Animal sentinel surveillance: evaluating domestic dogs as sentinels for zoonotic pathogen surveillance

The capacity of zoonotic pathogens to infect multiple hosts creates surveillance challenges but also provides opportunities to gather data from animal species that can be used to understand risks to human health. This thesis presents a conceptual and practical assessment of the utility of domestic dog serosurveillance for the detection and surveillance of two pathogens, influenza A and Leptospira spp. The first chapter gives a theoretical framework that can be used to explore the attributes of animal sentinels and assess their utility in different contexts. In subsequent chapters, this framework is applied in a practical assessment of the utility of a domestic dog serosurveillance approach for the detection and surveillance influenza A and Leptospira spp. at two sites in Africa. Two cross-sectional surveys of the avian and mammal populations at a site in Northern Cameroon were conducted in early 2006 to determine if H5N1 influenza A viruses had circulated in this area and in which species that presence could be detected. Serological and molecular evidence of extensive H5 virus circulation in the domestic duck population was identified. 47% of domestic ducks at the Maga site were cELISA positive for anti-influenza A antibodies and 20% were HI test positive against an H5N1 antigen. There was also evidence of exposure to H5 subtype viruses in the local dog and pig populations. At the Kibera site in Nairobi, a cohort study was established to carry out surveillance of influenza A and Leptospira spp. in the domestic dog population and cross-sectional surveys of the domestic poultry and rodent populations were completed. There was no indication of influenza A circulation in any of the animal species surveyed, indicating low risk of zoonotic influenza A infection in the human population of Kibera. In contrast, there was extensive molecular and serological evidence of the presence of Leptospira spp. in both the rodent and dog populations. 18% of 236 trapped rodents were PCR positive for kidney carriage of pathogenic leptospires and the estimated seroprevalence of anti- Leptospira antibodies in the dog population ranged from 5-36% during the course of the study, indicating high potential risk of leptospirosis infection in the human population. The results indicate that dog serosurveillance can be used as useful tool for the determination of broad-scale patterns of pathogen presence and relative levels of population exposure. However, there are limitations of the data that can be gathered from animal sentinels and the complexities introduced particularly by incomplete understanding of diagnostic test performance must be recognized. Animal sentinel surveillance may be of most use for addressing fundamental questions of what pathogens are present where. In the developing world particularly where disease burden data are still lacking, dog sentinel serosurveillance can provide essential baseline data that can be used to target future research and resource allocation

Herd-level risk factors associated with the presence of Phage type 21/28 E. coli O157 on Scottish cattle farms

<p>Background: E. coli O157 is a bacterial pathogen that is shed by cattle and can cause severe disease in humans. Phage type (PT) 21/28 is a subtype of E. coli O157 that is found across Scotland and is associated with particularly severe human morbidity.</p> <p>Methods: A cross-sectional survey of Scottish cattle farms was conducted in the period Feb 2002-Feb 2004 to determine the prevalence of E. coli O157 in cattle herds. Data from 88 farms on which E. coli O157 was present were analysed using generalised linear mixed models to identify risk factors for the presence of PT 21/28 specifically.</p> <p>Results: The analysis identified private water supply, and northerly farm location as risk factors for PT 21/28 presence. There was a significant association between the presence of PT 21/28 and an increased number of E. coli O157 positive pat samples from a farm, and PT 21/28 was significantly associated with larger E. coli O157 counts than non-PT 21/28 E. coli O157.</p> <p>Conclusion: PT 21/28 has significant risk factors that distinguish it from other phage types of E. coli O157. This finding has implications for the control of E. coli O157 as a whole and suggests that control could be tailored to target the locally dominant PT.</p&gt

Mixed methods survey of zoonotic disease awareness and practice among animal and human healthcare providers in Moshi, Tanzania

This work was supported by US National Institutes of Health-National (NIH) Science Foundation Ecology and Evolution of Infectious Disease program (R01 TW009237) and the UK Biotechnology and Biological Sciences Research Council (BBSRC) (BB/J010367). Additional support was provided by BBSRC grants BB/L018845 (RRK, JAC and JEBH) and BB/L018926 (SC, RRK, JPS and JAC). JAC is supported by NIH grant R01 TW009237 and Bill & Melinda Gates Foundation grant OPP1125993. JPS had additional support from an ESRC fellowship, RES-070-27-0039. HLZ received support from the Doris Duke Charitable Foundation through a grant supporting the Doris Duke International Clinical Research Fellows Program at Duke University.Background:  Zoonoses are common causes of human and livestock illness in Tanzania. Previous studies have shown that brucellosis, leptospirosis, and Q fever account for a large proportion of human febrile illness in northern Tanzania, yet they are infrequently diagnosed. We conducted this study to assess awareness and knowledge regarding selected zoonoses among healthcare providers in Moshi, Tanzania; to determine what diagnostic and treatment protocols are utilized; and obtain insights into contextual factors contributing to the apparent under-diagnosis of zoonoses. Methodology/Results:  We conducted a questionnaire about zoonoses knowledge, case reporting, and testing with 52 human health practitioners and 10 livestock health providers. Immediately following questionnaire administration, we conducted semi-structured interviews with 60 of these respondents, using the findings of a previous fever etiology study to prompt conversation. Sixty respondents (97%) had heard of brucellosis, 26 (42%) leptospirosis, and 20 (32%) Q fever. Animal sector respondents reported seeing cases of animal brucellosis (4), rabies (4), and anthrax (3) in the previous 12 months. Human sector respondents reported cases of human brucellosis (15, 29%), rabies (9, 18%) and anthrax (6, 12%). None reported leptospirosis or Q fever cases. Nineteen respondents were aware of a local diagnostic test for human brucellosis. Reports of tests for human leptospirosis or Q fever, or for any of the study pathogens in animals, were rare. Many respondents expressed awareness of malaria over-diagnosis and zoonoses under-diagnosis, and many identified low knowledge and testing capacity as reasons for zoonoses under-diagnosis. Conclusions: This study revealed differences in knowledge of different zoonoses and low case report frequencies of brucellosis, leptospirosis, and Q fever. There was a lack of known diagnostic services for leptospirosis and Q fever. These findings emphasize a need for improved diagnostic capacity alongside healthcare provider education and improved clinical guidelines for syndrome-based disease management to provoke diagnostic consideration of locally relevant zoonoses in the absence of laboratory confirmation.Publisher PDFPeer reviewe

One Health contributions towards more effective and equitable approaches to health in low- and middle-income countries

This research was supported by the UK Biotechnology and Biological Sciences Research Council (BB/J010367/1) and the UK Zoonoses and Emerging Livestock Systems Initiative (BB/L017679/1, BB/L018926/1 and BB/L018845/1) (S.C., J.E.B.H., J.S., J.B., A.D., J.A.C., W.A.d.G., R.R.K., T.K., D.T.H., B.T.M., E.S.S., L.W.). The Wellcome Trust provided supported for K.H. and A.L. (095787/Z/11/Z) and K.J.A. (096400/Z/11/Z). The US National Institutes of Health provided support for J.A.C. (R01AI121378) and M.P.R. (R01AI121378, K23AI116869).Emerging zoonoses with pandemic potential are a stated priority for the global health security agenda, but endemic zoonoses also have a major societal impact in low-resource settings. Although many endemic zoonoses can be treated, timely diagnosis and appropriate clinical management of human cases is often challenging. Preventive ‘One Health’ interventions, e.g. interventions in animal populations that generate human health benefits, may provide a useful approach to overcoming some of these challenges. Effective strategies, such as animal vaccination, already exist for the prevention, control and elimination of many endemic zoonoses, including rabies, and several livestock zoonoses (e.g. brucellosis, leptospirosis, Q fever) that are important causes of human febrile illness and livestock productivity losses in low- and middle-income countries. We make the case that, for these diseases, One Health interventions have the potential to be more effective and generate more equitable benefits for human health and livelihoods, particularly in rural areas, than approaches that rely exclusively on treatment of human cases. We hypothesize that applying One Health interventions to tackle these health challenges will help to build trust, community engagement and cross-sectoral collaboration, which will in turn strengthen the capacity of fragile health systems to respond to the threat of emerging zoonoses and other future health challenges. One Health interventions thus have the potential to align the ongoing needs of disadvantaged communities with the concerns of the broader global community, providing a pragmatic and equitable approach to meeting the global goals for sustainable development and supporting the global health security agenda.Publisher PDFPeer reviewe

Chacma baboon mating markets: competitor suppression mediates the potential for intersexual exchange

Contrary to the expectations of biological market theory, in species where sexual coercion is effective males often exchange resources or services with females for the opportunity to mate. This suggests that an ability to control mating partners does not preclude the need for their cooperation. We argue that this is because, in many systems, female resistance to coercion can precipitate intermale competition and, as such, a male's mating strategy may often be better served by securing female compliance through affiliative rather than agonistic means. Based on this reasoning, we predicted that the need for males to exchange resources/services for mating access with females will be absent only when intermale power differentials are such that dominant individuals can secure uncontested access to receptive females. Accordingly, data from our long-term study site revealed no support for a biological markets model of intersexual mating exchange in chacma baboons, where the mating monopolies of alpha males are near absolute. Specifically, we found that males groomed females substantially less than they were groomed by them, their propensity to groom was poorly described by measures of female fertility, male rank, and the operational sex ratio, and their mating success was not associated with their grooming effort. We further predicted that an additional consequence of the degree of competitor suppression seen in chacma would be a reversal in the direction of intersexual trade of services for mating. We found that female grooming was positively associated with the probability that they would successfully initiate a copulation. Our study strongly suggests that it is variance in competitor suppression, not partner control, that mediates the potential for and direction of intersexual cooperative exchange. Copyright 2010, Oxford University Press.

Coxiella burnetii in humans, domestic ruminants, and ticks in rural Western Kenya

We conducted serological surveys for Coxiella burnetii in archived sera from patients that visited a rural clinic in western Kenya from 2007 to 2008 and in cattle, sheep, and goats from the same area in 2009. We also conducted serological and polymerase chain reaction-based surveillance for the pathogen in 2009–2010, in human patients with acute lower respiratory illness, in ruminants following parturition, and in ticks collected from ruminants and domestic dogs. Antibodies against C. burnetii were detected in 30.9% (N = 246) of archived patient sera and in 28.3% (N = 463) of cattle, 32.0% (N = 378) of goats, and 18.2% (N = 159) of sheep surveyed. Four of 135 (3%) patients with acute lower respiratory illness showed seroconversion to C. burnetii. The pathogen was detected by polymerase chain reaction in specimens collected from three of six small ruminants that gave birth within the preceding 24 hours, and in five of 10 pools (50%) of Haemaphysalis leachi ticks collected from domestic dogs