivity was quantified using multi-level logistic regression. The predicted average annual incidence was 72 (95% Credible Interval [CrI] 63, 81) RVFV infections per 10,000 animals and 96 (95% CrI 81, 113), 79 (95% CrI 62, 98), and 39 (95% CrI 28, 52) per 10,000 cattle, sheep, and goats, respectively. There was variation in transmission intensity between study villages, with the highest estimated village-level FOI 2.49% (95% CrI 1.89, 3.23) and the lowest 0.12% (95% CrI 0.02, 0.43). The human RVFV seroprevalence was 8.2% (95% Confidence Interval 6.2, 10.9). Human seropositivity was strongly associated with the village-level FOI in livestock, with the odds of seropositivity in an individual person increasing by around 1.2 times (95% CrI 1.1, 1.3) for each additional annual RVFV seroconversion per 1,000 animals. A history of raw milk consumption was also positively associated with human seropositivity. RVFV has circulated at apparently low levels among livestock in northern Tanzania in the period since the last reported epidemic. Although our data do not allow us to confirm human RVFV infections during the IEP, a strong association between human seropositivity and the FOI in cattle, goats, and sheep supports the hypothesis that RVFV circulation among livestock during the IEP poses a risk for undetected zoonotic spillover in northern Tanzania. We provide further evidence for the likely role of raw milk consumption in RVFV transmission from animals to people

Species Association of Hepatitis B Virus (HBV) in Non-Human Apes; Evidence for Recombination between Gorilla and Chimpanzee Variants

Hepatitis B virus (HBV) infections are widely distributed in humans, infecting approximately one third of the world's population. HBV variants have also been detected and genetically characterised from Old World apes; Gorilla gorilla (gorilla), Pan troglodytes (chimpanzee), Pongo pygmaeus (orang-utan), Nomascus nastusus and Hylobates pileatus (gibbons) and from the New World monkey, Lagothrix lagotricha (woolly monkey). To investigate species-specificity and potential for cross species transmission of HBV between sympatric species of apes (such as gorillas and chimpanzees in Central Africa) or between humans and chimpanzees or gorillas, variants of HBV infecting captive wild-born non-human primates were genetically characterised. 9 of 62 chimpanzees (11.3%) and two from 11 gorillas (18%) were HBV-infected (15% combined frequency), while other Old world monkey species were negative. Complete genome sequences were obtained from six of the infected chimpanzee and both gorillas; those from P. t .ellioti grouped with previously characterised variants from this subspecies. However, variants recovered from P. t. troglodytes HBV variants also grouped within this clade, indicative of transmission between sub-species, forming a paraphyletic clade. The two gorilla viruses were phylogenetically distinct from chimpanzee and human variants although one showed evidence for a recombination event with a P.t.e.-derived HBV variant in the partial X and core gene region. Both of these observations provide evidence for circulation of HBV between different species and sub-species of non-human primates, a conclusion that differs from the hypothesis if of strict host specificity of HBV genotypes

Tracing the origins of rescued chimpanzees reveals widespread chimpanzee hunting in Cameroon

<p>Abstract</p> <p>Background</p> <p>While wild chimpanzees are experiencing drastic population declines, their numbers at African rescue and rehabilitation projects are growing rapidly. Chimpanzees follow complex routes to these refuges; and their geographic origins are often unclear. Identifying areas where hunting occurs can help law enforcement authorities focus scarce resources for wildlife protection planning. Efficiently focusing these resources is particularly important in Cameroon because this country is a key transportation waypoint for international wildlife crime syndicates. Furthermore, Cameroon is home to two chimpanzee subspecies, which makes ascertaining the origins of these chimpanzees important for reintroduction planning and for scientific investigations involving these chimpanzees.</p> <p>Results</p> <p>We estimated geographic origins of 46 chimpanzees from the Limbe Wildlife Centre (LWC) in Cameroon. Using Bayesian approximation methods, we determined their origins using mtDNA sequences and microsatellite (STRP) genotypes compared to a spatial map of georeferenced chimpanzee samples from 10 locations spanning Cameroon and Nigeria. The LWC chimpanzees come from multiple regions of Cameroon or forested areas straddling the Cameroon-Nigeria border. The LWC chimpanzees were partitioned further as originating from one of three biogeographically important zones occurring in Cameroon, but we were unable to refine these origin estimates to more specific areas within these three zones.</p> <p>Conclusions</p> <p>Our findings suggest that chimpanzee hunting is widespread across Cameroon. Live animal smuggling appears to occur locally within Cameroon, despite the existence of local wildlife cartels that operate internationally. This pattern varies from the illegal wildlife trade patterns observed in other commercially valuable species, such as elephants, where specific populations are targeted for exploitation. A broader sample of rescued chimpanzees compared against a more comprehensive grid of georeferenced samples may reveal 'hotspots' of chimpanzee hunting and live animal transport routes in Cameroon. These results illustrate also that clarifying the origins of refuge chimpanzees is an important tool for designing reintroduction programs. Finally, chimpanzees at refuges are frequently used in scientific investigations, such as studies investigating the history of zoonotic diseases. Our results provide important new information for interpreting these studies within a precise geographical framework.</p