Transmission dynamics and prospects for the elimination of canine rabies

Rabies has been eliminated from domestic dog populations in Western Europe and North America, but continues to kill many thousands of people throughout Africa and Asia every year. A quantitative understanding of transmission dynamics in domestic dog populations provides critical information to assess whether global elimination of canine rabies is possible. We report extensive observations of individual rabid animals in Tanzania and generate a uniquely detailed analysis of transmission biology, which explains important epidemiological features, including the level of variation in epidemic trajectories. We found that the basic reproductive number for rabies, R<sub>0</sub>, is very low in our study area in rural Africa (∼1.2) and throughout its historic global range (<2). This finding provides strong support for the feasibility of controlling endemic canine rabies by vaccination, even near wildlife areas with large wild carnivore populations. However, we show that rapid turnover of domestic dog populations has been a major obstacle to successful control in developing countries, thus regular pulse vaccinations will be required to maintain population-level immunity between campaigns. Nonetheless our analyses suggest that with sustained, international commitment, global elimination of rabies from domestic dog populations, the most dangerous vector to humans, is a realistic goal

Reservoir dynamics of rabies in Southeast Tanzania and the roles of cross-species transmission and domestic dog vaccination

1) Understanding the role of different species in the transmission of multi-host pathogens, such as rabies virus, is vital for effective control strategies. Across most of sub-Saharan Africa domestic dogs (Canis familiaris) are considered the reservoir for rabies, but the role of wildlife has been long debated. Here we explore the multi-host transmission dynamics of rabies across southeast Tanzania. 2) Between January 2011 and July 2019 data on probable rabies cases were collected in the regions of Lindi and Mtwara. Hospital records of animal-bite patients presenting to healthcare facilities were used as sentinels for animal contact tracing. The timing, location and species of probable rabid animals was used to reconstruct transmission trees to infer who infected whom and the relative frequencies of within-and between-species transmission. 3) During the study, 688 probable human rabies exposures were identified, resulting in 47 deaths. Of these exposures, 389 were from domestic dogs (56.5%) and 262 from jackals (38.1%). Over the same period 549 probable animal rabies cases were traced: 303 in domestic dogs (55.2%) and 221 in jackals (40.3%). 4) Although dog-to-dog transmission was most commonly inferred (40.5% of transmission events), a third of inferred events involved wildlife-to-wildlife transmission (32.6%) and evidence suggested some sustained transmission chains within jackal populations. 5) A steady decline in probable rabies cases in both humans and animals coincided with the implementation of widespread domestic dog vaccination during the first six years of the study. Following the lapse of this programme dog rabies cases began to increase in one of the northernmost districts. 6) Synthesis and applications: in southeast Tanzania, despite a relatively high incidence of rabies in wildlife and evidence of wildlife-to-wildlife transmission, domestic dogs remain essential to the reservoir of infection. Continued dog vaccination alongside improved surveillance would allow a fuller understanding of the role of wildlife in maintaining transmission in this area. Nonetheless, dog vaccination clearly suppressed rabies in both domestic dog and wildlife populations, reducing both public health and conservation risks and, if sustained, has potential to eliminate rabies from this region

The feasibility of canine rabies elimination in Africa: dispelling doubts with data

<p><b>Background:</b> Canine rabies causes many thousands of human deaths every year in Africa, and continues to increase throughout much of the continent.</p> <p><b>Methodology/Principal Findings:</b> 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.</p> <p><b>Conclusions/Significance:</b> 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.</p&gt

Effect of direct-current magnetic field on the specific absorption rate of metamagnetic CoMnSi: A potential approach to switchable hyperthermia therapy

Materials with 1st order antiferromagnetic (AFM) to high-magnetization (MM) phase transition known for their inverse magnetocaloric effect, abrupt rise in magnetization and magnetoelastic coupling, are promising for application in combined simultaneous diagnosis and targeted cancer therapy. A therapy that combines alternating-current (ac) and direct-current (dc) magnetic fields for simultaneous magnetic hyperthermia therapy (MHT) and magnetic resonance imaging (MRI), using same magnetic particles for heating and as con- trast agents. We report a proof-of-concept study on the induction heating ability of 1st order metamagnetic material with moderate specific absorption rates (SAR) and no tendency for agglomeration, for potential MHT and MRI cancer therapy. CoMnSi, a metam- agnetic antiferromagnet (MM) was used in this study because of its desirable ability to rapidly switch from a low to high magnetiza- tion state in an applied dc bias field condition without particle agglomeration on field removal. The results showed that the magne- tization switched from \u3c 20 Am2kg-1 at 0.75 T to about 53.31 Am2kg-1 at 1.0 T applied dc field, a field large enough for magnetic resonance imaging. An SAR value of 10.7 Wg-1 was obtained under an ac field of 31.0 kAm-1 at 212.0 kHz. When combined with a dc bias field of 1.0 T, SAR values of 9.83 Wg-1 and 6.65 Wg-1 were obtained in the directions 45○ and 90○ away from the dc bias field direction respectively. These SAR values obtained from CoMnSi particles in the presence of simultaneous ac and dc magnetic field bias are in comparison, at least 25 times greater than those obtained from 2nd order magnetic phase transition Fe3O4 suspension. It is observed that Fe3O4 particles showed large suppression of SAR, and agglomeration under the same experimental conditions. This study shows the great potential of 1st order phase transition metamagnets for simultaneous MHT and MRI cancer therapy using MRI equipment

Evolutionary relationships among barley and <i>Arabidopsis</i> core circadian clock and clock-associated genes

The circadian clock regulates a multitude of plant developmental and metabolic processes. In crop species, it contributes significantly to plant performance and productivity and to the adaptation and geographical range over which crops can be grown. To understand the clock in barley and how it relates to the components in the Arabidopsis thaliana clock, we have performed a systematic analysis of core circadian clock and clock-associated genes in barley, Arabidopsis and another eight species including tomato, potato, a range of monocotyledonous species and the moss, Physcomitrella patens. We have identified orthologues and paralogues of Arabidopsis genes which are conserved in all species, monocot/dicot differences, species-specific differences and variation in gene copy number (e.g. gene duplications among the various species). We propose that the common ancestor of barley and Arabidopsis had two-thirds of the key clock components identified in Arabidopsis prior to the separation of the monocot/dicot groups. After this separation, multiple independent gene duplication events took place in both monocot and dicot ancestors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00239-015-9665-0) contains supplementary material, which is available to authorized users

Designing programs for eliminating canine rabies from islands: Bali, Indonesia as a case study

&lt;p&gt;Background: Canine rabies is one of the most important and feared zoonotic diseases in the world. In some regions rabies elimination is being successfully coordinated, whereas in others rabies is endemic and continues to spread to uninfected areas. As epidemics emerge, both accepted and contentious control methods are used, as questions remain over the most effective strategy to eliminate rabies. The Indonesian island of Bali was rabies-free until 2008 when an epidemic in domestic dogs began, resulting in the deaths of over 100 people. Here we analyze data from the epidemic and compare the effectiveness of control methods at eliminating rabies.&lt;/p&gt; &lt;p&gt;Methodology/Principal Findings: Using data from Bali, we estimated the basic reproductive number, R0, of rabies in dogs, to be ~1·2, almost identical to that obtained in ten–fold less dense dog populations and suggesting rabies will not be effectively controlled by reducing dog density. We then developed a model to compare options for mass dog vaccination. Comprehensive high coverage was the single most important factor for achieving elimination, with omission of even small areas (&#60;0.5% of the dog population) jeopardizing success. Parameterizing the model with data from the 2010 and 2011 vaccination campaigns, we show that a comprehensive high coverage campaign in 2012 would likely result in elimination, saving ~550 human lives and ~$15 million in prophylaxis costs over the next ten years.&lt;/p&gt; &lt;p&gt;Conclusions/Significance: The elimination of rabies from Bali will not be achieved through achievable reductions in dog density. To ensure elimination, concerted high coverage, repeated, mass dog vaccination campaigns are necessary and the cooperation of all regions of the island is critical. Momentum is building towards development of a strategy for the global elimination of canine rabies, and this study offers valuable new insights about the dynamics and control of this disease, with immediate practical relevance.&lt;/p&gt

Tandem quadruplication of HMA4 in the zinc (Zn) and cadmium (Cd) hyperaccumulator noccaea caerulescens

Zinc (Zn) and cadmium (Cd) hyperaccumulation may have evolved twice in the Brassicaceae, in Arabidopsis halleri and in the Noccaea genus. Tandem gene duplication and deregulated expression of the Zn transporter, HMA4, has previously been linked to Zn/Cd hyperaccumulation in A. halleri. Here, we tested the hypothesis that tandem duplication and deregulation of HMA4 expression also occurs in Noccaea. A Noccaea caerulescens genomic library was generated, containing 36,864 fosmid pCC1FOSTM clones with insert sizes ~20–40 kbp, and screened with a PCR-generated HMA4 genomic probe. Gene copy number within the genome was estimated through DNA fingerprinting and pooled fosmid pyrosequencing. Gene copy numbers within individual clones was determined by PCR analyses with novel locus specific primers. Entire fosmids were then sequenced individually and reads equivalent to 20-fold coverage were assembled to generate complete whole contigs. Four tandem HMA4 repeats were identified in a contiguous sequence of 101,480 bp based on sequence overlap identities. These were flanked by regions syntenous with up and downstream regions of AtHMA4 in Arabidopsis thaliana. Promoter-reporter b-glucuronidase (GUS) fusion analysis of a NcHMA4 in A. thaliana revealed deregulated expression in roots and shoots, analogous to AhHMA4 promoters, but distinct from AtHMA4 expression which localised to the root vascular tissue. This remarkable consistency in tandem duplication and deregulated expression of metal transport genes between N. caerulescens and A. halleri, which last shared a common ancestor >40 mya, provides intriguing evidence that parallel evolutionary pathways may underlie Zn/Cd hyperaccumulation in Brassicaceae

Evaluating the potential for the environmentally sustainable control of foot and mouth disease in Sub-Saharan Africa

Strategies to control transboundary diseases have in the past generated unintended negative consequences for both the environment and local human populations. Integrating perspectives from across disciplines, including livestock, veterinary and conservation sectors, is necessary for identifying disease control strategies that optimise environmental goods and services at the wildlife-livestock interface. Prompted by the recent development of a global strategy for the control and elimination of foot-and-mouth disease (FMD), this paper seeks insight into the consequences of, and rational options for potential FMD control measures in relation to environmental, conservation and human poverty considerations in Africa. We suggest a more environmentally nuanced process of FMD control that safe-guards the integrity of wild populations and the ecosystem dynamics on which human livelihoods depend while simultaneously improving socio-economic conditions of rural people. In particular, we outline five major issues that need to be considered: 1) improved understanding of the different FMD viral strains and how they circulate between domestic and wildlife populations; 2) an appreciation for the economic value of wildlife for many African countries whose presence might preclude the country from ever achieving an FMD-free status; 3) exploring ways in which livestock production can be improved without compromising wildlife such as implementing commodity-based trading schemes; 4) introducing a participatory approach involving local farmers and the national veterinary services in the control of FMD; and 5) finally the possibility that transfrontier conservation might offer new hope of integrating decision-making at the wildlife-livestock interface

Determining the Effects of Tryptophan Biomass on Growth Performance of 25- to 50-lb Nursery Pigs

A total of 315 barrows (DNA; 200 × 400; initially 24.9 lb) were used in a 21-d growth trial evaluating the effects of feeding TRP Pro (CJ America-Bio, Downers Grove, IL) as a source of Trp on nursery pig performance. Pigs were weaned at approximately 21 d of age, placed in pens based on initial body weight (BW), and fed common starter diets for 21 d. On d 21 after weaning, considered d 0 of the study, pigs were weighed and pens were allotted to 1 of 4 dietary treatments with 5 pigs per pen and 15 or 16 pens per treatment. Dietary treatments included a negative control (16% SID Trp:Lys ratio), positive control (21% SID Trp:Lys ratio from crystalline Trp), or diets containing Trp with biomass to provide 21 or 23.5% standardized ileal digestible (SID) Trp:Lys ratios (included at 0.104 or 0.156% of the diet, respectively). Diets were corn-soybean meal-based and contained 1.25% SID Lys with other amino acids set to meet or exceed NRC requirement estimates. The TRP Pro contained 60% Trp per the supplier’s specifications. Growth data were analyzed as a randomized complete block design using the PROC GLIMMIX procedure of SAS with pen as the experimental unit. Overall (d 0 to 21), pigs fed the 21% Trp:Lys ratio from crystalline Trp or Trp with biomass had increased (P \u3c 0.05) average daily gain (ADG) compared to pigs fed the negative control diet, with pigs fed the 23.5% Trp:Lys ratio with biomass intermediate. There was no evidence for difference in overall average daily feed intake (ADFI); however, pigs fed the 21% Trp:Lys ratio from Trp with biomass had improved (P \u3c 0.05) feed efficiency (F/G) compared to the negative control diet, with others intermediate. In conclusion, TRP Pro appears to be a suitable alternative to crystalline Trp in nursery pig diets but further evaluation at higher inclusion levels is needed

Improving Performance of Finishing Pigs with Added Valine, Isoleucine, and Tryptophan: Validating a Meta-Analysis Model

Based on a recent meta-analysis, we hypothesized that increased dietary Val, Ile, or Trp could correct possible amino acid interactions caused by high dietary Leu in diets containing high levels of corn protein, namely dried distillers grains with solubles (DDGS). A total of 1,200 pigs (PIC TR4 × (Fast LW × PIC L02); initially 74.0 ± 1.38 lb) were used in a 103-d study. The 6 dietary treatments were corn-soybean meal- DDGS-based diets as follows: 1) low level of Lys-HCl (HSBM), 2) high Lys-HCl and moderate Ile, Val, Trp (NC; AA above NRC4 estimates), 3) moderate Lys-HCl and high Ile, Val, Trp (PC), and 4) PC with either increased L-Val (PC+Val), 5) L-Ile (PC+Ile), or 6) L-Trp (PC+Trp). Diets contained 30% DDGS until pigs reached approximately 217 lb, and then pigs were fed diets with 20% DDGS until market. Data were analyzed as a randomized complete block design using the lmer function in the lme4 package in R with pen considered as the experimental unit, body weight, and pen location as a blocking factor, and treatment as a fixed effect with 10 replicates/treatment. In the grower period, ADG was greater (P \u3c 0.05) for the pigs fed HSBM and PC+Val diets than the NC with PC, PC+Ile, and PC+Trp intermediate. Pigs fed HSBM were more (P \u3c 0.05) efficient than the NC and PC with PC+Val, PC+Ile, and PC+Trp being intermediate. In the late finisher period, ADG was greater (P \u3c 0.05) for pigs fed PC+Ile than that of the NC with HSBM, PC, PC+Val, and PC+Trp intermediate. Pigs fed PC+Val had greater (P \u3c 0.05) ADFI than the NC with HSBM, PC, PC+Ile, and PC+Trp being intermediate. However, PC+Ile pigs were more (P \u3c 0.05) efficient than PC+Val pigs with HSBM, NC, PC, and PC+Trp being intermediate. Overall, final body weight (BW), average daily gain (ADG), and hot carcass weight (HCW) were greater (P \u3c 0.05) for pigs fed HSBM, PC+Val, and PC+Ile diets than the NC with PC and PC+Trp intermediate. Pigs fed the PC+Val diet had greater (P \u3c 0.05) average daily feed intake (ADFI) than the NC with pigs fed HSBM, PC, PC+Ile, and PC+Trp intermediate. No differences were detected between treatments for overall F/G or other carcass characteristics. In conclusion, increasing Val or Ile in high Lys- HCl-DDGS-based diets improved growth performance and final BW compared with pigs fed diets containing high levels of Lys-HCl without added Val and Ile. These results demonstrate that the negative effects of high Leu concentrations in corn-DDGS-based diets can be corrected by increasing the ratios of Val and Ile to Lys