Recent Research April 2017

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A round-up of recent research relevant to GARC’s mission. Also see the article Applied research “Towards Elimination of Dog Mediated Human Rabies"

 

Human Vaccination

Pre-exposure rabies prophylaxis: a systematic review. A review of literature and field data concludes that PrEP is safe and immunogenic, and can be co-administered with other vaccinations. Simpler regimens are effective and booster intervals could be extended up to 10 years. However, currently PrEP campaigns would not be cost-effective in most situations and PrEP should not distract from other rabies control efforts.

Injecting rabies immunoglobulin (RIG) into wounds only: A significant saving of lives and costly RIG. Under conditions where RIG was extremely scarce, available eRIG was used in 269 patients as an emergency response and only for local infiltration of severe bite wounds by suspected rabid dogs. This was followed by intra-dermal rabies vaccination. A subgroup of 26 patients later identified as severely bitten by laboratory confirmed rabid dogs were followed for more than one year and all were found to be alive.

Barriers to innovation in human rabies prophylaxis and treatment: A causal analysis of insights from key opinion leaders and literature. A literature review and 23 semi-structured interviews with key opinion leaders identified barriers to innovation in human rabies medication and their root causes. The results stress the existence of barriers beyond the limited return on investment and explain why innovation is lagging behind that for lower burden NTDs. A re-orientation is necessary to meet unmet societal and medical needs.

Safety, tolerability and efficacy of intradermal rabies immunization with DebioJect™. Trial comparing rabies vaccination by (i) intradermal route using DebioJect™ (IDJ) devices, (ii) intradermal route using standard (Mantoux) method with classical needles (IDS), and intramuscular route with classical needles (IM). All participants were effectively immunized and no serious adverse events were recorded. The DebioJect™ device requires very little training to use and reliably delivers vaccine into the dermis. Significant decreases of pain at needle insertion and at vaccine injection were reported with IDJ compared to IDS and IM.

Knowledge, attitudes and practices regarding rabies risk in community members and healthcare professionals: Pétionville, Haiti, 2013. A knowledge, attitudes and practices survey of 550 community members and 116 health professionals in Pétionville, Haiti assessed the perception of rabies in these populations. Despite awareness of rabies in dogs and transmission routes, only 37% of participants sought medical treatment, and only 38% of respondents had vaccinated their dogs. Fewer than 15% of healthcare professionals had ever received training on rabies prevention and 77% did not know where to procure rabies vaccine for bite victims.

Advocacy

Vision 2030: Dog-mediated human rabies-free India: Action must begin now. At the 18th national conference of rabies organized by Association for Prevention and Control of Rabies in India (APCRI), it was resolved to support and work towards the global goal by ensuring a dog-mediated human rabies-free India by 2030. The conference called for a reassessment of the burden of rabies in India, for rabies to be made a notifiable disease, and a relaunching of the National Rabies Control Programme incorporating a clear one health action plan, road map, and task force.

Rabies: Still a silent killer targeting the poor. Commentary suggesting achieving the 2030 global goal is far from certain and that efforts to expand access to human PEP are still badly needed. Such efforts have reduced the human rabies cases in Thailand to less than 10 during the last decade.

Rationale and support for a One Health program for canine vaccination as the most cost-effective means of controlling zoonotic rabies in endemic settings. A review of data concludes that widespread dog vaccination is now warranted. PEP is effective in preventing human deaths, but is comparatively expensive and has little impact on the canine reservoir. Indiscriminate culling of the dog population is expensive and generally ineffective. Case studies illustrate how mass canine rabies vaccination has effectively reduced both canine and human rabies to minimal levels and can decrease the rabies economic burden by reducing expenditures on PEP.

Mass Dog Vaccination

Barriers to dog rabies vaccination during an urban rabies outbreak: Qualitative findings from Arequipa, Peru. Canine rabies was reintroduced to the city of Arequipa, Peru in March 2015. Despite mass dog vaccination campaigns, transmission continues in this complex urban environment, due to low dog vaccination coverage. Focus group discussions identified the reasons for this will help design better campaigns. Participants described low awareness about rabies and vaccination campaigns, mistrust of the campaign, being unable to handle their dogs, and low vaccination point accessibility in peri-urban areas.

Lyssaviruses and rabies: current conundrums, concerns, contradictions and controversies. Review that summarises progress in rabies control to date, and suggests ways forward. These include a more harmonized approach to viral taxonomy, enhanced de-centralized laboratory-based surveillance, focal pathogen discovery and characterization, applied pathobiological research for therapeutics, improved estimates of canine populations at risk, actual production of required vaccines and related biologics, strategies to maximize prevention but minimize unnecessary human prophylaxis, and a long-term, realistic plan for sustained global program support to achieve disease elimination.

Epidemiology

The history of rabies in the Western Hemisphere.  and Successful strategies implemented towards the elimination of canine rabies in the Western Hemisphere. A complementary pair of reviews. The first compiles historical and phylogenetic evidence of the origins and subsequent dynamics of rabies in the Western Hemisphere, from prior to the arrival of the first European colonizers to the present day, including host shifts to wildlife reservoirs.  The second analyses the successes and challenges of control attempts, including the impact of societal attitudes, economic disparity, and the threats from hotspots of remaining infection and dog-derived RABLV lineages. Complete elimination of canine rabies requires permanent funding, with governments and people committed to make it a reality.

One Health strategies for rabies control in rural areas of China. An opinion piece that argues rabies is a re-emerging disease in China, and that more focus on provision of PEP is needed. Virus strains derived from wildlife reservoirs are a threat and a greater understanding of rabies in wildlife and stray dogs is needed to improve control strategies.

Diagnosis

An inter- laboratory proficiency testing exercise for rabies diagnosis in Latin America and the Caribbean. Despite DFA being a critical capacity in the control of rabies, there is not a standardized protocol in the region. The first inter-laboratory proficiency exercise of national rabies laboratories in LAC countries indicated large variability in the laboratories throughput, equipment used, protocols availability, quality control standards and biosafety requirements.

Enhanced diagnosis of rabies and molecular evidence for the transboundary spread of the disease in Mozambique. Knowledge of the epidemiology of rabies in Mozambique is limited by sample submission, constrained diagnostic capabilities and a lack of molecular epidemiological research. The direct, rapid immunohistochemical test (DRIT) was tested as an alternative to the DFA. Of 29 rabies samples, 15 were DRIT-negative, which was confirmed by DFA and real-time PCR. The DRIT-positive results (14/29) were confirmed and sequenced. Phylogenetic analyses suggested that multiple instances of cross-border transmission may occur.