Browsing by Author "Lugelo, A."
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Item Alcelaphine herpesvirus-1 (Malignant Catarrhal Fever Virus) in wildebeest placenta: Genetic variation of ORF50 and A9.5 alleles(PLoS ONE, 2015-05-13) Lankester, F.; Lugelo, A.; Mnyambwa, N.; Ndabigaye, A.; Keyyu, J.; Kazwala, R. R.; Grant, D. M.; Relf, V.; Haig, D. M.; Cleaveland, S.; Russell, G. C.Alcelaphine herpesvirus–1 (AlHV-1), a causative agent of malignant catarrhal fever in cattle, was detected in wildebeest (Connochaetes taurinus) placenta tissue for the first time. Although viral load was low, the finding of viral DNA in over 50%of 94 samples tested lends support to the possibility that placental tissue could play a role in disease transmission and that wildebeest calves are infected in utero. Two viral loci were sequenced to examine variation among virus samples obtained from wildebeest and cattle: the ORF50 gene, encoding the lytic cycle transactivator protein, and the A9.5 gene, encoding a novel polymorphic viral glycoprotein. ORF50 was well conserved with six newly discovered alleles differing at only one or two base positions. In contrast, while only three new A9.5 alleles were discovered, these differed by up to 13% at the nucleotide level and up to 20% at the amino acid level. Structural homology searching performed with the additional A9.5 sequences determined in this study adds power to recent analysis identifying the four-helix bundle cytokine interleukin-4 (IL4) as themajor homologue. The majority of MCF virus samples obtained from Tanzanian cattle and wildebeest encoded A9.5 polypeptides identical to the previously characterized A9.5 allele present in the laboratory maintained AlHV-1 C500 strain. This supports the view that AlHV-1 C500 is suitable for the development of a vaccine for wildebeest-associated MCF.Item Comparing methods of assessing dog rabies vaccination coverage in rural and urban communities in Tanzania(Frontiers in Veterinary Science, 2017) Sambo, M.; Johnson, P.; Hotopp, K.; Changalucha, J.; Cleaveland, S.; Kazwala, R.; Lembo, T.; Lugelo, A.; Lushasi, K.; Maziku, M.Rabies can be eliminated by achieving comprehensive coverage of 70% of domestic dogs during annual mass vaccination campaigns. Estimates of vaccination coverage are, therefore, required to evaluate and manage mass dog vaccination programs; however, there is no specific guidance for the most accurate and efficient methods for estimating coverage in different settings. Here, we compare post-vaccination transects, school-based surveys, and household surveys across 28 districts in southeast Tanzania and Pemba island covering rural, urban, coastal and inland settings, and a range of different livelihoods and religious backgrounds. These approaches were explored in detail in a single district in northwest Tanzania (Serengeti), where their performance was compared with a complete dog population census that also recorded dog vaccination status. Post-vaccination transects involved counting marked (vaccinated) and unmarked (unvaccinated) dogs immediately after campaigns in 2,155 villages (24,721 dogs counted). School-based surveys were administered to 8,587 primary school pupils each representing a unique household, in 119 randomly selected schools approximately 2 months after campaigns. Household surveys were conducted in 160 randomly selected villages (4,488 households) in July/August 2011. Costs to implement these coverage assessments were $12.01, $66.12, and $155.70 per village for post- vaccination transects, school-based, and household surveys, respectively. Simulations were performed to assess the effect of sampling on the precision of coverage estimation. The sampling effort required to obtain reasonably precise estimates of coverage from household surveys is generally very high and probably prohibitively expensive for routine monitoring across large areas, particularly in communities with high human to dog ratios. School-based surveys partially overcame sampling constraints, however, were also costly to obtain reasonably precise estimates of coverage. Post-vaccination transects provided precise and timely estimates of community-level coverage that could be used to troubleshoot the performance of campaigns across large areas. However, transects typically overestimated coverage by around 10%, which therefore needs consideration 2 Sambo et al. Assessing Dog Rabies Vaccination Coverage Frontiers in Veterinary Science | www.frontiersin.org March 2017 | Volume 4 | Article 33 inTrODUcTiOn Rabies is a fatal viral disease transmitted to humans by animal bites, usually from domestic dogs. Although under control in most industrialized countries, rabies continues to kill an estimated 59,000 people each year in low- and middle-income countries (LMICs) (1). Reliable estimates of the proportion of dogs vaccinated against rabies are crucial to determine the performance of vaccination programs and their impact on disease transmission. Empirical and theoretical evidence shows that mass dog vaccination campaigns that reach at least 70% of the dog population can control rabies (2, 3). While achieving this coverage in all communities can lead to elimination, even small gaps in coverage can delay the time to elimination (4). As progress is made toward reaching global targets of zero human rabies deaths from dog-mediated rabies through the implementation of mass dog vaccinations (5), there is a clear need to identify reliable, cost-effective, and feasible approaches that can be used, at scale, to assess community-level vaccination coverage. Limited population data on owned and free-roaming dogs in most LMICs make estimation of vaccination coverage challenging. Several methods have been used to estimate coverage including (i) the use of pre-campaign estimates of dog population size through human to dog ratios (HDRs) as the denominator, and the number of dogs vaccinated during the campaign as the numerator (6); (ii) post-vaccination household surveys to estimate the proportion of vaccinated dogs (7–11); and (iii) post-vaccination transects to estimate the proportion of marked (vaccinated) dogs (4, 12–14). However, these methods all have limitations. If dog populations are estimated from data on HDRs, inaccuracies in estimates of the human population will invariably affect the accuracy of dog population estimates. This may occur, for example, through errors in extrapolating current human population sizes from census data (for example, using average population growth rates) or from administrative/boundary changes that affect village demarcations across different time periods. Furthermore, published data on HDRs usually reflect a sample from surveys across several communities (15), and even a small degree of variation in HDRs can have a major effect on dog population estimates at the community level. Household surveys are restricted to capturing estimates of vaccination coverage in owned dog populations and are relatively intensive to complete. Moreover, there is known to be wide variability in patterns of dog ownership within communities—for example, in Tanzania, a much smaller proportion of Muslim and urban households own dogs in comparison with rural, livestockkeeping communities (15). This variability and the highly skewed pattern of dog ownership in some communities make household surveys prone to selection and measurement biases (16). Additional uncertainty from household surveys arises in relation to validation of dog vaccination status. In Tunisia, for example, about 14% of dog owners who claimed their dogs were vaccinated were unable to provide certificates (17). Post-vaccination transects are limited to observations of freeroaming dogs and will, therefore, be biased toward dogs that are more likely to be observed from transects. For example, young puppies are likely to be less visible and are known to represent an age group that typically has a low vaccination coverage (9, 18, 19), thus resulting in the potential for overestimating coverage. In a recent study from Tanzania, post-vaccination transects were shown to overestimate coverage by approximately 7% in comparison with household surveys, although it was unclear in this study which of the approaches was most accurate (19). Here, we present a detailed assessment of three methods to estimate dog vaccination coverage across settings in Tanzania. We use a complete household census as reference data for a simulation experiment to determine the impacts of sampling on the precision of coverage estimates. Specifically, we aim to answer the following questions: (i) What are the resources (personnel, time, and money) required to implement these methods? (ii) Which methods provide the most precise estimates of coverage? and finally (iii) Which approaches, therefore, generate acceptable coverage estimates to provide operational guidance to improve the performance of current or future campaigns? MaTerials anD MeThODs study sites The study was conducted in 29 districts across Tanzania: 24 districts from southeast Tanzania, 4 districts from Pemba island, and 1 district (Serengeti district) from northwest Tanzania (Figure 1). These areas are inhabited by an estimated 9.1 million people (20% of the Tanzanian population) according to the 2012 national census (20) and represent districts that span a wide range of settings, comprising rural, urban, coastal and inland areas, and a range of livelihoods and religious backgrounds. Mass dog vaccination campaigns were conducted in all these districts by local government teams, with support of WHO and collaborating institutions. Various methods of estimating vaccination coverages achieved during campaigns were compared. Table 1 summarizes the methods used in different locations and the rationale for data collection. Post-Vaccination Transects To generate rapid estimates of village-level vaccination coverage, post-vaccination transects were conducted on the same day as when evaluating the impacts of campaigns. We discuss the advantages and disadvantages of these different methods and make recommendations for how vaccination campaigns can be better monitored and managed at different stages of rabies controlItem The efficacy of alcelaphine herpesvirus-1 (AlHV-1) immunization with the adjuvants Emulsigen and the monomeric TLR5 ligand FliC in zebu cattle against AlHV-1 malignant catarrhal fever induced by experimental virus challenge(Veterinary Microbiology, 2016-11-15) Lankester, F.; Lugelo, A.; Werling, D.; Mnyambwa, N.; Keyyu, J.; Kazwala, R.; Grant, D.; Smith, S.; Parameswaran, N.; Cleaveland, S.; Russell, G.; Haig, D.Malignant catarrhal fever (MCF) is a fatal disease of cattle that, in East Africa, follows contact with wildebeest excreting alcelaphine herpesvirus 1 (AlHV-1). Recently an attenuated vaccine (atAlHV-1) was tested under experimental challenge on Friesian-Holstein (FH) cattle and gave a vaccine efficacy (VE) of approximately 90%. However testing under field conditions on an East African breed, the shorthorn zebu cross (SZC), gave a VE of 56% suggesting that FH and SZC cattle may respond differently to the vaccine. To investigate, a challenge trial was carried out using SZC. Additionally three adjuvant combinations were tested: (i) Emulsigen®, (ii) bacterial flagellin (FliC) and (iii) Emulsigen® + bacterial flagellin. We report 100% seroconversion in all immunized cattle. The group inoculated with atAlHV-1 + Emulsigen® had significantly higher antibody titres than groups inoculated with FliC, the smallest number of animals that became infected and the fewest fatalities, suggesting this was the most effective combination. A larger study is required to more accurately determine the protective effect of this regime in SZC. There was an apparent inhibition of the antibody response in cattle inoculated with atAlHV-1 + FliC, suggesting FliC might induce an immune suppressive mechanism. The VE in SZC (50 – 60%) was less than that in FH (80 – 90%). We speculate that this might be due to increased risk of disease in vaccinated SZC (suggesting that the vaccine may be less effective at stimulating an appropriate immune response in this breed) and/or increased survival in unvaccinated SZC (suggesting that these cattle may have a degree of prior immunity against infection with AlHV-1).Item A field vaccine trial in Tanzania demonstrates partial protection against malignant catarrhal fever in cattle(ELSEVIER, 2015) Lankester, F.; Russell, G. C.; Lugelo, A.; Ndabigaye, A.; Mnyambwa, N.; Keyyu, J.; Kazwala, R. R.; Grant, D; Percival, A.; Deane, D.; Haig, D. M.; Cleaveland, S.Malignant catarrhal fever (MCF) is a fatal lymphoproliferative disease of cattle that, in East Africa, results from transmission of the causative virus, alcelaphine herpesvirus 1 (AlHV-1), from wildebeest. A vaccine field trial involving an attenuated AlHV-1 virus vaccine was performed over two wildebeest calving seasons on the Simanjiro Plain of northern Tanzania. Each of the two phases of the field trial consisted of groups of 50 vaccinated and unvaccinated cattle, which were subsequently exposed to AlHV-1 challenge by herding toward wildebeest. Vaccination resulted in the induction of virus-specific and virus-neutralizing antibodies. Some cattle in the unvaccinated groups also developed virus-specific antibody responses but only after the start of the challenge phase of the trial. PCR of DNA from blood samples detected AlHV-1 infection in both groups of cattle but the frequency of infection was significantly lower in the vaccinated groups. Some infected animals showed clinical signs suggestive of MCF but few animals went on to develop fatal MCF, with similar numbers in vaccinated and unvaccinated groups. This study demonstrated a baseline level of MCF-seropositivity among cattle in northern Tanzania of 1% and showed that AlHV-1 virus-neutralizing antibodies could be induced in Tanzanian zebu shorthorn cross cattle by our attenuated vaccine, a correlate of protection in previous experimental trials. The vaccine reduced infection rates by 56% in cattle exposed to wildebeest but protection from fatal MCF could not be determined due to the low number of fatal cases.