Emergency response using oral rabies vaccination of dogs -field data from Namibia demonstrate high efficiency.

Dog-mediated rabies is responsible for tens of thousands of human deaths annually, and in resource-constrained settings, vaccinating dogs to control the disease at source remains challenging for various reasons. Currently, rabies elimination efforts rely on mass dog vaccination by the parenteral route. While oral rabies vaccination (ORV) of dogs is primarily considered a tool to increase herd immunity, particularly by targeting free-roaming and stray dogs, here, we are showcasing an ORV-only approach as an emergency response model. Using a third-generation vaccine and a standardized egg-flavored bait, we assessed the effectiveness and vaccination under field conditions in the Zambezi region of Namibia. During this trial, with four teams and within four working days, 3097 dogs were offered a bait, of which 88,0% were considered vaccinated. Teams managed to vaccinate, on average, over 20 dogs/h, despite using a door-to-door vaccination approach. The favorable results both in terms of bait acceptance and successful vaccination as well as field applicability and effectiveness further support the great potential of ORV in dog rabies control programmes.

From Field Tests to Molecular Tools-Evaluating Diagnostic Tests to Improve Rabies Surveillance in Namibia.

Rabies is endemic in Namibia and is present both in wildlife carnivores and domestic free-roaming dogs. The disease thus represents a challenge for public human and veterinary disease control. Namibia has implemented a national strategic plan to control rabies and the country's activities are supported by international organizations. To this end, rabies diagnosis at the Central Veterinary Laboratory (CVL) was improved in the frame of a World Organization for Animal Health (WOAH) laboratory twinning program: from practical sampling techniques and the use of lateral flow devices to a novel universal and discriminatory quantitative real-time Reverse transcription polymerase chain reaction (RT-qPCR), which easily identify dog-associated rabies viruses. The procedures applied and the results can be used as a template to improve rabies laboratory diagnosis.

Investigation of the outbreaks of abortions and orchitis in livestock in Namibia during 2016-2018.

This study investigated outbreaks of seemingly related abortions and orchitis which occurred in the Khomas, Omaheke and Otjozondjupa regions of Namibia from 2016 to 2018, affecting cattle, sheep and goats. Fifty-nine questionnaires were administered, and 48 were completed giving an 81.4% return. The outbreaks were limited to Namibia's east and central regions, mainly on farms rearing cattle, sheep and goats and on farms with a mixture of these species. There was no significant difference between Khomas and other regions on abortion reporting at the farm level [X2 (1, N = 48) = 0.0002, p = 0.987851]. However, there was a significant difference in the abortions at the animal level among the three regions [X2 (2, N = 6246) = 239.8339, p = .00001]. In addition, the proportions of abortions calculated at the animal level at each farm were significantly different when the Khomas region was compared to the other regions. Seventeen cattle sera, 35 sheep sera, 52 caprine sera, 18 bovine liver samples, one caprine liver, five aborted cattle foetuses, two cattle placentas, 18 testes (one bull, eight bucks and nine rams) and ten bull sheath scrapings were collected and tested. Histopathology, microbiology, serology, immunohistochemistry, real-time PCR and mineral analytical techniques were used to establish the aetiology of the abortion and orchitis outbreaks. The gross and histopathological findings on the 18 testicles were characteristic of chronic orchitis. In aborted foetuses, significant histopathological findings included meconium aspiration, funisitis and cardiomyopathy. Placentitis and endometritis were the primary pathologies observed in cows. The bacteria isolated from microbiological samples included Enterococcus spp. (65.5% [19/29]), Enterobacter spp. (6.9% [2/29]) and Streptococcus spp. (10.3% [3/29]), Trueperella pyogenes (3.4% [1/29]), Stenotrophomonas maltophilia (3.4% [1/29]), Staphylococcus epidermidis (3.4% [1/29]), Providencia rettgeri (3.4% [1/29]) and Acinetobacter lwoffii (3.4% [1/29]), mostly opportunistic bacteria. On mineral analysis, 28%, 33%, 83%, 33% and 17% (n = 18) of cattle livers were low in copper, zinc, manganese, selenium and iron, respectively. Twenty-three percent (12/52) of the caprine sera were positive for Brucella melitensis on the Rose Bengal and complement fixation tests. Thirty-five ovine sera were tested for B. melitensis, B. ovis and Coxiella burnetii, and the prevalence for each was 2.9% (1/35). PCR tests on foetuses were all negative for Brucella spp., Coxiella burnetii, Chlamydia spp., Listeria monocytogenes, Salmonella spp., Campylobacter fetus spp., Leptospira pathogenic strains, bovine viral diarrhoea virus, Rift Valley fever virus, Anaplasma phagocytophilum and bovine herpes virus 4 Campylobacter fetus spp. and Trichomonas foetus spp. The authors concluded that Brucella spp., Enterococcus spp., Escherichia coli, Streptococcus spp., Trueperella pyogenes and Coxiella burnetii could have contributed to this outbreak. Micronutrient imbalances and pathogenic abiotic nanoparticles were also identified as possible contributors to the abortion outbreaks.

Oral rabies vaccination of dogs-Experiences from a field trial in Namibia.

Dog-mediated rabies is responsible for tens of thousands of human deaths annually, and in resource-constrained settings, vaccinating dogs to control the disease at source remains challenging. Currently, rabies elimination efforts rely on mass dog vaccination by the parenteral route. To increase the herd immunity, free-roaming and stray dogs need to be specifically addressed in the vaccination campaigns, with oral rabies vaccination (ORV) of dogs being a possible solution. Using a third-generation vaccine and a standardized egg-flavoured bait, bait uptake and vaccination was assessed under field conditions in Namibia. During this trial, both veterinary staff as well as dog owners expressed their appreciation to this approach of vaccination. Of 1,115 dogs offered a bait, 90% (n = 1,006, 95%CI:91-94) consumed the bait and 72.9% (n = 813, 95%CI:70.2-75.4) of dogs were assessed as being vaccinated by direct observation, while for 11.7% (n = 130, 95%CI:9.9-17.7) the status was recorded as "unkown" and 15.4% (n = 172, 95%CI: 13.4-17.7) were considered as being not vaccinated. Smaller dogs and dogs offered a bait with multiple other dogs had significantly higher vaccination rates, while other factors, e.g. sex, confinement status and time had no influence. The favorable results of this first large-scale field trial further support the strategic integration of ORV into dog rabies control programmes. Given the acceptance of the egg-flavored bait under various settings worldwide, ORV of dogs could become a game-changer in countries, where control strategies using parenteral vaccination alone failed to reach sufficient vaccination coverage in the dog population.

Rabies in kudu: Revisited.

Rabies infects all mammals; however, transmission cycles are only maintained in certain bat and carnivore species. The high incidence of rabies in Greater Kudu (Tragelaphus strepsiceros) observed in Namibia for over 40 years has led to postulation that independent virus transmission is occurring within this antelope population. We have analysed extensive experimental, epidemiological, phylogeographic and deep sequence data, which collectively refute maintenance of an independent rabies cycle in kudu. As rabies in kudu continues to have a negative impact on the Namibian agricultural sector, measures to protect kudu have been investigated, including the use of a third-generation oral rabies vaccine. Initial results show protection of kudu from rabies infection via the oral route, with an appropriate bait design, different application schedules and vaccination doses further enhancing the immune response. Rabies in kudu is a complex interplay at the wildlife-livestock interface and requires a concerted approach to successfully control.

Fighting Dog-Mediated Rabies in Namibia-Implementation of a Rabies Elimination Program in the Northern Communal Areas.

The major part of the global burden of dog-mediated rabies falls on Africa and Asia, where still an estimated 60,000 people die of the disease annually. Like in many African countries, dog-mediated rabies is a major public health concern in Namibia, costing the country an estimated 242 human deaths during the past two decades, in particular in the Northern Communal Areas (NCAs). Consequently, under the "One Health" concept, the Namibian government adopted a National Rabies Control Strategy in 2015, which strives to contribute to the global goal of ending dog-mediated human rabies deaths by 2030. A key component of this strategy was the implementation a dog rabies elimination program in the NCAs in 2016, being designed as a stepwise regional rollout strategy by building on experience gained in a pilot project area. The area of implementation covers approximately 263,376 km2 and 64 constituencies, with around 1.2 million inhabitants and estimated 93,000 dogs.

Investigation of infectious laryngotracheitis outbreaks in Namibia in 2018.

Between July and August 2018, two outbreaks of infectious laryngotracheitis caused the death of over 116,000 commercial poultry (layers and broilers) near the city of Windhoek, Namibia. A third outbreak occurred in September 2018 in the north of the country approximately 800 km from the original outbreaks. Sample collection and molecular epidemiological analyses revealed that the outbreaks were most likely caused by poor vaccination practices leading to the reversion to virulence of an ILT vaccine strain. The analyses also indicate that inaccurate declarations were made by one of the farms involved and that illegal movement of animals most likely occurred.

Ecology and epidemiology of rabies in humans, domestic animals and wildlife in Namibia, 2011-2017.

Rabies is a fatal zoonotic disease that causes a heavy burden on societies. Namibia, a country in southern Africa, is aiming at controlling the disease in its main reservoir, the domestic dog. To facilitate the implementation comprehensive information on the ecology and epidemiology of the disease and surveillance is of utmost importance. The study presented assesses the baseline data for both human and animal rabies surveillance in Namibia in recent times and establishes correlations with ecological and socio-economic data in order to provide an up-to-date picture on the epidemiology of rabies in Namibia. For instance, it was important to identify the main drivers in the epidemiology, and whether the control strategy by mass vaccination of dogs is undermined by cycles of rabies in wildlife. Rabies in humans was reported mainly from the Northern Communal Areas (NCAs), with a total of 113 cases from 2011 to 2017, representing an incidence of between 1.0 and 2.4 annual human rabies deaths per 100,000 inhabitants. Kavango, the region with the highest human rabies incidence was also the region with the lowest animal rabies surveillance intensity. Generally, the vast majority (77%) of dog samples originated from communal farm land, followed by urban areas (17%), while only a small fraction (3%) was submitted from freehold farm areas. In contrast, kudu and eland submissions were almost exclusively from freehold farmland (76%) and urban areas (19%), whereas the submission of cattle samples was evenly distributed among freehold farms (46%) and communal farm land (46%). The likelihood of sample submission decreased exponentially with distance to one of the two laboratories. Overall, 67% (N = 1,907) of all samples submitted tested rabies-positive, with the highest positivity rate observed in kudus (89%) and jackals (87%). The transmission cycle of rabies in dogs appears restricted to the northern communal areas of Namibia, whilst rabies in wildlife species is predominately reported from farmland in central Namibia, mostly affecting kudu (Tragelaphus strepsiceros) and livestock with a likely reservoir in wildlife canids such as jackals or bat-eared foxes. The analysis confirms the presence of two independent transmission cycles in Namibia with little geographic overlap, thus allowing for a sustainable control of rabies in dogs in the NCAs.

Experimental screening studies on rabies virus transmission and oral rabies vaccination of the Greater Kudu (Tragelaphus strepsiceros).

Rabies in the Greater Kudu (Tragelaphus strepsiceros) in Namibia is unique and found in such magnitude as has not been reported elsewhere in southern Africa. Reasons as to why Kudus appear to be exceptionally susceptible to rabies still remain speculative at best. Because the current severe rabies endemic in Kudus continues to have an enormous negative impact on the Namibian agricultural sector, we set out to question existing dogmas regarding the epidemiology of the disease in a unique experimental setting. In addition, we explored effective measures to protect these antelopes. Although we were able to confirm high susceptibly of kudus for rabies and sporadic horizontal rabies virus transmission to contact animals, we contend that these observations cannot plausibly explain the rapid spread of the disease in Kudus over large territories. Since parenteral vaccination of free-roaming Kudus is virtually impossible, oral rabies vaccination using modified life virus vaccines with a high safety profile would be the ultimate solution to the problem. In a proof-of-concept study using a 3rd generation oral rabies virus vaccine construct (SPBN GASGAS) we found evidence that Kudus can be vaccinated by the oral route and protected against a subsequent rabies infection. In a second phase, more targeted studies need to be initiated by focusing on optimizing oral vaccine uptake and delivery.