Crimean-Congo Hemorrhagic Fever Virus Seroprevalence in Human and Livestock Populations, Northern Tanzania.

We conducted a cross-sectional study of Crimean-Congo hemorrhagic fever virus (CCHFV) in northern Tanzania. CCHFV seroprevalence in humans and ruminant livestock was high, as were spatial heterogeneity levels. CCHFV could represent an unrecognized human health risk in this region and should be included as a differential diagnosis for febrile illness.

Population Structure and Antimicrobial Resistance in Campylobacter jejuni and C. coli Isolated from Humans with Diarrhea and from Poultry, East Africa.

Campylobacteriosis and antimicrobial resistance (AMR) are global public health concerns. Africa is estimated to have the world's highest incidence of campylobacteriosis and a relatively high prevalence of AMR in Campylobacter spp. from humans and animals. Few studies have compared Campylobacter spp. isolated from humans and poultry in Africa using whole-genome sequencing and antimicrobial susceptibility testing. We explored the population structure and AMR of 178 Campylobacter isolates from East Africa, 81 from patients with diarrhea in Kenya and 97 from 56 poultry samples in Tanzania, collected during 2006-2017. Sequence type diversity was high in both poultry and human isolates, with some sequence types in common. The estimated prevalence of multidrug resistance, defined as resistance to >3 antimicrobial classes, was higher in poultry isolates (40.9%, 95% credible interval 23.6%-59.4%) than in human isolates (2.5%, 95% credible interval 0.3%-6.8%), underlining the importance of antimicrobial stewardship in livestock systems.

Distemper, extinction, and vaccination of the Amur tiger.

Canine distemper virus (CDV) has recently emerged as an extinction threat for the endangered Amur tiger (Panthera tigris altaica). CDV is vaccine-preventable, and control strategies could require vaccination of domestic dogs and/or wildlife populations. However, vaccination of endangered wildlife remains controversial, which has led to a focus on interventions in domestic dogs, often assumed to be the source of infection. Effective decision making requires an understanding of the true reservoir dynamics, which poses substantial challenges in remote areas with diverse host communities. We carried out serological, demographic, and phylogenetic studies of dog and wildlife populations in the Russian Far East to show that a number of wildlife species are more important than dogs, both in maintaining CDV and as sources of infection for tigers. Critically, therefore, because CDV circulates among multiple wildlife sources, dog vaccination alone would not be effective at protecting tigers. We show, however, that low-coverage vaccination of tigers themselves is feasible and would produce substantive reductions in extinction risks. Vaccination of endangered wildlife provides a valuable component of conservation strategies for endangered species.

Global selective sweep of a highly inbred genome of the cattle parasite Neospora caninum.

Neospora caninum, a cyst-forming apicomplexan parasite, is a leading cause of neuromuscular diseases in dogs as well as fetal abortion in cattle worldwide. The importance of the domestic and sylvatic life cycles of Neospora, and the role of vertical transmission in the expansion and transmission of infection in cattle, is not sufficiently understood. To elucidate the population genomics of Neospora, we genotyped 50 isolates collected worldwide from a wide range of hosts using 19 linked and unlinked genetic markers. Phylogenetic analysis and genetic distance indices resolved a single genotype of N. caninum Whole-genome sequencing of 7 isolates from 2 different continents identified high linkage disequilibrium, significant structural variation, but only limited polymorphism genome-wide, with only 5,766 biallelic single nucleotide polymorphisms (SNPs) total. Greater than half of these SNPs (∼3,000) clustered into 6 distinct haploblocks and each block possessed limited allelic diversity (with only 4 to 6 haplotypes resolved at each cluster). Importantly, the alleles at each haploblock had independently segregated across the strains sequenced, supporting a unisexual expansion model that is mosaic at 6 genomic blocks. Integrating seroprevalence data from African cattle, our data support a global selective sweep of a highly inbred livestock pathogen that originated within European dairy stock and expanded transcontinentally via unisexual mating and vertical transmission very recently, likely the result of human activities, including recurrent migration, domestication, and breed development of bovid and canid hosts within similar proximities.

Spread of Nontyphoidal Salmonella in the Beef Supply Chain in Northern Tanzania: Sensitivity in a Probabilistic Model Integrating Microbiological Data and Data from Stakeholder Interviews.

East Africa is a hotspot for foodborne diseases, including infection by nontyphoidal Salmonella (NTS), a zoonotic pathogen that may originate from livestock. Urbanization and increased demand for animal protein drive intensification of livestock production and food processing, creating risks and opportunities for food safety. We built a probabilistic mathematical model, informed by prior beliefs and dedicated stakeholder interviews and microbiological research, to describe sources and prevalence of NTS along the beef supply chain in Moshi, Tanzania. The supply chain was conceptualized using a bow tie model, with terminal livestock markets as pinch point, and a forked pathway postmarket to compare traditional and emerging supply chains. NTS was detected in 36 (7.7%) of 467 samples throughout the supply chain. After combining prior belief and observational data, marginal estimates of true NTS prevalence were 4% in feces of cattle entering the beef supply and 20% in raw meat at butcheries. Based on our model and sensitivity analyses, true NTS prevalence was not significantly different between supply chains. Environmental contamination, associated with butchers and vendors, was estimated to be the most likely source of NTS in meat for human consumption. The model provides a framework for assessing the origin and propagation of NTS along meat supply chains. It can be used to inform decision making when economic factors cause changes in beef production and consumption, such as where to target interventions to reduce risks to consumers. Through sensitivity and value of information analyses, the model also helps to prioritize investment in additional research.

Investigating the Meat Pathway as a Source of Human Nontyphoidal Salmonella Bloodstream Infections and Diarrhea in East Africa.

BACKGROUND: Salmonella Enteritidis and Salmonella Typhimurium are major causes of bloodstream infection and diarrheal disease in East Africa. Sources of human infection, including the role of the meat pathway, are poorly understood. METHODS: We collected cattle, goat, and poultry meat pathway samples from December 2015 through August 2017 in Tanzania and isolated Salmonella using standard methods. Meat pathway isolates were compared with nontyphoidal serovars of Salmonella enterica (NTS) isolated from persons with bloodstream infections and diarrheal disease from 2007 through 2017 from Kenya by core genome multi-locus sequence typing (cgMLST). Isolates were characterized for antimicrobial resistance, virulence genes, and diversity. RESULTS: We isolated NTS from 164 meat pathway samples. Of 172 human NTS isolates, 90 (52.3%) from stool and 82 (47.7%) from blood, 53 (30.8%) were Salmonella Enteritidis sequence type (ST) 11 and 62 (36.0%) were Salmonella Typhimurium ST313. We identified cgMLST clusters within Salmonella Enteritidis ST11, Salmonella Heidelberg ST15, Salmonella Typhimurium ST19, and Salmonella II 42:r:- ST1208 that included both human and meat pathway isolates. Salmonella Typhimurium ST313 was isolated exclusively from human samples. Human and poultry isolates bore more antimicrobial resistance and virulence genes and were less diverse than isolates from other sources. CONCLUSIONS: Our findings suggest that the meat pathway may be an important source of human infection with some clades of Salmonella Enteritidis ST11 in East Africa, but not of human infection by Salmonella Typhimurium ST313. Research is needed to systematically examine the contributions of other types of meat, animal products, produce, water, and the environment to nontyphoidal Salmonella disease in East Africa.

Carnivore Parvovirus Ecology in the Serengeti Ecosystem: Vaccine Strains Circulating and New Host Species Identified.

Carnivore parvoviruses infect wild and domestic carnivores, and cross-species transmission is believed to occur. However, viral dynamics are not well understood, nor are the consequences for wild carnivore populations of the introduction of new strains into wild ecosystems. To clarify the ecology of these viruses in a multihost system such as the Serengeti ecosystem and identify potential threats for wildlife conservation, we analyzed, through real-time PCR, 152 samples belonging to 14 wild carnivore species and 62 samples from healthy domestic dogs. We detected parvovirus DNA in several wildlife tissues. Of the wild carnivore and domestic dog samples tested, 13% and 43%, respectively, were positive for carnivore parvovirus infection, but little evidence of transmission between the wild and domestic carnivores was detected. Instead, we describe two different epidemiological scenarios with separate routes of transmission: first, an endemic feline parvovirus (FPV) route of transmission maintained by wild carnivores inside the Serengeti National Park (SNP) and, second, a canine parvovirus (CPV) route of transmission among domestic dogs living around the periphery of the SNP. Twelve FPV sequences were characterized; new host-virus associations involving wild dogs, jackals, and hyenas were discovered; and our results suggest that mutations in the fragment of the vp2 gene were not required for infection of different carnivore species. In domestic dogs, 6 sequences belonged to the CPV-2a strain, while 11 belonged to the CPV-2 vaccine-derived strain. This is the first description of a vaccine-derived parvovirus strain being transmitted naturally.IMPORTANCE Carnivore parvoviruses are widespread among wild and domestic carnivores, which are vulnerable to severe disease under certain circumstances. This study furthers the understanding of carnivore parvovirus epidemiology, suggesting that feline parvoviruses are endemic in wild carnivores in the Serengeti National Park (SNP), with new host species identified, and that canine parvoviruses are present in the dog population living around the SNP. Little evidence of transmission of canine parvoviruses into wild carnivore species was found; however, the detection of vaccine-derived virus (described here for the first time to be circulating naturally in domestic dogs) highlights the importance of performing epidemiological research in the region.

Cross-species transmission and evolutionary dynamics of canine distemper virus during a spillover in African lions of Serengeti National Park.

The outcome of pathogen spillover from a reservoir to a novel host population can range from a "dead-end" when there is no onward transmission in the recipient population, to epidemic spread and even establishment in new hosts. Understanding the evolutionary epidemiology of spillover events leading to discrete outcomes in novel hosts is key to predicting risk and can lead to a better understanding of the mechanisms of emergence. Here we use a Bayesian phylodynamic approach to examine cross-species transmission and evolutionary dynamics during a canine distemper virus (CDV) spillover event causing clinical disease and population decline in an African lion population (Panthera leo) in the Serengeti Ecological Region between 1993 and 1994. Using 21 near-complete viral genomes from four species we found that this large-scale outbreak was likely  ignited by a single cross-species spillover event from a canid reservoir to noncanid hosts <1 year before disease detection and explosive spread of CDV in lions. Cross-species transmission from other noncanid species probably fuelled the high prevalence of CDV across spatially structured lion prides. Multiple lines of evidence suggest that spotted hyenas (Crocuta crocuta) could have acted as the proximate source of CDV exposure in lions. We report 13 nucleotide substitutions segregating CDV strains found in canids and noncanids. Our results are consistent with the hypothesis that virus evolution played a role in CDV emergence in noncanid hosts following spillover during the outbreak, suggest that host barriers to clinical infection can limit outcomes of CDV spillover in novel host species.

Transmission ecology of canine parvovirus in a multi-host, multi-pathogen system.

Understanding multi-host pathogen maintenance and transmission dynamics is critical for disease control. However, transmission dynamics remain enigmatic largely because they are difficult to observe directly, particularly in wildlife. Here, we investigate the transmission dynamics of canine parvovirus (CPV) using state-space modelling of 20 years of CPV serology data from domestic dogs and African lions in the Serengeti ecosystem. We show that, although vaccination reduces the probability of infection in dogs, and despite indirect enhancement of population seropositivity as a result of vaccine shedding, the vaccination coverage achieved has been insufficient to prevent CPV from becoming widespread. CPV is maintained by the dog population and has become endemic with approximately 3.5-year cycles and prevalence reaching approximately 80%. While the estimated prevalence in lions is lower, peaks of infection consistently follow those in dogs. Dogs exposed to CPV are also more likely to become infected with a second multi-host pathogen, canine distemper virus. However, vaccination can weaken this coupling, raising questions about the value of monovalent versus polyvalent vaccines against these two pathogens. Our findings highlight the need to consider both pathogen- and host-level community interactions when seeking to understand the dynamics of multi-host pathogens and their implications for conservation, disease surveillance and control programmes.

An integrated health delivery platform, targeting soil-transmitted helminths (STH) and canine mediated human rabies, results in cost savings and increased breadth of treatment for STH in remote communities in Tanzania.

BACKGROUND: Achieving the Sustainable Development Goal of a 90% reduction in neglected tropical diseases (NTDs) by 2030 requires innovative control strategies. This proof-of-concept study examined the effectiveness of integrating control programs for two NTDs: mass drug administration (MDA) for soil-transmitted helminths in humans and mass dog rabies vaccination (MDRV). METHODS: The study was carried out in 24 Tanzanian villages. The primary goal was to demonstrate the feasibility of integrating community-wide MDA for STH and MDRV for rabies. The objectives were to investigate the popularity, participation and cost and time savings of integrated delivery, and to investigate the reach of the MDA with respect to primary school-aged children and other community members. To implement, we randomly allocated villages for delivery of MDA and MDRV (Arm A), MDA only (Arm B) or MDRV only (Arm C). RESULTS: Community support for the integrated delivery was strong (e.g. 85% of focus group discussions concluded that it would result in people getting "two for one" health treatments). A high proportion of households participated in the integrated Arm A events (81.7% MDA, 80.4% MDRV), and these proportions were similar to those in Arms B and C. These findings suggest that coverage might not be reduced when interventions are integrated. Moreover, in addition to time savings, integrated delivery resulted in a 33% lower cost per deworming dose and a 16% lower cost per rabies vaccination. The median percentage of enrolled primary school children treated by this study was 76%. However, because 37% of the primary school aged children that received deworming treatment were not enrolled in school, we hypothesize that the employed strategy could reach more school-aged children than would be reached through a solely school-based delivery strategy. CONCLUSIONS: Integrated delivery platforms for health interventions can be feasible, popular, cost and time saving. The insights gained could be applicable in areas of sub-Saharan Africa that are remote or underserved by health services. These results indicate the utility of integrated One Health delivery platforms and suggest an important role in the global campaign to reduce the burden of NTDs, especially in hard-to-reach communities. TRIAL REGISTRATION: clinicaltrials.gov NCT03667079 , retrospectively registered 11th September 2018.

Dynamics of a morbillivirus at the domestic-wildlife interface: Canine distemper virus in domestic dogs and lions.

Morbilliviruses cause many diseases of medical and veterinary importance, and although some (e.g., measles and rinderpest) have been controlled successfully, others, such as canine distemper virus (CDV), are a growing concern. A propensity for host-switching has resulted in CDV emergence in new species, including endangered wildlife, posing challenges for controlling disease in multispecies communities. CDV is typically associated with domestic dogs, but little is known about its maintenance and transmission in species-rich areas or about the potential role of domestic dog vaccination as a means of reducing disease threats to wildlife. We address these questions by analyzing a long-term serological dataset of CDV in lions and domestic dogs from Tanzania's Serengeti ecosystem. Using a Bayesian state-space model, we show that dynamics of CDV have changed considerably over the past three decades. Initially, peaks of CDV infection in dogs preceded those in lions, suggesting that spill-over from dogs was the main driver of infection in wildlife. However, despite dog-to-lion transmission dominating cross-species transmission models, infection peaks in lions became more frequent and asynchronous from those in dogs, suggesting that other wildlife species may play a role in a potentially complex maintenance community. Widespread mass vaccination of domestic dogs reduced the probability of infection in dogs and the size of outbreaks but did not prevent transmission to or peaks of infection in lions. This study demonstrates the complexity of CDV dynamics in natural ecosystems and the value of long-term, large-scale datasets for investigating transmission patterns and evaluating disease control strategies.

Rabies elimination research: juxtaposing optimism, pragmatism and realism.

More than 100 years of research has now been conducted into the prevention, control and elimination of rabies with safe and highly efficacious vaccines developed for use in human and animal populations. Domestic dogs are a major reservoir for rabies, and although considerable advances have been made towards the elimination and control of canine rabies in many parts of the world, the disease continues to kill tens of thousands of people every year in Africa and Asia. Policy efforts are now being directed towards a global target of zero human deaths from dog-mediated rabies by 2030 and the global elimination of canine rabies. Here we demonstrate how research provides a cause for optimism as to the feasibility of these goals through strategies based around mass dog vaccination. We summarize some of the pragmatic insights generated from rabies epidemiology and dog ecology research that can improve the design of dog vaccination strategies in low- and middle-income countries and which should encourage implementation without further delay. We also highlight the need for realism in reaching the feasible, although technically more difficult and longer-term goal of global elimination of canine rabies. Finally, we discuss how research on rabies has broader relevance to the control and elimination of a suite of diseases of current concern to human and animal health, providing an exemplar of the value of a 'One Health' approach.

Scoping review of indicators and methods of measurement used to evaluate the impact of dog population management interventions.

BACKGROUND: Dogs are ubiquitous in human society and attempts to manage their populations are common to most countries. Managing dog populations is achieved through a range of interventions to suit the dog population dynamics and dog ownership characteristics of the location, with a number of potential impacts or goals in mind. Impact assessment provides the opportunity for interventions to identify areas of inefficiencies for improvement and build evidence of positive change. METHODS: This scoping review collates 26 studies that have assessed the impacts of dog population management interventions. RESULTS: It reports the use of 29 indicators of change under 8 categories of impact and describes variation in the methods used to measure these indicators. CONCLUSION: The relatively few published examples of impact assessment in dog population management suggest this field is in its infancy; however this review highlights those notable exceptions. By describing those indicators and methods of measurement that have been reported thus far, and apparent barriers to efficient assessment, this review aims to support and direct future impact assessment.

Mobile Phones As Surveillance Tools: Implementing and Evaluating a Large-Scale Intersectoral Surveillance System for Rabies in Tanzania.

Katie Hampson and colleagues describe their experience of developing and deploying a large-scale rabies surveillance system based on mobile phones in southern Tanzania.

Integrating serological and genetic data to quantify cross-species transmission: brucellosis as a case study.

Epidemiological data are often fragmented, partial, and/or ambiguous and unable to yield the desired level of understanding of infectious disease dynamics to adequately inform control measures. Here, we show how the information contained in widely available serology data can be enhanced by integration with less common type-specific data, to improve the understanding of the transmission dynamics of complex multi-species pathogens and host communities. Using brucellosis in northern Tanzania as a case study, we developed a latent process model based on serology data obtained from the field, to reconstruct Brucella transmission dynamics. We were able to identify sheep and goats as a more likely source of human and animal infection than cattle; however, the highly cross-reactive nature of Brucella spp. meant that it was not possible to determine which Brucella species (B. abortus or B. melitensis) is responsible for human infection. We extended our model to integrate simulated serology and typing data, and show that although serology alone can identify the host source of human infection under certain restrictive conditions, the integration of even small amounts (5%) of typing data can improve understanding of complex epidemiological dynamics. We show that data integration will often be essential when more than one pathogen is present and when the distinction between exposed and infectious individuals is not clear from serology data. With increasing epidemiological complexity, serology data become less informative. However, we show how this weakness can be mitigated by integrating such data with typing data, thereby enhancing the inference from these data and improving understanding of the underlying dynamics.

Cost-effectiveness of canine vaccination to prevent human rabies in rural Tanzania.

BACKGROUND: The annual mortality rate of human rabies in rural Africa is 3.6 deaths per 100 000 persons. Rabies can be prevented with prompt postexposure prophylaxis, but this is costly and often inaccessible in rural Africa. Because 99% of human exposures occur through rabid dogs, canine vaccination also prevents transmission of rabies to humans. OBJECTIVE: To evaluate the cost-effectiveness of rabies control through annual canine vaccination campaigns in rural sub-Saharan Africa. DESIGN: We model transmission dynamics in dogs and wildlife and assess empirical uncertainty in the biological variables to make probability-based evaluations of cost-effectiveness. DATA SOURCES: Epidemiologic variables from a contact-tracing study and literature and cost data from ongoing vaccination campaigns. TARGET POPULATION: Two districts of rural Tanzania: Ngorongoro and Serengeti. TIME HORIZON: 10 years. PERSPECTIVE: Health policymaker. INTERVENTION: Vaccination coverage ranging from 0% to 95% in increments of 5%. OUTCOME MEASURES: Life-years for health outcomes and 2010 U.S. dollars for economic outcomes. RESULTS OF BASE-CASE ANALYSIS: Annual canine vaccination campaigns were very cost-effective in both districts compared with no canine vaccination. In Serengeti, annual campaigns with as much as 70% coverage were cost-saving. RESULTS OF SENSITIVITY ANALYSIS: Across a wide range of variable assumptions and levels of societal willingness to pay for life-years, the optimal vaccination coverage for Serengeti was 70%. In Ngorongoro, although optimal coverage depended on willingness to pay, vaccination campaigns were always cost-effective and lifesaving and therefore preferred. LIMITATION: Canine vaccination was very cost-effective in both districts, but there was greater uncertainty about the optimal coverage in Ngorongoro. CONCLUSION: Annual canine rabies vaccination campaigns conferred extraordinary value and dramatically reduced the health burden of rabies. PRIMARY FUNDING SOURCE: National Institutes of Health.

Antigenic and genetic characterization of a divergent African virus, Ikoma lyssavirus.

In 2009, a novel lyssavirus (subsequently named Ikoma lyssavirus, IKOV) was detected in the brain of an African civet (Civettictis civetta) with clinical rabies in the Serengeti National Park of Tanzania. The degree of nucleotide divergence between the genome of IKOV and those of other lyssaviruses predicted antigenic distinction from, and lack of protection provided by, available rabies vaccines. In addition, the index case was considered likely to be an incidental spillover event, and therefore the true reservoir of IKOV remained to be identified. The advent of sensitive molecular techniques has led to a rapid increase in the discovery of novel viruses. Detecting viral sequence alone, however, only allows for prediction of phenotypic characteristics and not their measurement. In the present study we describe the in vitro and in vivo characterization of IKOV, demonstrating that it is (1) pathogenic by peripheral inoculation in an animal model, (2) antigenically distinct from current rabies vaccine strains and (3) poorly neutralized by sera from humans and animals immunized against rabies. In a laboratory mouse model, no protection was elicited by a licensed rabies vaccine. We also investigated the role of bats as reservoirs of IKOV. We found no evidence for infection among 483 individuals of at least 13 bat species sampled across sites in the Serengeti and Southern Kenya.

Empirical and model-based evidence for a negligible role of cattle in peste des petits ruminants virus transmission and eradication.

Peste des petits ruminants virus (PPRV) is a multi-host pathogen with sheep and goats as main hosts. To investigate the role of cattle in the epidemiology of PPR, we simulated conditions similar to East African zero-grazing husbandry practices in a series of trials with local Zebu cattle (Bos taurus indicus) co-housed with goats (Capra aegagrus hircus). Furthermore, we developed a mathematical model to assess the impact of PPRV-transmission from cattle to goats. Of the 32 cattle intranasally infected with the locally endemic lineage IV strain PPRV/Ethiopia/Habru/2014 none transmitted PPRV to 32 co-housed goats. However, these cattle or cattle co-housed with PPRV-infected goats seroconverted. The results confirm previous studies that cattle currently play a negligible role in PPRV-transmission and small ruminant vaccination is sufficient for eradication. However, the possible emergence of PPRV strains more virulent for cattle may impact eradication. Therefore, continued monitoring of PPRV circulation and evolution is recommended.

Peste des petits ruminants infection among cattle and wildlife in northern Tanzania.

We investigated peste des petits ruminants (PPR) infection in cattle and wildlife in northern Tanzania. No wildlife from protected ecosystems were seropositive. However, cattle from villages where an outbreak had occurred among small ruminants showed high PPR seropositivity, indicating that spillover infection affects cattle. Thus, cattle could be of value for PPR serosurveillance.