Browsing by Author "Cleaveland, S."
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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 Domestic dog demographic structure and dynamics relevant to rabies control planning in urban areas in Africa: The case of Iringa, Tanzania(BMC Veterinary Research, 2012) Gsell, A. S.; Knobel, D. L.; Cleaveland, S.; Kazwala, R. R.; Vounatsou, P.; Zinsstag, J.Background: Mass vaccinations of domestic dogs have been shown to effectively control canine rabies and hence human exposure to rabies. Knowledge of dog population demography is essential for planning effective rabies vaccination programmes; however, such information is still rare for African domestic dog populations, particularly so in urban areas. This study describes the demographic structure and population dynamics of a domestic dog population in an urban Sub-Saharan African setting. In July to November 2005, we conducted a full household-level census and a cross-sectional dog demography survey in four urban wards of Iringa Municipality, Tanzania. The achievable vaccination coverage was assessed by a two-stage vaccination campaign, and the proportion of feral dogs was estimated by a mark-recapture transect study. Results: The estimated size of the domestic dog population in Iringa was six times larger than official town records assumed, however, the proportion of feral dogs was estimated to account for less than 1% of the whole population. An average of 13% of all households owned dogs which equalled a dog:human ratio of 1:14, or 0.31 dogs per household or 334 dogs km-2. Dog female:male ratio was 1:1.4. The average age of the population was 2.2 years, 52% of all individuals were less than one year old. But mortality within the first year was high (72%). Females became fertile at the age of 10 months and reportedly remained fertile up to the age of 11 years. The average number of litters whelped per fertile female per year was 0.6 with an average of 5.5 pups born per litter. The population growth was estimated at 10% y-1. Conclusions: Such high birth and death rates result in a rapid replacement of anti-rabies immunised individuals with susceptible ones. This loss in herd immunity needs to be taken into account in the design of rabies control programmes. The very small proportion of truly feral dogs in the population implies that vaccination campaigns aimed at the owned dog population are sufficient to control rabies in urban Iringa, and the same may be valid in other, comparable urban settings.Item 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 Elucidating the phylodynamics of endemic rabies virus in eastern Africa using whole-genome sequencing(Virus Evolution, 2015) Brunker, K.; Marston, D. A.; Horton, D. L.; Cleaveland, S.; Fooks, A. R.; Kazwala, R. R.; Ngeleja, C.; Lembo, T.; Sambo, M; Mtema, Z. J.; Sikana, L.; Wilkie, G.; Biek, R.; Hampson, K.Many of the pathogens perceived to pose the greatest risk to humans are viral zoonoses, responsible for a range of emerging and endemic infectious diseases. Phylogeography is a useful tool to understand the processes that give rise to spatial patterns and drive dynamics in virus populations. Increasingly, whole-genome information is being used to uncover these patterns, but the limits of phylogenetic resolution that can be achieved with this are unclear. Here, whole-genome variation was used to uncover fine-scale population structure in endemic canine rabies virus circulating in Tanzania. This is the first whole-genome population study of rabies virus and the first comprehensive phylogenetic analysis of rabies virus in East Africa, providing important insights into rabies transmission in an endemic system. In addition, sub-continental scale patterns of population structure were identified using partial gene data and used to determine population structure at larger spatial scales in Africa. While rabies virus has a defined spatial structure at large scales, increasingly frequent levels of admixture were observed at regional and local levels. Discrete phylogeographic analysis revealed long-distance dispersal within Tanzania, which could be attributed to human-mediated movement, and we found evidence of multiple persistent, co-circulating lineages at a very local scale in a single district, despite on-going mass dog vaccination campaigns. This may reflect the wider endemic circulation of these lineages over several decades alongside increased admixture due to humanmediated introductions. These data indicate that successful rabies control in Tanzania could be established at a national level, since most dispersal appears to be restricted within the confines of country borders but some coordination with neighbouring countries may be required to limit transboundary movements. Evidence of complex patterns of rabies circulation within Tanzania necessitates the use of whole-genome sequencing to delineate finer scale population structure that can that can guide interventions, such as the spatial scale and design of dog vaccination campaigns and dog movement controls to achieve and maintain freedom from disease.Item The feasibility of canine rabies elimination in Africa: Dispelling doubts with data(2010-02-23) Lembo, T.; Hampson, K.; Kaare, M. T.; Ernest, E.; Knobel, D.; Kazwala, R. R.; Haydon, D. T.; Cleaveland, S.Background: Canine rabies causes many thousands of human deaths every year in Africa, and continues to increase throughout much of the continent. Methodology/Principal Findings: This paper identifies four common reasons given for the lack of effective canine rabies control in Africa: (a) a low priority given for disease control as a result of lack of awareness of the rabies burden; (b) epidemiological constraints such as uncertainties about the required levels of vaccination coverage and the possibility of sustained cycles of infection in wildlife; (c) operational constraints including accessibility of dogs for vaccination and insufficient knowledge of dog population sizes for planning of vaccination campaigns; and (d) limited resources for implementation of rabies surveillance and control. We address each of these issues in turn, presenting data from field studies and modelling approaches used in Tanzania, including burden of disease evaluations, detailed epidemiological studies, operational data from vaccination campaigns in different demographic and ecological settings, and economic analyses of the cost-effectiveness of dog vaccination for human rabies prevention. Conclusions/Significance: We conclude that there are no insurmountable problems to canine rabies control in most of Africa; that elimination of canine rabies is epidemiologically and practically feasible through mass vaccination of domestic dogs; and that domestic dog vaccination provides a cost-effective approach to the prevention and elimination of human rabies deaths.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.Item A field vaccine trial in Tanzania demonstrates partial protection against malignant catarrhal fever in cattle(Elsevier, 2016) Lankester, F; Lugelo, A; Ndabigaye, A; Mnyambwa, N; Keyyu, J.; Kazwala, R.; Grant, D; Percival, A.; Deane, D; Haig, D.M.; Cleaveland, S.; Russell, G. C.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.Item Genetic profile of Mycobacterium tuberculosis and treatment outcomes in human pulmonary tuberculosis in Tanzania(Tanzania Journal of Health Research, 2014-04-02) Mfinanga, S. G. M.; Warren, R. M.; Kazwala, R. R.; Kahwa, A.; Kazimoto, T.; Kimaro, G.; Mfaume, S.; Chonde, T.; Ngadaya, E.; Egwaga, S.; Streicher, E. M.; Van Pittius, G. N. C.; Morkve, O.; Cleaveland, S.Information on the different spoligotype families of Mycobacterium tuberculosis in Tanzania is limited, and where available, restricted to small geographical areas. This article describes the genetic profile of M. tuberculosis across Tanzania and suggests how spoligotype families might affect drug resistance and treatment outcomes for smear positive pulmonary tuberculosis patients in Tanzania. We conducted the study from 2006 to 2008, and the isolates were obtained from samples collected under the routine drug resistance surveillance system. The isolates were from specimens collected from 2001 to 2007, and stored at the Central and Reference Tuberculosis Laboratory. A total of 487 isolates from 23 regions in the country were spoligotyped. We were able to retrieve clinical information for 446 isolates only. Out of the 487 isolates spoligotyped, 195(40.0%) belonged to the Central Asian (CAS) family, 84 (17.5%) to the Latin American Mediterranean (LAM) family, 49 (10.1%) to the East-African Indian (EAI) family, and 33 (6.8%) to the Beijing family. Other isolates included 1 (0.2%) for H37Rv, 10 (2.1%) for Haarlem, 4 (0.8%) for S family, 58 (11.9%) for T family and 52 (10.7%) for unclassified. No spoligotype patterns were consistent with M. bovis. Regarding treatment outcomes, the cure rate was 80% with no significant variation among the spoligotype families. The overall level of MDR TB was 2.5% (3/121), with no significant difference among the spoligotype families. All Beijing strains (11.8%, 30/254) originated from the Eastern and Southern zones of the country, of which 80% were from Dar es Salaam. Isolates from the CAS and T families were reported disproportionately from the Eastern-Southern zone, and EAI and LAM families from the Northern-Lake zones but the difference was not statistically significant. Five isolates were identified as non-tuberculous Mycobacteria. In conclusion, M. tuberculosis isolates from pulmonary tuberculosis cases in Tanzania were classified mostly within the CAS, LAM, and EAI and T families, while the Beijing family comprised about 7% isolates only. Consistently good treatment outcomes were recorded across these spoligotype families. The proportion of drug resistance strains was low. The findings also suggest variation of spoligotype families with varying geographical localities within the country, and identify this area for further research to confirm this finding.Item Mobile phones as surveillance tools: Implementing and evaluating a large-scale intersectoral surveillance system for rabies in Tanzania(PLOS Medicine, 2016-04-12) Mtema, Z.; Changalucha, J.; Cleaveland, S.; Elias, M.; Ferguson, M. H.; Halliday, J. E. B.; Haydon, D.T.; Jaswant, G.; Kazwala, R. R.; Killeen, G. F.; Lembo, T; Lushasi, K.; Malishee, A. D.; Mancy, R.; Maziku, M.; Mbunda, E. M.; Mchau, G. J. M.; Murray-Smith, R.; Rysava, K.; Said, K.; Sambo, M.; Shayo, E.; Sikana, L.; Townsend, S. E.; Urassa, H.; Hampson, K.Surveillance is critical to manage preventative health services and control infectious diseases. Integrated surveillance involving public health, veterinary, and environmental sectors is urgently needed to effectively manage zoonoses and vector-borne diseases. However, most surveillance in low-income countries is paper-based, provides negligible timely feedback, is poorly incentivised, and results in delays, limited reporting, inaccurate data, and costly processing. • The potential of mobile technologies for improving health system surveillance has been demonstrated through small-scale pilots, but large-scale evaluations under programmatic implementation remain rare. • An intersectoral mobile-phone–based system was developed and implemented for rabies surveillance across southern Tanzania. Since 2011, the system has facilitated near realtime reporting of animal bites and human and animal vaccine use (almost 30,000 reports) by over 300 frontline health and veterinary workers across a catchment area of 150,000 km2 with >10 million inhabitants, improving data quality, timeliness, and completeness while reducing costs. • The surveillance system infrastructure is a platform that can be further developed to improve services and deliver health interventions; for example, generating automated personalized text messages (SMS) to alert patients to their vaccination schedules improved their compliance with regimens. Other interventions targeting patients and health workers can now be implemented easily. • The system has become an integrated, popular, and valuable tool across sectors, used routinely throughout southern Tanzania to evaluate the impacts of rabies control and prevention activities and to improve their management, directly informed by the experiences of frontline users. • We discuss challenges encountered during development and deployment, how we overcame these, and our recommendations for scaling up mobile-phone–based health (mHealth) interventions in low-income countries.Item Mycobacterial adenitis: role of mycobacterium bovis, non-tuberculous mycobacteria, hiv infection, and risk factors in arusha, Tanzania(East African Medical Journal, 2004-04) Mfinanga, S .G .M.; Morkve, O.; Kazwala, R. R.; Cleaveland, S.; Sharp, M. J.; Kunda, J.; Nilsen, R.Objective: To assess risk factors and mycobacterial agents in mycobacterial adenitis. Design: Cross sectional involving comparison analysis of high-risk groups. Setting: Seven hospitals in rural and semi-rural districts of Arusha. Subjects: The study comprised of 457 patients of clinically diagnosed mycobacterial adenitis. Interventions: Biopsy materials were cultured and identification of mycobacterial isolates, and HIV infection testing were performed using standard methods. A questionnaire was used to establish information for assessing risk factors. Main outcome measures: Proportions of mycobacterial isolates, risk factors and odds ratios. Results: Of the 457 specimens, 65(14.2%) were culture positive. Isolates identified were M. bovis, 7(10.8%) M. tuberculosis, 27(41.5%) and non-tuberculous mycobacteria 31(47.7%). HIV infection and ingestion of raw milk were linked with increased risk of M. bovis infection by OR of 13.6 (95% CI, 1.7 - 109.9) and 15.28 (3.26 - 71.7), respectively. On multivariate analysis, an OR of 16.2 (1.3 - 201.3) for having M. bovis adenitis was linked to HIV infection, raw milk and houses with poor ventilation. An OR of 5.2 (1.2 - 20.6) for non-tuberculous mycobacterial adenitis was linked to history of TB in the family, HIV infection, raw milk, raw animal products and poor knowledge on transmission of tuberculosis. Conclusions: M. bovis caused one out of ten cases of culture positive mycobacterial adenitis. Non-tuberculous mycobacteria were more common than M. tuberculosis (50% and 40% of the cases, respectively). HIV infection and raw animal products are among the risk factors identified for M. bovis and non-tuberculous mycobacterial adenitis.Item Mycobacterium bovis in rural Tanzania: Risk factors for infection in human and cattle populations(Tuberculosis, 2006-01-13) Cleaveland, S.; Shawa, D. J.; Mfinangac, S. G.; Shirimad, G.; Kazwalae, R. R.; Eblate, E.; Sharp, M.Although bovine tuberculosis is widespread throughout Africa, very little is known about risk factors for Mycobacterium bovis infection in either human or cattle populations. A human case–control study was conducted in northern Tanzania, comparing risk factors and prevalence of cattle interdermal test positives of cases (cervical adenitis cases from which M. bovis was isolated) with age- and sexmatched controls (selected at random from potential hospital attendees within the community). A cattle cross-sectional study was also set-up involving 27 villages selected at random in four districts, with 10,549 cattle and 622 herds tested, and questionnaire surveys conducted in 239 households. M. bovis was confirmed in seven of 65 (10.8%) human cervical adenitis cases, of which only one came from a household owning infected cattle. M. bovis in human patients was associated with families in which a confirmed diagnosis of tuberculosis had previously been made (po0:001) and with households far (4100 m) from neighbours (p ¼ 0:003). In cattle, overall prevalence of intradermal test positives was low at 0.9% (0.70–1.06%), but widespread, with 11.8% (8.44–13.17%) herds containing at least one reactor. Prevalence of intradermal test positives increased significantly with cattle age (po0:001). Herds with the following risk factors had a significantly greater prevalence of intradermal test positives: 450 cattle in the herd (p ¼ 0:024); herds housed inside at night (p ¼ 0:021) and herds in contact with wildlife (p ¼ 0:041). Furthermore, villages that experienced annual flooding had a higher prevalence of infection (p ¼ 0:043).Item Prevalence of echinococcosis in dogs and wild carnivores in selected Serengeti ecosystem areas of Tanzania(African Journal Online, 2013-05-15) Eblate, E.; Nonga, H. E.; Cleaveland, S.A prevalence study on echinococcosis in dogs and wild carnivores was conducted in northen Tanzania. Copro-antigen ELISA was used to screen 442 dog faecal samples from Magu, Bariadi and Ngorongoro districts, together with 88 wild carnivore samples from Serengeti National Park. Overall prevalence of E. granulosus in dogs was 12.4%. Magu (14.6%) and Ngorongoro districts (10.0%) had higher prevalence than Bariadi district (6.3%). The prevalence of echinococcosis in wild carnivores was 13.6%. Species which were positive to Copro-antigen ELISA test included bat eared fox (Otocyon megalotis) (14.3%), cheetah (Acinonyx jubatus) (16.1%), spotted hyaena (Crocuta crocuta) (37.5%) and lion (Panthera leo) (10.0%). The findings uncover that dogs and wild carnivores from northern Tanzania are infected with E. granulosus, a situation which may pose a risk of infection to other hosts including human. Therefore, more epidermiological investigation is needed to understand the dynamics of the disease in human, domestic animals and wildlife.Item Progress towards rabies elimination from Pemba Island, Southern Tanzania.(Online Journal of Public Health Informatics ., 2017) Lushasi, K. S.; Cleaveland, S.; Changalucha, J. J.; Haydon, D.; Kazwala, R.; Lembo, T.; Masoud, M.; Maziku, M.; Mchau, G.; Mtema, Z.; Omar, K.; Maganga, S.; Rysava, K.; Hampson, K.Using active surveillance approaches to investigate the transmission dynamics of rabies on Pemba Island and across Southern Tanzania, whilst a large-scale dog vaccination program was underway1 , to gain a greater understanding of the dynamics of infection as the disease is driven towards eliminationItem Quantifying risk factors for human brucellosis in rural northern Tanzania(PLoS ONE, 2010-04-01) John, K.; Fitzpatrick, J.; French, N.; Kazwala, R.; Kambarage, D.; Mfinanga, G. S.; MacMillan, A.; Cleaveland, S.Background: Brucellosis is a zoonosis of veterinary, public health and economic significance in most developing countries. Human brucellosis is a severely debilitating disease that requires prolonged treatment with a combination of antibiotics. The disease can result in permanent and disabling sequel, and results in considerable medical expenses in addition to loss of income due to loss of working hours. A study was conducted in Northern Tanzania to determine the risk factors for transmission of brucellosis to humans in Tanzania. Methods: This was a matched case-control study. Any patient with a positive result by a competitive ELISA (c-ELISA) test for brucellosis, and presenting to selected hospitals with at least two clinical features suggestive of brucellosis such as headache, recurrent or continuous fever, sweating, joint pain, joint swelling, general body malaise or backache, was defined as a case. For every case in a district, a corresponding control was traced and matched by sex using multistage cluster sampling. Other criteria for inclusion as a control included a negative c-ELISA test result and that the matched individual would present to hospital if falls sick. Results: Multivariable analysis showed that brucellosis was associated with assisted parturition during abortion in cattle, sheep or goat. It was shown that individuals living in close proximity to other households had a higher risk of brucellosis. People who were of Christian religion were found to have a higher risk of brucellosis compared to other religions. The study concludes that assisting an aborting animal, proximity to neighborhoods, and Christianity were associated with brucellosis infection. There was no association between human brucellosis and Human Immunodeficiency Virus (HIV) serostatus. Protecting humans against contact with fluids and tissues during assisted parturition of livestock may be an important means of reducing the risk of transferring brucellosis from livestock to humans. These can be achieved through health education to the communities where brucellosis is common.Item Risk Factors for Human Brucellosis in Northern Tanzania.(The American Society of Tropical Medicine and Hygiene., 2018) Cash-Goldwasser, S.; Maze, M. J.; Rubach, M. P.; Biggs, H. M.; Stoddard, R. A.; Sharples, K. J.; Halliday, J. E. B.; Cleaveland, S.; Shand, M. C.; Mmbaga, B. T.; Muiruri, C.; Saganda, W.; Lwezaula, B. F.; Kazwala, R. R.; Maro, V. P.; Crump, J. A.Little is known about the epidemiology of human brucellosis in sub-Saharan Africa. This hampers prevention and control efforts at the individual and population levels. To evaluate risk factors for brucellosis in northern Tanzania, we conducted a study of patients presenting with fever to two hospitals in Moshi, Tanzania. Serum taken at enrollment and at 4-6 week follow-up was tested by Brucella microagglutination test. Among participants with a clinically compatible illness, confirmed brucellosis cases were defined as having a ≥ 4-fold rise in agglutination titer between paired sera or a blood culture positive for Brucella spp., and probable brucellosis cases were defined as having a single reciprocal titer ≥ 160. Controls had reciprocal titers < 20 in paired sera. We collected demographic and clinical information and administered a risk factor questionnaire. Of 562 participants in the analysis, 50 (8.9%) had confirmed or probable brucellosis. Multivariable analysis showed that risk factors for brucellosis included assisting goat or sheep births (Odds ratio [OR] 5.9, 95% confidence interval [CI] 1.4, 24.6) and having contact with cattle (OR 1.2, 95% CI 1.0, 1.4). Consuming boiled or pasteurized dairy products was protective against brucellosis (OR 0.12, 95% CI 0.02, 0.93). No participants received a clinical diagnosis of brucellosis from their healthcare providers. The under-recognition of brucellosis by healthcare workers could be addressed with clinician education and better access to brucellosis diagnostic tests. Interventions focused on protecting livestock keepers, especially those who assist goat or sheep births, are needed.Item The role of livestock keeping in tuberculosis trends in Arusha, Tanzania(The International Journal of Tuberculosis and Lung Disease, 2003-01-15) Mfinanga, S. G.; Mørkve, O.; Kazwala, R. R.; Cleaveland, S.; Sharp, J. M.; Shirima, G.; Nilsen, R.OBJECTIVE: To assess risk factors that might influence TB control in the general population and in livestockkeepers. METHODS: Of 242 villages in four districts, 27 were selected randomly. In each village, a general and a livestock- keeping group were selected at random. The households were home-visited and 426 family members were interviewed. RESULTS: On average, three-quarters of households practised at least one risk activity for transmission of zoonotic tuberculosis, and respondents had poor knowledge about tuberculosis. In the livestock-keeping group, the risks of having a tuberculosis patient in the family were determined by poor ventilation (OR 2.6, 95%CI 1.1–6.5), confining livestock indoors with people (OR 2.3, 95%CI 1.1–5.0) and multiple determinants including poor ventilation (OR 13.5, 95%CI 2.5–71.7). Risk activities and the risks of having a tuberculosis patient in a family were significantly higher in the livestock-keeping group. CONCLUSIONS: The respondents had limited knowledge about tuberculosis, and the households had practices that posed potential risks for both human and bovine tuberculosis infection. Poor ventilation and confining livestock indoors were associated with tuberculosis spread in the households. These risks were observed more in the livestock-keeping group than in the general population group.Item Toward Elimination of Dog-Mediated Human Rabies: Experiences from Implementing a Large-scale Demonstration Project in Southern Tanzania(Original research article., 2017) Mpolya, E. A; Lembo, T.; Lushasi, K.; Mancy, R.; Mbunda, E. M.; Makungu, S.; Maziku, M.; Sikana, L.; Jaswant, G.; Townsend, S.; Meslin, F. X.; Abela, B.; Ngeleja, C.; Changalucha, J.; Mtema, Z.; Sambo, M.; Mchau, G.; Rysava, K.; Nanai, A.; Kazwala, R.; Cleaveland, S.; Hampson, K.A Rabies Elimination Demonstration Project was implemented in Tanzania from 2010 through to 2015, bringing together government ministries from the health and veterinary sectors, the World Health Organization, and national and international research institutions. Detailed data on mass dog vaccination campaigns, bite exposures, use of post-exposure prophylaxis (PEP), and human rabies deaths were collected throughout the project duration and project areas. Despite no previous experience in dog vaccination within the project areas, district veterinary officers were able to implement district-wide vaccination campaigns that, for most part, progressively increased the numbers of dogs vaccinated with each phase of the project. Bite exposures declined, particularly in the southernmost districts with the smallest dog populations, and health workers successfully transitioned from primarily intramuscular administration of PEP to intradermal administration, resulting in major cost savings. However, even with improved PEP provision, vaccine shortages still occurred in some districts. In laboratory diagnosis, there were several logistical challenges in sample handling and submission but compared to the situation before the project started, there was a moderate increase in the number of laboratory samples submitted and tested for rabies in the project areas with a decrease in the proportion of rabies-positive samples over time. The project had a major impact on public health policy and practice with the formation of a One Health Coordination Unit at the Prime Minister’s Office and development of the Tanzania National Rabies Control Strategy, which lays a roadmap for elimination of rabies in Tanzania by 2030 by following the Stepwise Approach towards Rabies Elimination (SARE). Overall, the project generated many important lessons relevant to rabies prevention and control in particular and disease surveillance in general. Lessons include the need for (1) a specific unit in the government for managing disease surveillance; (2) application of innovative data collection and management approaches such as the use of mobile phones; (3) close cooperation and effective communication among all key sectors and stakeholders; and (4) flexible and adaptive programs that can incorporate new information to improve their delivery, and overcome challenges of logistics and procurement.Item Tribal differences in perception of tuberculosis: A possible role in tuberculosis control in Arusha, Tanzania(International Journal of Tuberculosis and Lung Disease., 2003) Mfinanga, S. G.; Mørkve, O.; Kazwala, R. R.; Cleaveland, S.; Sharp, J. M.; Shirima, G.; Nilsen, R.SETTING: Arusha, Tanzania. OBJECTIVE: To determine tribal differences in knowledge and practices that might influence tuberculosis control. METHOD: Twenty-seven villages were selected randomly out of 242 villages in four districts. In each village, a general and a livestock keeping group were selected at random. The households were home-visited and 426 family members were interviewed. RESULTS: On average, 40% of respondents practiced habits that might expose them to both bovine and human tuberculosis. The Barabaig tribe had a significantly higher number of respondents (50%, X2(2) = 5.1, P = 0.024) who did not boil milk. Eating uncooked meat or meat products was practised by 17.9% of all respondents. The habit was practised more by Iraqw (21.1%, X2(2) = 6.9, P = 0.008) and Barabaig (31.6%, X2(2) = 5.6, P = 0.016) than other tribes. About 75% of the respondents had a poor knowledge of tuberculosis. CONCLUSION: All tribes had habits and beliefs that might expose them to both bovine and human tuberculosis. The Iraqw and Barabaig tribes practised such habits more than other tribes. Knowledge of tuberculosis was limited in all tribes.Item Tuberculosis in Tanzanian Wildlife(Journal of Wildlife Diseases, 2005) Cleaveland, S.; Mlengeya, T.; Kazwala, R. R.; Michel, A.; Kaare, M. T.; Jones, S. L.; Eblate, E.; Shirima, G. M.; Packer, C.Bovine tuberculosis, caused by Mycobacterium bovis, is a pathogen of growing concern in free-ranging wildlife in Africa, but little is known about the disease in Tanzanian wildlife. Here, we report the infection status of Mycobacterium bovis in a range of wildlife species sampled from protected areas in northern Tanzania. M. bovis was isolated from 11.1% (2/ 18) migratory wildebeest (Connochaetes taurinus) and 11.1% (1/9) topi (Damaliscus lunatus) sampled systematically in 2000 during a meat cropping program in the Serengeti ecosystem, and from one wildebeest and one lesser kudu (Tragelaphus imberbis) killed by sport hunters adjacent to Tarangire National Park. A tuberculosis antibody enzyme immunoassay (EIA) was used to screen serum samples collected from 184 Serengeti lions (Panthera leo) and 19 lions from Ngorongoro Crater sampled between 1985 and 2000. Samples from 212 ungulates collected throughout the protected area network between 1998 and 2001 also were tested by EIA. Serological assays detected antibodies to M. bovis in 4% of Serengeti lions; one positive lion was sampled in 1984. Antibodies were detected in one of 17 (6%) buffalo (Syncerus caffer) in Tarangire and one of 41 (2%) wildebeest in the Serengeti. This study confirms for the first time the presence of bovine tuberculosis in wildlife of northern Tanzania, but further investigation is required to assess the impact on wildlife populations and the role of different wildlife species in maintenance and transmission.