Hydrophobia

The GBD study provides a standardised analytical approach for estimating incidence, prevalence, and YLDs by age, sex, cause, year, and location. We aim to use all accessible information on disease occurrence, natural history, and severity that passes minimum inclusion criteria set disease-by-disease (appendix 1, p 33). Our approach is to optimise the comparability of data collected by varying methods or different case definitions; find a consistent set of estimates between data for prevalence, incidence, and causes of death; and predict estimates for locations with sparse or absent data by borrowing information from other locations and using covariates.
In this study, we use different methods to reflect the available data and specific epidemiology of each disease. Our main approach is to combine all sources of information for a disease using the Bayesian meta-regression tool DisMod-MR 2.1.¹⁶ Subsequently, we use data for severity, the occurrence of particular consequences of diseases, or sequelae, to establish the proportion of prevalent cases experiencing each sequela. Several broad classes of alternative approaches are used within the GBD study. First, for injuries, non-fatal estimates must account for the cause of injury (eg, a fall), the nature of injury (eg, a fracture or head injury), the amount of disability arising in the short term, and permanent disability for a subset of cases. Second, cancers were estimated by assessing the association between mortality and incidence, taking into account the effect on survival of access to, and quality of, treatment for the cancer site. Third, we combined the natural history model strategy for HIV/AIDS with the DisMod-MR 2.1 modelling approach for tuberculosis as HIV infection affects outcomes in patients who also have tuberculosis. Fourth, models for malaria, hepatitis, and varicella relied on data of the presence of circulating antibodies or parasites in the blood to predict the incidence of clinical episodes for which we estimate disability. Fifth, neonatal disorders were estimated from birth prevalence data and cohort studies on the risk of death in the first month and the probability of long-term disabling outcomes. Sixth, incidence of rabies, whooping cough, diphtheria, and tetanus was estimated from cause-specific mortality rates and data on the case fatality of acute episodes (appendix 1, p 33).
Below we describe these modelling efforts organised into eight sections; the supplementary methods (appendix 1, p 1) presents a single source for additional detail of inputs, analytical processes, outputs, and methods specific to each cause. This study complies with the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER) recommendations (appendix 1, p 723).¹⁷ (link)

The mAb CR3014 was isolated from a semisynthetic single-chain variable antibody fragment (scFv) phage display library, expressed as human IgG1 molecules and purified as described previously [
22 (link),
27 (link)]. An immune scFv phage display library was constructed from lymphocytes of a convalescent SARS patient from Singapore essentially as described [
28 (link)]. From this library, CR3022 scFv was selected for binding to UV-inactivated SARS-CoV, essentially as described [
22 (link)]. SARS-CoV (Frankfurt 1 strain [FM1]) was prepared as described and UV-irradiated for 15 min (UVB radiation, 280–350 nm; λ
_max, 306 nm) at 4 °C. CR3022 scFv was converted into a human IgG1 format and expressed and purified as described. Anti-rabies mAb CRJA served as negative control.

From 4 healthy experimental Beagle dogs (Table 1, one female, three male, age: 5 – 9 years) of the Faculty of Veterinary Medicine (Leipzig University, Leipzig, Germany), venous blood was taken by venipuncture of the vena cephalica antebrachii into heparinized vacutainer tubes (BD Vacutainer^®, 10 ml, Li-Heparin 17 IU/ml Becton Dickinson, Heidelberg, Germany). All dogs received routine vaccinations against canine distemper, rabies, canine infectious hepatitis, parvovirus infection, parainfluenza, and leptospirosis. The study was authorized by the Saxony State Office (Landesdirektion Sachsen) in Leipzig, Germany (approval number: DD24.1-5131/444/30).

Echinococcus multilocularis specimens were collected from gastrointestinal (GI) tracts of red foxes and coyotes of either road-killed or trap-harvested animals (trapped for purposes independent of this study), collected between 2012 and 2017 in Western Canada. Trapped animals were obtained from licensed trappers with the collaboration of the Alberta Trappers Association. GI tracts were screened using a modification of the scraping, filtration and counting technique, to identify and collect Echinococcus spp. worms [35 (link),36 (link)]. We analysed Em worms from 70 coyotes and 13 foxes from northern, central and southern Alberta (AB); four coyotes from north-west British Columbia (BC); and 10 coyotes from southeast Saskatchewan (SK). Extraction of DNA was performed on up to five individual worms per host using the Nucleospin 96 Tissue Kit (Macherey-Nagel, Germany) for samples processed in France (Anses Nancy Laboratory for Rabies and Wildlife) and the E.Z.N.A. MicroElute Genomic DNA Kit (Omega Bio-tek, US) for samples processed in Canada (University of Calgary, Faculty of Veterinary Medicine). Extraction was performed following the manufacturer's instructions, and DNA was stored at −20°C until processed.

This study took place in two Indigenous communities and one administrative municipality located in northern Quebec, Canada: Kawawachikamach (KWW), Matimekush-Lac John (MLJ), and Schefferville (SCH). KWW is the only Naskapi community in Canada and is located 15 km from MLJ and SCH. MLJ is an Innu community surrounded by the territory of SCH (Figure 1A). They are located above the 54th parallel and can only be reached by train or plane (Figure 1B). According to the last census in 2016, the population is 601 inhabitants in KWW (28 ), 613 in MLJ (29 ), and 155 in SCH (30 ). Indigenous people represent 99.2% of inhabitants in KWW (28 ), 94.3% in MLJ (29 ), and 48.4% in SCH (30 ).
Naskapi from KWW are under the James Bay and Northern Québec agreement. This agreement between governments of Quebec and Canada and some Indigenous nations was signed in order to redefine the organization of the territory and its administration (31 ). Innu from MLJ are under the Indian Act. Only beneficiary Indigenous communities of the James Bay and Northern Québec agreement, either Inuit, Cree and Naskapi, are illegible for the Quebec government vaccination program for northern communities for the protection of dogs against rabies (32 ).
This study was part of a larger project called Balancing Illness and Wellness at the Human-Dog Interface in Northern Canada, which aims to investigate the relationships between dogs, humans and their respective health in Canada, using the “two-eyes” model that combines Indigenous knowledge and Western science. It also aims to propose, implement and evaluate solutions to reduce the risks at the human-dog interface while promoting the positive roles of dogs on human health. The research team received the approval and support of the Naskapi community of KWW, the community of MLJ, and the town of SCH, as part of the global project.