Evaluation Of Movements And Habitat Use Of Suburban Striped Skunks (Mephitis Mephitis) In The Northern Great Plains To Inform Rabies Management

Few studies have investigated the ecology of urban striped skunks (Mephitis mephitis) despite their role as a primary rabies vector species paired with an ability to thrive in these landscapes. Our aim was to obtain baseline ecological information with an emphasis on spatial ecology of urban striped skunks in the Northern Great Plains region that is missing in the literature. This information, such as home range, nightly movements, habitat selection, and denning behavior is important for informing rabies management decisions such as the placement of oral rabies vaccine (ORV) baits. We used radio telemetry equipment to track 22 (4M, 18 F) skunks from September 2016âNovember 2016 and March 2017âNovember 2017 and monitored denning sites with trail cameras October 2016âJuly 2017. Size of home ranges estimated using kernel density estimation and least squares cross validation determined males (x Ì = 4.36 km2, SE ± 0.79) had larger home ranges than females (x Ì = 1.79 km2, SE ± 0.24). Female skunk home ranges differed by season with the largest home ranges found in summer 2017. However, rate of nightly movements (m/hr) among female skunks did not differ within seasons (x Ì = 184.79 m/hr, SE ± 0.53). Moreover, we found no evidence that use-availability was associated with habitat type among female skunks. The strongest predictor of habitat use was distance to water sources with female skunks more likely to be found closer to this habitat type; however, we found no association of use with road factors and geographic location within the city. We observed communal denning in 3 winter den sites, which could amplify rabies transmission during these periods of inactivity. Targeting ORV efforts in areas near water and den sites may be warranted, but considering differences in urban skunk habitat selection studies, we caution that ORV baiting programs may not be one-size-fits-all, and a framework for effective bait placement would be most successful should similar studies be conducted beforehand

One Health and Neglected Tropical Diseases

“One Health” is defined as an approach to achieve better health outcomes for humans, animals, and the environment through collaborative and interdisciplinary efforts. The One Health framework is increasingly being applied to the management, control, and even elimination of neglected tropical diseases (NTDs), a set of infectious diseases that, collectively, affect more than one billion people across almost 150 countries. NTDs are some of the most common infections in the world; they cause substantial morbidity and mortality, particularly in regions with little access to medical care and other resources. Although there is increasing recognition of the major public health threat presented by NTDs, the ecological complexities of their transmission continue to pose challenges for their control and elimination. Some NTDs are zoonotic, meaning that they can be transmitted between humans and animals and, as such, present obstacles for public health and veterinary services in addition to concerns for wildlife conservation. Vector-borne NTDs necessitate measures that integrate consideration of the environment into public health strategies in order to sustainably reduce disease transmission. This book presents a collection of papers that explore various aspects of how the One Health concept is being applied to NTD control around the world, from genomics and diagnostic tools to improved surveillance and disease management. Encompassing research from Central America, the Caribbean, Asia, and sub-Saharan Africa, the collection emphasizes the diversity of NTDs as well as the critical importance of multisectoral collaboration for their control and elimination

One Health for Dog-mediated Rabies Elimination in Asia. A Collection of Local Experiences

Although an effective human rabies vaccine has existed since 1885, rabies continues to kill an estimated 59,000 people every year. Sixty per cent of these human deaths occur in Asia. The number of animals, especially dogs, who die of rabies is uncalculated. To work towards the global target of eliminating dog-mediated human rabies deaths, the rabies community is applying the One Health approach by jointly focusing on humans and dogs. Written by a multidisciplinary group of scholars and rabies control programme specialists, this book is a collection of experiences and observations on the challenges and successes along the path to rabies control and prevention in Asia. The book: grounds chapters in solid scientific theory, but retains a direct, practice-focused and inspirational approach;provides numerous examples of lessons learned and experience-based knowledge gained across countries at different levels of rabies elimination;brings together and highlights the practices of a strong, international rabies network that works according to the One Health concept. Covering perspectives from almost a dozen Asian countries and a wide range of sectors and disciplines, such as healthcare facilities, veterinary services, laboratories, public health institutes, wildlife research centres and academia, this book is an invaluable resource for rabies practitioners and scholars, but also those working in the wider fields of disease control and cross-sectoral One Health

Rabies control in N'Djamena, Chad

Rabies is a viral disease that induces invariably fatal encephalitis. Most affected by the disease are resource poor countries. Worldwide burden estimates reveal that the disease claims about one human victim every ten minutes. Transmission of the virus to humans occurs in over 95% through a bite of an infected dog. The only method for sustainable control of canine rabies and elimination at the source is dog vaccination. Since the year 2000 Swiss TPH works in close partnership with the Institut de Recherche en Élevage pour le Développement (IRED) and the Centre de Support en Santé Internationale (CSSI) on the control of rabies in N’Djaména, the capital city of Chad. The project phase from 2012-2015 has led to my doctoral thesis, which spans over many aspects of rabies control. Two mass vaccination campaigns have been conducted in 2012 and 2013 that covered the whole town and reached consecutively over 70% of the canine population. The intervention led to a drastic drop of dog rabies incidence. Data on animal rabies incidence, bite exposure incidence and Post-Exposure Prophylaxis (PEP) demand were used to validate a dog to human transmission model and to update the cost-effectiveness analysis of dog vaccination. The thesis also includes the validation of a rapid, simple rabies diagnostic test that has the potential to enhance surveillance in resource poor settings. On the national level economic aspects of a countrywide control program, a dog demographic survey and a Knowledge Attitude and Practices (KAP) study among the Chadian population are presented. Finally, social determinants of accessibility and effectiveness of rabies vaccination campaigns are discussed, by comparing the results from N’Djamena with a similar study in Bamako, Mali

Modelling canine rabies elimination in India through mass dog vaccination

The ‘Zero by 30’ campaign aims to globally eliminate dog-mediated human rabies deaths by 2030. Theoretical and empirical studies have shown that annual mass rabies vaccination (MRV) campaigns that vaccinate at least 70% of the dog population in an area can effectively control canine rabies outbreaks and eventually eliminate it. Achieving such coverages in free-ranging dog (FRD) populations, the main source of human infections in rabies-endemic regions, can be a major challenge where most FRDs are unowned and so not easily accessible for vaccination. Despite bearing the largest burden of human rabies deaths globally, few studies have explored the population characteristics of FRDs in India in the context of rabies elimination, particularly accessibility for vaccination. Similarly, there are limited studies of dog ownership practices (DOP) relevant to rabies control in India. We conducted a longitudinal field study over 16 months in a cohort of unowned dogs (UDs), semi-owned dogs (SODs) and ODs at an urban (human population of 240991 individuals) and a semi-urban (25861 individuals) site each in Kerala, south India. The study gathered data on dog population characteristics, DOP and pre- and post-vaccination rabies virus neutralizing antibody (RVNA) dynamics. In round 1 (R1) pre-vaccination blood samples were collected from all dogs, after which they were vaccinated against rabies, collared and microchipped where necessary and released. Data on demographic characteristics (sex, age, body condition etc.) and DOP were also collected. As many dogs as possible from this cohort were recaptured at approximately ~30 days (R2), ~150 – 180 days (R3) and ~365 days (R4) after first capture to collect post-vaccination blood samples. All serum samples were tested to assess post-vaccination RVNA titre dynamics and rates of decline. These data were used to parameterise an age-structured deterministic compartmental Susceptible-Exposed-Infectious-Vaccinated (SEIV) model incorporating assumptions about accessibility for vaccination. The model was used to assess the impacts of varying various demographic, immunological and MRV campaign parameters on prospects of rabies elimination within 20 years of campaign implementation. In R1, 577 dogs across all ownership categories were captured. Only 12% of FRDs were owned, with about 60% of ODs in R1 being free-ranging. Only 29% of ODs were vaccinated against rabies. Approximately 26% (95% CIs: 22 – 31%) of all dogs sampled in R1 had RVNA titres ≥ 0.23 IU/ml. Mixed-effects logistic regression models found higher recapture probabilities for sterilised dogs and lower probabilities for UDs, dogs from the semi-urban site and those with pre-vaccination RVNA titres ≤ 0.5 IU/ml or no detectable titres. Over 80% of dogs recaptured in R2 had titres > 0.5 IU/ml, irrespective of age or vaccination history. Mixed-effects linear regression models identified significant associations between post-vaccination RVNA titres and age at vaccination, sterilisation status and RVNA titre levels in R1. Titres were estimated to drop below 0.5 IU/ml approximately 200 days (95% CI: 167 – 256 days) after achieving post-vaccination peak levels. However, titres declined at a faster rate for ODs and completely/partially confined dogs compared to dogs without owners and completely FRDs. We also found evidence suggesting the occurrence of non-lethal rabies infections in FRDs. The SEIV model indicated that as accessibility for vaccination increased, rabies elimination was possible in a wider range of scenarios within shorter timeframes, generally within 10 years of implementation of vaccination campaigns, and required lower vaccination coverages. Where ≤ 20% of dogs were accessible, campaigns needed to consistently vaccinate > 95% of dogs for > 20 years to eliminate rabies. Rabies elimination was possible in most scenarios, typically with annual campaigns, even with < 70% effective vaccination coverages in the total dog population. The model also highlighted the complex interplay of demographic factors and disease transmission, with high birth rates resulting in higher rabies cases, irrespective of juvenile mortality or adult lifespan. Mass rabies vaccination continues to be the most effective rabies control method; however, the implementation and frequency of MRV campaigns must account for varying accessibility of FRD populations and consider variations in demography and immunological dynamics. Rabies control in India will require a multi-pronged approach incorporating more responsible dog ownership, access to veterinary care, effective MRV and dog population and waste management, while ensuring the use of properly stored, high-quality vaccines and where necessary, the use of alternative vaccination methods such as oral vaccines to access as many dogs as possible.Open Acces

Studies on the epidemiology and control of rabies in Bhutan

Rabies, a fatal and neglected zoonotic disease, is reported mainly from the southern parts of Bhutan bordering India, but sporadic occurrences have been reported in other, previously free areas. Domestic dogs play a principal role in the transmission of rabies and no wildlife rabies cases have been reported so far in Bhutan. Although rabies has been endemic and causes substantial financial losses, no detailed studies have been conducted to understand the epidemiology of rabies in Bhutan. The overall objective of this research was to better understand the epidemiology of animal and human rabies and estimate the cost of various rabies intervention measures in humans and animals. This was the first epidemiologic research on rabies ever conducted in Bhutan. Rabies surveillance data (1996 to 2009) and field surveys were used for this epidemiologic research. The spatial and temporal distribution of animal rabies cases was examined by using a Geographic Information System and time series analysis approaches. The study showed that 59 of the 205 sub-districts in Bhutan reported animal rabies from 1996 to 2009 with increased incidences in the four districts in southern parts of Bhutan. Significant (P<0.05) clusters of cases were observed in south central and south west Bhutan. More cases were reported in cattle (n=447) and domestic dogs (n=317) and a significant cross correlation between the number of reported cases in dogs and other domestic animals was demonstrated, wherein the report of cases in dogs predicted cases in other domestic animals. Rabies cases were reported throughout the year with more reports during spring and summer months, likely to be associated with the breeding season of dogs. The annual patterns of cases were relatively stable until 2005, but increased in 2006 and 2008. This increased incidence was associated with re-emergence of rabies in eastern and south west Bhutan between 2005 and 2008, areas that had been previously free from rabies. This major rabies outbreak in eastern Bhutan resulted in one human and 256 domestic animal deaths while the outbreak in south west Bhutan resulted in 97 animal deaths; both outbreaks caused serious financial losses to society. During these outbreaks, large numbers of people (~2000) were directly or indirectly exposed to either suspected rabid animals or animal products derived from rabid animals and were given post-exposure prophylaxis. The outbreak in eastern Bhutan was believed to have been due to an incursion from across the border while local spread from the endemic areas or an incursion was hypothesized in the south-west Bhutan outbreak. The high densities and movements of stray dogs with inadequate control measures were responsible for the rapid spread and persistence of the infection for about two years (from May 2005 to November 2007) in eastern Bhutan. In contrast, the outbreak in south west Bhutan during 2008 was controlled within six months by culling of stray dogs, mass dog vaccination, and impounding of dogs. Anthropogenic factors − including human population characteristics and its movement, road network accessibility, and high dog density − played a major role in the spread of disease during both of these outbreaks. The assessment of risk factors for the occurrence of rabies at the sub-district level identified the socio-demographic and anthropogenic factors significantly associated with reporting of rabies in domestic animals in Bhutan. Sharing a common border with India was found to be the most important individual predictor of the overall distribution of rabies occurrence in Bhutan (odds ratio 10.43; 95% CI: 4.42–24.64; P<0.001). Of the 59 sub-districts that reported rabies in Bhutan, 43 (73%) shared a border with India. The trans-border movement or translocation of stray dogs and an inadequate control program may be responsible for the maintenance of rabies endemicity and transmission among the stray dog population in these border areas. Molecular and phylogenetic analyses further demonstrated that Bhutanese rabies virus isolates were found to be closely related to Indian rabies virus strain and belong to Arctic-like-1 viruses which are widely circulating in the Indian sub-continent. This study suggests that the rabies viruses spreading in southern parts of Bhutan have originated from a common ancestor. However, more sampling is needed from Bhutan-India border areas to understand the transmission dynamic of rabies virus in the region. In humans, rabies cases were found to be sporadic, mainly reported in the canine rabies endemic areas of southern Bhutan. A total of 15 human rabies deaths was reported between January 2006 and July 2011 (with 5 deaths reported in 2011 alone), equivalent to a cumulative incidence of 2.14 per 100000 population (annual incidence of 0.28 per 100000 people). Although the number of human rabies deaths was sporadic, there were increased number of dog bite incidents and post-exposure prophylaxis (PEP) administration to the patients. In order to understand the use and distribution of rabies PEP in humans, PEP data for the period from 2005 to 2008 were retrieved from the hospital medical database and analysed. The study showed that PEP was provided to the patients free of charge by the medical hospitals in Bhutan, and followed the 5-dose Essen intramuscular regimen. A significant (P<0.001) difference in gender and age groups receiving PEP was observed: males received more PEP than females across all age groups. Children − particularly 5–9 years of age − received more PEP than other age groups, indicating children and males are more at risk of rabies exposure in Bhutan. PEP was provided throughout the year with a higher number of doses administered during the winter and spring months, and was given to both animal bite and non-bite exposures. The study also identified a lack of patient compliance to complete the course of PEP: some 40% (n = 3360) of the patients received an incomplete course of vaccine (less than the required course of 5-doses). However, the results suggest that patients with animal bite injury were less likely to receive an incomplete vaccine course than non-bite recipients. Secondly, patients presented to hospitals in rabies endemic or outbreak areas were less likely to receive an incomplete course than in rabies free interior Bhutan, thus reducing the chances of vaccination failures. The study also showed that the PEP was provided to patients that have low or no risk of rabies exposure. Therefore, a thorough assessment of each individual case based on the WHO guidelines would reduce unnecessary use of PEP, and therefore costs in Bhutan. The main reason for providing PEP was found to be due to dog bites. To better understand the dog bites incidents in humans, a hospital-based survey was conducted at the three hospitals in Western and Southern Bhutan (Thimphu, Phuentsholing and Gelephu) for a period of nine months. The study revealed that dog bites in human are common in the survey areas and showed significant (P<0.001) gender and age differences in bite incidents. Males were more at risk of dog bites than females, and the children aged 5–9 years were bitten more than other age groups, which substantiate our earlier findings of more use of PEP in males and children. The majority of victims were bitten by stray dogs, and the most common anatomical bite sites were on the legs. Using data on the anatomical location of dog bites in humans and a probability of dying from rabies, a decision tree model was constructed to estimate human deaths from rabies in two rabies endemic areas of southern Bhutan. Based on the official reported cases of rabies in two hospital areas (Gelephu and Phuentsholing) in southern Bhutan, the average number of human rabies death was 1.5 (95% CI: 0.75–3.00) per year, equivalent to an annual incidence of 3.14 (95% CI: 1.57–6.29) per 100,000 population. The decision tree model predicted 2.23 (95% CI: 1.20−3.59) human deaths from rabies per year, equivalent to an annual incidence of 4.67 (95% CI: 2.53–7.53) deaths per 100,000 populations. This indicated that no major underreporting of human rabies deaths has occurred, unlike in other rabies endemic countries, although some underreporting of dog bites is possible. In the absence of post-exposure prophylaxis, the model predicted 19.24 (95% CI: 13.69–25.14) deaths per year, equivalent to an annual incidence of 40.31 (95% CI: 28.70–52.68) per 100,000 population, suggesting post-exposure prophylaxis is important to prevent human rabies deaths. Since both dog bite incidents and the use of PEP were high in Bhutan, a cross-sectional study was conducted at Gelephu (south central Bhutan), an area endemic for rabies, to understand people’s level of knowledge and awareness about rabies. The study showed that a majority of the interviewed respondents had heard of rabies, and had a positive attitude towards the prevention and control of rabies. About 84 to 92% of the respondents also mentioned that they would report to the hospital for treatment if bitten by dogs and other animals, indicating good health seeking behaviours of the people. The respondents also had a positive attitude towards prevention and control of rabies in dogs by vaccination. However, these findings also indicated the existence of some knowledge gaps (knowledge about rabies and its transmission and importance of wound washing) which could be filled by creating awareness education programmes on: the danger of rabies and mode of transmission to humans and importance washing animal bite wound and visiting a hospital for post-exposure prophylaxis. Since rabies causes substantial financial losses to society, understanding the cost-benefit or cost-effectiveness of the intervention programme is important. Quantification of the financial cost of rabies intervention in Bhutan suggested that the average direct medical cost of human PEP (using rabies vaccine only) was approximately Bhutanese Ngultrum (Nu) 1615 (US$35.65) per 5-dose Essen regimen per patient. The cost would increase to Nu. 2497 (US$ 55.13) and Nu. 19633 (US$433.41) per patient, if one dose of either equine rabies immunoglobulin (ERIG) or human rabies immunoglobulin (HRIG) was administered, respectively. The societal cost (public plus private cost) per patient was estimated to be Nu. 2019 (US$ 45), Nu. 2901 (US$64), and Nu. 20037 (US$ 442) using vaccine alone, vaccine with ERIG and vaccine with HRIG, respectively. The average cost per dog vaccination was estimated to be Nu. 75 (US$1.66) and the cost per dog sterilization was estimated to be Nu. 288 (US$ 6.52). The total direct medical cost due to rabies (including surveillance and livestock loss cost, PEP in human and dog vaccination and sterilization) between 2001 and 2008 was estimated to be Nu. 48.54 million (US$ 1.07 million). The analysis also showed that mass dog vaccination would be more cost-effective than intensified post-exposure prophylaxis in human alone. The above findings suggest that an area bordering India in the south were at higher risk of reporting rabies than the interior of Bhutan. More resources for rabies control programs and surveillance should be targeted and focussed in the highly endemic ‘hot spot’ areas of southern Bhutan. Mass vaccination of dogs in the border areas in the south would create an immune buffer (cordon sanitaire) and prevent incursion of rabies into interior Bhutan. A One-Health approach for rabies control in Bhutan should be implemented towards elimination of rabies through creation of effective partnership focussing on coordinating research, operational activities and pooling of resources between public health and veterinary services. Elimination of rabies through mass dog vaccination would reduce the recurrent cost of intensified PEP in humans and will produce economic savings in the long run by preventing human and livestock deaths and by discontinuing the intensified use of PEP in humans and rabies control programmes. Public awareness education is necessary and should include: the risk of rabies exposure; importance of preventing dog bites and wound washing and visiting health centres following dog bites and exposure to suspected rabid animals. Epidemiological surveillance of rabies should be improved by the laboratory confirmation of all suspected cases, including human, and the data so generated should be shared between the public health and veterinary sectors and also relevant international organizations. International collaboration is necessary for technical and financial support for sustaining rabies control in Bhutan

Solid waste management and social inclusion of waste pickers: opportunities and challenges

This repository item contains a working paper from the Boston University Global Economic Governance Initiative. The Global Economic Governance Initiative (GEGI) is a research program of the Center for Finance, Law & Policy, the Frederick S. Pardee Center for the Study of the Longer-Range Future, and the Frederick S. Pardee School of Global Studies. It was founded in 2008 to advance policy-relevant knowledge about governance for financial stability, human development, and the environment.In this paper we explore the opportunities and challenges inherent in the model of cooperation between municipal solid waste systems (MWSs) and waste picker cooperatives (WPCs). There is growing enthusiasm about waste picker inclusion, often as part of ‘integrated solid waste management.’ The World Bank and the InterAmerican Development Bank, for example, have both funded projects to support waste picker integration into formal sector recycling. Advocacy organizations such as WIEGO have called for an intensification of such efforts through access to credit and technology, as well as through partnerships to collect recyclables in underserved communities. These measures have given many waste pickers higher standards of living, economic security and a sense of inclusion in society. [TRUNCATED

Studies on the epidemiology and control of rabies in Bhutan

Rabies, a fatal and neglected zoonotic disease, is reported mainly from the southern parts of Bhutan bordering India, but sporadic occurrences have been reported in other, previously free areas. Domestic dogs play a principal role in the transmission of rabies and no wildlife rabies cases have been reported so far in Bhutan. Although rabies has been endemic and causes substantial financial losses, no detailed studies have been conducted to understand the epidemiology of rabies in Bhutan. The overall objective of this research was to better understand the epidemiology of animal and human rabies and estimate the cost of various rabies intervention measures in humans and animals. This was the first epidemiologic research on rabies ever conducted in Bhutan. Rabies surveillance data (1996 to 2009) and field surveys were used for this epidemiologic research. The spatial and temporal distribution of animal rabies cases was examined by using a Geographic Information System and time series analysis approaches. The study showed that 59 of the 205 sub-districts in Bhutan reported animal rabies from 1996 to 2009 with increased incidences in the four districts in southern parts of Bhutan. Significant (P<0.05) clusters of cases were observed in south central and south west Bhutan. More cases were reported in cattle (n=447) and domestic dogs (n=317) and a significant cross correlation between the number of reported cases in dogs and other domestic animals was demonstrated, wherein the report of cases in dogs predicted cases in other domestic animals. Rabies cases were reported throughout the year with more reports during spring and summer months, likely to be associated with the breeding season of dogs. The annual patterns of cases were relatively stable until 2005, but increased in 2006 and 2008. This increased incidence was associated with re-emergence of rabies in eastern and south west Bhutan between 2005 and 2008, areas that had been previously free from rabies. This major rabies outbreak in eastern Bhutan resulted in one human and 256 domestic animal deaths while the outbreak in south west Bhutan resulted in 97 animal deaths; both outbreaks caused serious financial losses to society. During these outbreaks, large numbers of people (~2000) were directly or indirectly exposed to either suspected rabid animals or animal products derived from rabid animals and were given post-exposure prophylaxis. The outbreak in eastern Bhutan was believed to have been due to an incursion from across the border while local spread from the endemic areas or an incursion was hypothesized in the south-west Bhutan outbreak. The high densities and movements of stray dogs with inadequate control measures were responsible for the rapid spread and persistence of the infection for about two years (from May 2005 to November 2007) in eastern Bhutan. In contrast, the outbreak in south west Bhutan during 2008 was controlled within six months by culling of stray dogs, mass dog vaccination, and impounding of dogs. Anthropogenic factors − including human population characteristics and its movement, road network accessibility, and high dog density − played a major role in the spread of disease during both of these outbreaks. The assessment of risk factors for the occurrence of rabies at the sub-district level identified the socio-demographic and anthropogenic factors significantly associated with reporting of rabies in domestic animals in Bhutan. Sharing a common border with India was found to be the most important individual predictor of the overall distribution of rabies occurrence in Bhutan (odds ratio 10.43; 95% CI: 4.42–24.64; P<0.001). Of the 59 sub-districts that reported rabies in Bhutan, 43 (73%) shared a border with India. The trans-border movement or translocation of stray dogs and an inadequate control program may be responsible for the maintenance of rabies endemicity and transmission among the stray dog population in these border areas. Molecular and phylogenetic analyses further demonstrated that Bhutanese rabies virus isolates were found to be closely related to Indian rabies virus strain and belong to Arctic-like-1 viruses which are widely circulating in the Indian sub-continent. This study suggests that the rabies viruses spreading in southern parts of Bhutan have originated from a common ancestor. However, more sampling is needed from Bhutan-India border areas to understand the transmission dynamic of rabies virus in the region. In humans, rabies cases were found to be sporadic, mainly reported in the canine rabies endemic areas of southern Bhutan. A total of 15 human rabies deaths was reported between January 2006 and July 2011 (with 5 deaths reported in 2011 alone), equivalent to a cumulative incidence of 2.14 per 100000 population (annual incidence of 0.28 per 100000 people). Although the number of human rabies deaths was sporadic, there were increased number of dog bite incidents and post-exposure prophylaxis (PEP) administration to the patients. In order to understand the use and distribution of rabies PEP in humans, PEP data for the period from 2005 to 2008 were retrieved from the hospital medical database and analysed. The study showed that PEP was provided to the patients free of charge by the medical hospitals in Bhutan, and followed the 5-dose Essen intramuscular regimen. A significant (P<0.001) difference in gender and age groups receiving PEP was observed: males received more PEP than females across all age groups. Children − particularly 5–9 years of age − received more PEP than other age groups, indicating children and males are more at risk of rabies exposure in Bhutan. PEP was provided throughout the year with a higher number of doses administered during the winter and spring months, and was given to both animal bite and non-bite exposures. The study also identified a lack of patient compliance to complete the course of PEP: some 40% (n = 3360) of the patients received an incomplete course of vaccine (less than the required course of 5-doses). However, the results suggest that patients with animal bite injury were less likely to receive an incomplete vaccine course than non-bite recipients. Secondly, patients presented to hospitals in rabies endemic or outbreak areas were less likely to receive an incomplete course than in rabies free interior Bhutan, thus reducing the chances of vaccination failures. The study also showed that the PEP was provided to patients that have low or no risk of rabies exposure. Therefore, a thorough assessment of each individual case based on the WHO guidelines would reduce unnecessary use of PEP, and therefore costs in Bhutan. The main reason for providing PEP was found to be due to dog bites. To better understand the dog bites incidents in humans, a hospital-based survey was conducted at the three hospitals in Western and Southern Bhutan (Thimphu, Phuentsholing and Gelephu) for a period of nine months. The study revealed that dog bites in human are common in the survey areas and showed significant (P<0.001) gender and age differences in bite incidents. Males were more at risk of dog bites than females, and the children aged 5–9 years were bitten more than other age groups, which substantiate our earlier findings of more use of PEP in males and children. The majority of victims were bitten by stray dogs, and the most common anatomical bite sites were on the legs. Using data on the anatomical location of dog bites in humans and a probability of dying from rabies, a decision tree model was constructed to estimate human deaths from rabies in two rabies endemic areas of southern Bhutan. Based on the official reported cases of rabies in two hospital areas (Gelephu and Phuentsholing) in southern Bhutan, the average number of human rabies death was 1.5 (95% CI: 0.75–3.00) per year, equivalent to an annual incidence of 3.14 (95% CI: 1.57–6.29) per 100,000 population. The decision tree model predicted 2.23 (95% CI: 1.20−3.59) human deaths from rabies per year, equivalent to an annual incidence of 4.67 (95% CI: 2.53–7.53) deaths per 100,000 populations. This indicated that no major underreporting of human rabies deaths has occurred, unlike in other rabies endemic countries, although some underreporting of dog bites is possible. In the absence of post-exposure prophylaxis, the model predicted 19.24 (95% CI: 13.69–25.14) deaths per year, equivalent to an annual incidence of 40.31 (95% CI: 28.70–52.68) per 100,000 population, suggesting post-exposure prophylaxis is important to prevent human rabies deaths. Since both dog bite incidents and the use of PEP were high in Bhutan, a cross-sectional study was conducted at Gelephu (south central Bhutan), an area endemic for rabies, to understand people’s level of knowledge and awareness about rabies. The study showed that a majority of the interviewed respondents had heard of rabies, and had a positive attitude towards the prevention and control of rabies. About 84 to 92% of the respondents also mentioned that they would report to the hospital for treatment if bitten by dogs and other animals, indicating good health seeking behaviours of the people. The respondents also had a positive attitude towards prevention and control of rabies in dogs by vaccination. However, these findings also indicated the existence of some knowledge gaps (knowledge about rabies and its transmission and importance of wound washing) which could be filled by creating awareness education programmes on: the danger of rabies and mode of transmission to humans and importance washing animal bite wound and visiting a hospital for post-exposure prophylaxis. Since rabies causes substantial financial losses to society, understanding the cost-benefit or cost-effectiveness of the intervention programme is important. Quantification of the financial cost of rabies intervention in Bhutan suggested that the average direct medical cost of human PEP (using rabies vaccine only) was approximately Bhutanese Ngultrum (Nu) 1615 (US$35.65) per 5-dose Essen regimen per patient. The cost would increase to Nu. 2497 (US$ 55.13) and Nu. 19633 (US$433.41) per patient, if one dose of either equine rabies immunoglobulin (ERIG) or human rabies immunoglobulin (HRIG) was administered, respectively. The societal cost (public plus private cost) per patient was estimated to be Nu. 2019 (US$ 45), Nu. 2901 (US$64), and Nu. 20037 (US$ 442) using vaccine alone, vaccine with ERIG and vaccine with HRIG, respectively. The average cost per dog vaccination was estimated to be Nu. 75 (US$1.66) and the cost per dog sterilization was estimated to be Nu. 288 (US$ 6.52). The total direct medical cost due to rabies (including surveillance and livestock loss cost, PEP in human and dog vaccination and sterilization) between 2001 and 2008 was estimated to be Nu. 48.54 million (US$ 1.07 million). The analysis also showed that mass dog vaccination would be more cost-effective than intensified post-exposure prophylaxis in human alone. The above findings suggest that an area bordering India in the south were at higher risk of reporting rabies than the interior of Bhutan. More resources for rabies control programs and surveillance should be targeted and focussed in the highly endemic ‘hot spot’ areas of southern Bhutan. Mass vaccination of dogs in the border areas in the south would create an immune buffer (cordon sanitaire) and prevent incursion of rabies into interior Bhutan. A One-Health approach for rabies control in Bhutan should be implemented towards elimination of rabies through creation of effective partnership focussing on coordinating research, operational activities and pooling of resources between public health and veterinary services. Elimination of rabies through mass dog vaccination would reduce the recurrent cost of intensified PEP in humans and will produce economic savings in the long run by preventing human and livestock deaths and by discontinuing the intensified use of PEP in humans and rabies control programmes. Public awareness education is necessary and should include: the risk of rabies exposure; importance of preventing dog bites and wound washing and visiting health centres following dog bites and exposure to suspected rabid animals. Epidemiological surveillance of rabies should be improved by the laboratory confirmation of all suspected cases, including human, and the data so generated should be shared between the public health and veterinary sectors and also relevant international organizations. International collaboration is necessary for technical and financial support for sustaining rabies control in Bhutan

Towards a self-disseminating vaccine to control vampire bat rabies in its reservoir

Viruses that circulate in wildlife can have devastating health and economic consequences when they enter human and livestock populations. Efforts to mitigate the burden of these zoonotic pathogens currently tend to focus on the spillover hosts; however, since this approach does not address the reservoir of disease, it prolongs the risk of re-emergence as viruses continue to circulate unimpeded in wildlife. Vaccination of wildlife reservoirs has the potential to prevent spillover, but is hampered by the logistical challenge of delivering vaccine to and achieving sufficient coverage in large, reclusive animal populations. Whilst orally available vaccines held inside edible baits have seen success in combating disease in some wildlife reservoirs, unique dietary requirements or behaviours can preclude the use of this strategy. The obligate blood-feeding common vampire bat Desmodus rotundus, reservoir host of rabies virus and primary source of rabies cases throughout Latin America, is one species in which edible baits are unsuitable, and other management strategies have thus far failed. Virally vectored transmissible vaccines which utilise the replicative capabilities of live viral vectors to spread autonomously between hosts, offer a potential solution. However, progress towards real world use of such vaccines is hampered by the selection of vaccine vectors which will prove both safe and efficacious. A betaherpesvirus recently identified in vampire bats (Desmodus rotundus betaherpesvirus; DrBHV) presents a promising candidate vector. In this thesis, I aimed to identify the key characteristics of DrBHV, and evaluate its biological and epidemiological suitability to vector a transmissible vaccine targeting rabies virus. The results presented here are based on field-collected samples, subjected to a combination of PCR, deep sequencing, and computer modelling. In Chapter 2, I aimed to assess the prevalence and host specificity of DrBHV, and the similarity of its genome composition to other betaherpesviruses currently considered for use as vaccine vectors. I used PCR to amplify a conserved region of the herpesvirus genome in saliva samples from Peruvian bats, with 96.9% of vampire bats testing positive, regardless of demographic group. Sanger sequencing of these regions and those from other positive bats revealed specificity of DrBHV to the Phyllostomidae family. Thus, DrBHV is able to spread efficiently within vampire bats, with only rare infection of closely related and cohabitating bat species. Metagenomic sequencing was able to construct a full genome consensus sequence for DrBHV similar in length and composition to betaherpesviruses in other species. This sequencing also showed the presence of multiple strain infections, suggesting that DrBHV may have the capacity to superinfect individuals, evading the host immune response. I aimed to further explore superinfection and DrBHV diversity in Chapter 3, by the amplification and deep sequencing of the highly variable gene encoding glycoprotein B. I identified eleven strains of DrBHV which varied in prevalence and geographic distribution across Peru. The phylogeographic structure of these strains was predictable from both host genetics and landscape topology, informing long-term DrBHV-vectored vaccine deployment strategies. Multi-strain infections were observed in 79% of infected bats and resampling of marked individuals showed strain acquisitions by already infected individuals, implying that pre-existing immunity and strain competition are unlikely to inhibit vaccine spread. Finally, in Chapter 4, I used the strain-specific prevalence data to fit models of DrBHV transmission. I identified the most likely model to include lifelong, persistent infection with cycles of latency and re-activation, a mechanism which would allow vaccinated individuals to boost their own immunity, and continually transmit vaccines to other bats throughout their lifetime. Simulations of vaccine spread show that a DrBHV-vectored vaccine can reach a population equilibrium coverage of >80% after a single introduction of vaccine, resulting in a 95% decrease in the size of rabies outbreaks. Furthermore, ongoing vaccine transmission is able to maintain these levels of vaccine coverage long-term, even in the presence of realistic levels of reversion, negating the need for recurrent and costly vaccination campaigns. In summary, the work presented in this thesis supports DrBHV as a candidate to vector a transmissible vaccine targeting a major source of rabies in Latin America and shows how accessible genomic data can enlighten vector selection and deployment strategies for transmissible vaccines. This work constitutes a fundamental step towards what would be the first deployment of a transmissible vaccine to prevent spillover of a zoonotic virus, thus allowing the management of disease to shift from reactive damage control to proactive prevention

Integrated disease surveillance and response systems in resource-limited settings

Infectious diseases are a major public health burden causing millions of deaths every year. Government authorities need to be able to monitor disease incidence and evaluate their interventions for disease control. Monitoring the status of infectious diseases is one of the most challenging problems facing the public health sector, and epidemiological surveillance systems for infectious diseases, particularly notifiable diseases are essential. Despite initiatives to encourage reporting of infectious diseases, underreporting and poor surveillance are on-going challenges for many developing countries. Most surveillance systems in these settings use traditional paper-based methods, which are both inefficient and impractical. There is a need for alternative tools to strengthen infectious disease surveillance systems in resource-limited settings. The remarkable progress made in mobile computing technology has the potential to improve infectious disease surveillance systems. However, user experience in digital technologies and infrastructure needs to be given greater attention. My study investigated the use of mobile phone devices as surveillance tools in health information systems. A mobile phone-based surveillance system was developed and applied in Tanzania as an alternative approach to traditional paper-based systems. Using this system different factors that affect the usability of mobile phone-based systems were investigated, by examining the quality of surveillance data in the context of completeness, timeliness and costs. After two years of operation in twenty-eight districts in southern Tanzania, numerous factors were identified that affect user accuracy and speed of use of the mobile phone-based surveillance. These include user experience in digital technology, particularly mobile device ownership; digital technology literacy, such as access and use of SMS and user’s age. The mobile phone-based surveillance system was more accurate compared to the traditional paper-based system with greater data reporting, more complete data and timelier reporting. Initially the mobile phone-based surveillance system required more capital investment, although the running costs of paper-based surveillance were greater. The utility of the mobile phone-based surveillance in monitoring and evaluating large-scale rabies control interventions was examined and the data produced was used to analyse the impacts of interventions on reducing disease incidence. Significant relationships were detected between the incidence of reported bite injuries in the focal district the previous month and in neighbouring districts that month, with more injuries detected in mainland Tanzania than on the island of Pemba. The relationship between bite injuries and vaccination coverage was complicated, with some evidence that vaccination reduced bite incidence. However, more data and a better model are needed to fully understand the impact of vaccination on bite incidence. The system provided timely information on the implementation of control measures and incidence of bite injuries, vital for improving control efforts. Use of automated short text messages (SMS) as part of the mobile phone-based surveillance was assessed to determine whether they could improve patient’s adherence to treatment regimens. Patients who received SMS reminders had significantly better compliance than those who did not, with attendance improved by at least 10%. Use of SMS reminders has the potential to improve patients’ compliance in other treatment regimens that require repeat clinic visits or administration of medicines. This thesis documented how the use of mobile phone devices can be used to improve surveillance in resource-limited settings. The use of effective integrated surveillance system could empower major stakeholders concerned with public health problems by providing them with appropriate real-time information on disease incidence and control interventions. In the final chapter the challenges encountered and insights gained in the application of mobile computing in strengthening infectious diseases surveillance are discussed. Despite infrastructural challenges such as unreliable power and Internet, mobile computing technologies can improve patient care and authorities can be prompted in a timely manner about infectious disease outbreaks and of supply shortages. In conclusion, innovative tools that can strengthen and integrate human and animal surveillance can improve the control and prevention of infectious diseases. Mobile phones have great potential for this, and can be used to strengthen health information systems