# TOWARDS ELIMINATION OF DOG MEDIATED HUMAN RABIES

EDITED BY: Salome Dürr, Anna Sophie Fahrion, Lea Knopf and Louise H. Taylor PUBLISHED IN: Frontiers in Veterinary Science & Frontiers in Public Health

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ISSN 1664-8714 ISBN 978-2-88945-299-6 DOI 10.3389/978-2-88945-299-6

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# **TOWARDS ELIMINATION OF DOG MEDIATED HUMAN RABIES**

### Topic Editors:

**Salome Dürr,** University of Bern, Switzerland **Anna Sophie Fahrion,** World Health Organization, Switzerland **Lea Knopf,** World Health Organization, Switzerland **Louise H. Taylor,** Global Alliance for Rabies Control, United States

An owner has his dog vaccinated during a mass dog vaccination campaign in the neighbourhood of Payatas in Manila, Philippines.

©2016 Geloy Conception and Global Alliance for Rabies Control

Rabies is an ancient zoonotic viral disease that still exerts a high impact on human and animal health. The disease is almost 100% fatal after clinical signs appear, and it kills tens of thousands of people per year worldwide, particularly in Africa and many parts of Asia. Although the disease in humans can be prevented by timely post-exposure prophylaxis, its access and affordability is limited in rabies endemic countries. With 99% of infections in humans caused by rabid domestic dog bites, controlling the infection in this reservoir population has been proven to be most effective to reduce and eliminate human rabies cases. In this context, this Research Topic invited contributions on the control and elimination of dog mediated human rabies. Publications on epidemiological, educational, policy-related and economic aspects of dog and human rabies surveillance, implementation of control in dogs and humans and scientific documentation of success stories were consolidated. We hope that these articles contribute to reaching the ambitious goal, set by key players in global health, of the elimination of dog mediated human rabies by 2030.

**Citation:** Dürr, S., Fahrion, A. S., Knopf, L., Taylor, L. H., eds. (2017). Towards Elimination of Dog Mediated Human Rabies. Lausanne: Frontiers Media. doi: 10.3389/978-2-88945-299-6

# Table of Contents

## *05 Editorial: Towards Elimination of Dog Mediated Human Rabies* Salome Dürr, Anna S. Fahrion, Lea Knopf and Louise H. Taylor

### **Identification of Challenges and Solutions:**

*07 The Road to Dog Rabies Control and Elimination—What Keeps Us from Moving Faster?*

Anna S. Fahrion, Louise H. Taylor, Gregorio Torres, Thomas Müller, Salome Dürr, Lea Knopf, Katinka de Balogh, Louis H. Nel, Mary Joy Gordoncillo and Bernadette Abela-Ridder

### **Evidence and Challenges of Rabies Elimination:**

*15 Tribulations of the Last Mile: Sides from a Regional Program*

Victor J. Del Rio Vilas, Mary J. Freire de Carvalho, Marco A. N. Vigilato, Felipe Rocha, Alexandra Vokaty, Julio A. Pompei, Baldomero Molina Flores, Natael Fenelon and Ottorino Cosivi

*20 Eliminating Dog-Mediated Rabies in Sikkim, India: A 10-Year Pathway to Success for the SARAH Program*

Helen Byrnes, Andrea Britton and Thinlay Bhutia

*26 A Century Spent Combating Rabies in Morocco (1911–2015): How Much Longer?*

Sami Darkaoui, Florence Cliquet, Marine Wasniewski, Emmanuelle Robardet, Nadia Aboulfidaa, Mohammed Bouslikhane and Ouafaa Fassi-Fihri

### *42 Toward Elimination of Dog-Mediated Human Rabies: Experiences from Implementing a Large-scale Demonstration Project in Southern Tanzania*

Emmanuel Abraham Mpolya, Tiziana Lembo, Kennedy Lushasi, Rebecca Mancy, Eberhard M. Mbunda, Selemani Makungu, Matthew Maziku, Lwitiko Sikana, Gurdeep Jaswant, Sunny Townsend, François-Xavier Meslin, Bernadette Abela-Ridder, Chanasa Ngeleja, Joel Changalucha, Zacharia Mtema, Maganga Sambo, Geofrey Mchau, Kristyna Rysava, Alphoncina Nanai, Rudovick Kazwala, Sarah Cleaveland and Katie Hampson

*52 The Ilocos Norte Communities against Rabies Exposure Elimination Project in the Philippines: Epidemiological and Economic Aspects*

Loida M. Valenzuela, Sarah I. Jayme, Anna Charinna B. Amparo, Louise H. Taylor, Maria Pinky Z. Dela Cruz, Dianne A. Licuan, Rosebelle Gamal-Bitao and Louis H. Nel

### **Improvement of Surveillance:**

*63 Qualitative Research to Design Sustainable Community-Based Surveillance for Rabies in Northern Australia and Papua New Guinea*

Victoria J. Brookes, Emma Kennedy, Phillipa Dhagapan and Michael P. Ward

### *72 Addressing the Disconnect between the Estimated, Reported, and True Rabies Data: The Development of a Regional African Rabies Bulletin*

Terence P. Scott, Andre Coetzer, Anna S. Fahrion and Louis H. Nel

### **Vaccination and Dog Management Strategies:**

*78 Rabies Vaccination Targets for Stray Dog Populations* Tiffany Leung and Stephen A. Davis

### *88 Corrigendum: Determinants of Vaccination Coverage and Consequences for Rabies Control in Bali, Indonesia*

Riana A. Arief, Katie Hampson, Andri Jatikusumah, Maria D. W. Widyastuti, Sunandar, Chaerul Basri, Anak A. G. Putra, Iwan Willyanto, Agnes T. S. Estoepangestie, I. W. Mardiana, I. K. G. N. Kesuma, I. P. Sumantra, Paul F. Doherty Jr., M. D. Salman, Jeff Gilbert and Fred Unger

### *89 Comparing Methods of Assessing Dog Rabies Vaccination Coverage in Rural and Urban Communities in Tanzania*

Maganga Sambo, Paul C. D. Johnson, Karen Hotopp, Joel Changalucha, Sarah Cleaveland, Rudovick Kazwala, Tiziana Lembo, Ahmed Lugelo, Kennedy Lushasi, Mathew Maziku, Eberhard Mbunda, Zacharia Mtema, Lwitiko Sikana, Sunny E. Townsend and Katie Hampson

### *101 The Role of Dog Population Management in Rabies Elimination—A Review of Current Approaches and Future Opportunities*

Louise H. Taylor, Ryan M. Wallace, Deepashree Balaram, Joann M. Lindenmayer, Douglas C. Eckery, Beryl Mutonono-Watkiss, Ellie Parravani and Louis H. Nel

### **Cost-Effectiveness and Economic Considerations:**

### *116 Cost Description and Comparative Cost Efficiency of Post-Exposure Prophylaxis and Canine Mass Vaccination against Rabies in N'Djamena, Chad*

Rolande Mindekem, Monique Sarah Lechenne, Kemdongarti Service Naissengar, Assandi Oussiguéré, Bidjeh Kebkiba, Daugla Doumagoum Moto, Idriss Oumar Alfaroukh,Laurent Tinoanga Ouedraogo, Sahidou Salifou and Jakob Zinsstag

### *127 Elimination of Dog-Mediated Human Rabies Deaths by 2030: Needs Assessment and Alternatives for Progress Based on Dog Vaccination*

Ryan M. Wallace, Eduardo A. Undurraga, Jesse D. Blanton, Julie Cleaton and Richard Franka

## *141 Rabies Control: Could Innovative Financing Break the Deadlock?*

Susan C. Welburn, Paul G. Coleman and Jakob Zinsstag

# Editorial: Towards Elimination of Dog Mediated Human Rabies

#### *Salome Dürr1 \*, Anna S. Fahrion2 , Lea Knopf 2 and Louise H. Taylor3*

*1Veterinary Public Health Institute, University of Bern, Bern, Switzerland, 2Neglected Zoonotic Diseases, Department of Control of Neglected Tropical Diseases, World Health Organization, Geneva, Switzerland, 3 Global Alliance for Rabies Control, Manhattan, KS, United States*

Keywords: rabies, elimination, global health, resources, vaccination, dogs, one health, zoonosis

### **Editorial on the Research Topic**

### **Towards Elimination of Dog Mediated Human Rabies**

Rabies is a zoonotic viral disease with a high impact on human and animal health. The disease is almost 100% fatal after clinical signs appear and kills tens of thousands of people per year worldwide. About 99% of infections in humans are caused by rabid domestic dog bites. Human disease is related to poverty, with the highest burden in Asian and African low-income settings. Along with the group of neglected tropical diseases, increasingly recognized by high-level global health policy as indicators of functionality of health systems, rabies is scheduled for potential elimination as part of the UN sustainable development goals. In late 2015, the international rabies community, represented by more than 100 (mostly rabies endemic) countries, set a global target of eliminating human rabies mediated by dogs by 2030. Despite this momentum, rabies has received relatively less international attention compared with some of the other NTDs as of yet.

### *Edited by:*

*Andres M. Perez, University of Minnesota, United States*

#### *Reviewed by:*

*Flavie Luce Goutard, Agricultural Research Centre for International Development, France*

*\*Correspondence:*

*Salome Dürr<EMAIL_ADDRESS>
#### *Specialty section:*

*This article was submitted to Veterinary Epidemiology and Economics, a section of the journal Frontiers in Veterinary Science*

*Received: 21 June 2017 Accepted: 14 August 2017 Published: 31 August 2017*

#### *Citation:*

*Dürr S, Fahrion AS, Knopf L and Taylor LH (2017) Editorial: Towards Elimination of Dog Mediated Human Rabies. Front. Vet. Sci. 4:142. doi: 10.3389/fvets.2017.00142*

In this research topic, 123 authors contributed 15 articles (9 original research articles, 4 perspective pieces, and 2 reviews) from different regions in the world (4 from Australasia, 5 from Africa, 1 from Latin America, 4 global, and 1 theoretical) discussing various aspects of working towards the achievement of this goal. The collection brings together the experience and lessons learned from rabies control programs small and large, research aimed at improving the design and cost-effectiveness of rabies control programs, and analysis of the resources needed to expand rabies control efforts.

Our understanding of rabies control is sufficient, and the key tools are available to eliminate the disease. However, an overview by Fahrion et al. highlights the challenges and barriers to successfully *implementing* sustainable control of the disease. This article sets the scene for the whole collection, by discussing not just the gaps but also possible solutions for the socio-political, organizational, technical, and resource-linked issues that are being addressed by many different stakeholders. It highlights the need for applied research, a feature that has been taken up by most of the articles of this research topic.

Evidence that rabies can be locally eliminated has been built in recent years in a variety of settings, demonstrated here by Byrnes et al., Valenzuela et al., and Mpolya et al., describing successful statewide programmes in Sikkim, India, Ilocos Norte, Philippines, and Southeast Tanzania and Pemba Island. All the programs were implemented by the government, in collaboration with one or more organizations, such as NGOs, WHO, OIE, national and international research institutes, and private foundations. Mass rabies vaccination in dogs and promotion of post-exposure prophylaxis (PEP) in humans were the common interventions, supported by dog population management (Byrnes et al.) and promotion of surveillance (Valenzuela et al.; Mpolya et al.), including the use of innovative methods such as mobile phone tools (Mpolya et al.), and the transition to intradermal PEP delivery (Mpolya et al.). Two facts were highlighted in all case studies, namely, the importance of a One Health approach demanding involvement of stakeholders from the veterinary and public health sectors and the challenge of sustaining progress in areas situated amidst rabies endemic areas.

From all projects there are lessons to be learned that can be used to support efforts elsewhere. This is particularly true for the coordinated approach to rabies control programs across Latin America and Caribbean (LAC), described by Del Rio Vilas et al., whose lessons derived are highly relevant to large-scale regional elimination goals. Although the target to eliminate rabies from LAC had to be reset four times since the implementation of the program in 1983 (it is currently set to 2022), a massive reduction of the human and animal rabies cases to (almost) 0 in most of the LAC countries has been achieved. One of the key messages is the need for adapted regional and national strategies to recognize that countries can vary enormously in their capacities.

Long-term intensive programs are required to achieve sustainable elimination and ensure that the reduction of cases is not followed by a resurgence of the incidence. The example from Morocco described by Darkaoui et al. demonstrates how inadequate implementation of the law, slack requests for responsibility from dog owners, and weak collaboration between Ministries impeded success in controlling rabies. Arief et al. also highlight the need for sustained control efforts in Bali, Indonesia, where dramatic reduction of rabies cases were achieved, but resurgence of disease has shown that elimination was still not possible.

What are the knowledge and action gaps that need to be addressed to implement sustainable rabies control programs at small and large scales? Concrete examples are addressed in articles of this research topic:

**Conflict of Interest Statement:** The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

*Copyright © 2017 Dürr, Fahrion, Knopf and Taylor. This is an open-access article distributed under the terms of the Creative Commons Attribution License*  safe, effective, cheap, and injectable contraceptives for females should be a research priority to benefit management of dog populations.

It is noteworthy that almost all contributions highlighted the need for an intersectoral approach involving all stakeholders, including the engagement of the communities. A One Health approach along the path to disease elimination (from resource allocation, to raising awareness, surveillance, implementation of control interventions, and eventual elimination) is a crucial requirement to realize the goal of 2030. To borrow words from Wallace et al., this research topic "hopes to stimulate and inform the necessary discussion on global and regional strategic planning, resource mobilization, and continuous execution of rabies virus elimination" that will be necessary to eliminate humanmediated canine rabies by 2030—a target that should not be reset.

## AUTHOR CONTRIBUTIONS

All the authors were involved in writing the article and in editing contributions to this research topic. They all agree to the final version of this article.

*(CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.*

# The Road to Dog Rabies Control and Elimination—What Keeps Us from Moving Faster?

*Anna S. Fahrion1 \*, Louise H. Taylor 2 , Gregorio Torres 3 , Thomas Müller 4 , Salome Dürr 5 , Lea Knopf 1 , Katinka de Balogh6 , Louis H. Nel 2,7 , Mary Joy Gordoncillo3 and Bernadette Abela-Ridder 1*

*1Neglected Zoonotic Diseases, Department of Control of Neglected Tropical Diseases, World Health Organization, Geneva, Switzerland, 2Global Alliance for Rabies Control, Manhattan, KS, USA, 3World Organisation for Animal Health, Paris, France, 4 Institute of Epidemiology, Friedrich-Löffler-Institut, Federal Research Institute for Animal Health, Greifswald, Germany, 5Veterinary Public Health Institute, University of Bern, Bern, Switzerland, 6 Food and Agriculture Organization of the United Nations, Bangkok, Thailand, 7Department of Microbiology and Plant Pathology, Natural and Agricultural Sciences, University of Pretoria, Pretoria, South Africa*

#### *Edited by:*

*Leland Shapiro, University of Colorado at Denver, USA*

#### *Reviewed by:*

*Edward N. Janoff, University of Colorado at Denver, USA Ashley C. Banyard, Animal and Plant Health Agency, United Kingdom*

> *\*Correspondence: Anna S. Fahrion<EMAIL_ADDRESS>
#### *Specialty section:*

*This article was submitted to Infectious Diseases, a section of the journal Frontiers in Public Health*

*Received: 07 November 2016 Accepted: 18 April 2017 Published: 15 May 2017*

#### *Citation:*

*Fahrion AS, Taylor LH, Torres G, Müller T, Dürr S, Knopf L, de Balogh K, Nel LH, Gordoncillo MJ and Abela-Ridder B (2017) The Road to Dog Rabies Control and Elimination—What Keeps Us from Moving Faster? Front. Public Health 5:103. doi: 10.3389/fpubh.2017.00103*

Rabies, a vaccine preventable neglected tropical disease, still claims an estimated 35,000–60,000 human lives annually. The international community, with more than 100 endemic countries, has set a global target of 0 human deaths from dog-transmitted rabies by 2030. While it has been proven in several countries and regions that elimination of rabies as a public health problem is feasible and tools are available, rabies deaths globally have not yet been prevented effectively. While there has been extensive rabies research, specific areas of implementation for control and elimination have not been sufficiently addressed. This article highlights some of the commonest perceived barriers for countries to implementing rabies control and elimination programs and discusses possible solutions for sociopolitical, organizational, technical, and resource-linked requirements, following the pillars of the global framework for the elimination of dogmediated human rabies adopted at the global rabies meeting in December 2015.

Keywords: rabies, dog rabies, neglected tropical diseases, zero human deaths, global framework, implementation

### BACKGROUND

During the past decade, neglected tropical diseases (NTDs) have gained more recognition on the global health and development agendas (1–3). The transition from the Millennium Development Goals to the Sustainable Development Goals has renewed emphasis on ending the inequality that has deprived neglected communities from access to effective and affordable health care (Goal 3.8) and includes a specific goal to end NTDs by 2030 (Goal 3.3) (4).

Rabies, a viral disease categorized by the World Health Organization (WHO) as a NTD, kills tens of thousands of people every year, mostly among underserved populations in Africa and Asia; more than 95% of human rabies deaths result from the bites of infected dogs (5, 6). While the disease is almost 100% fatal, effective human and dog vaccines to prevent rabies are available. Elimination of dog-transmitted rabies as a public health problem is feasible (7, 8) by vaccinating dogs and providing post-exposure prophylaxis (PEP) to humans until dog rabies is eliminated (5).

Elimination of canine rabies is integral to the WHO–OIE1 – FAO2 tripartite collaboration, which works at the animal–human– ecosystems interface (9, 10). A joint global meeting (Geneva, December 2015) marked a milestone at which human and animal health sectors agreed a framework to eliminate canine rabies with the vision of ending dog-mediated human rabies by 2030 (8) (**Figure 1**). All 180 Member countries of the OIE affirmed this commitment in Resolution N.26 adopted by the World Assembly of Delegates of the OIE in May 2016.3

Rabies is widely recognized as a public health threat that warrants prioritization of control efforts in Asia (11–13), Africa (14), and among the least developed nations globally (15). Health leaders are increasingly aware that this fatal disease could be eliminated as a public health problem cost effectively in a relatively short time (7, 16), yet rabies remains neglected and progress remains slow.

While there has been extensive research on the rabies virus, a comparative lack of operational research has led to knowledge gaps in how to design and implement control and elimination programs where they are needed most (11, 17) and calls for a "science of rabies elimination" (18). What barriers remain to coordinated efforts within and among countries? What is needed to transform the increased public and political awareness into real progress on the ground? And ultimately, what is needed to translate existing knowledge into success against rabies in a country? This paper discusses aspects of the "science to policy gap," (perceived) barriers to progress and possible solutions (**Table 1**). It is structured according to the pillars of the Global framework for the elimination of dog-mediated human rabies (**Figure 1**), namely, sociocultural, technical, organization, political, and resources, reflecting a coordinated approach.

### OVERCOMING BARRIERS TO RABIES ELIMINATION

### Political or Sociocultural—Raising Public Awareness and Political Will

#### Making the Burden Visible, Demonstrating Impact

Prioritization of a disease is brought about through increasing public awareness and political will (19). One of the most important

1World Organization for Animal Health.

2Food and Agriculture Organization of the United Nations.

3http://www.oie.int/fileadmin/Home/eng/About\_us/docs/pdf/Session/2016/A\_ RESO\_2016\_public.pdf.

TABLE 1 | Key areas for improvement, necessary actions, and the stakeholders required to take action to support programmatic success for canine rabies elimination.

*a "International organizations" refers primarily to the FAO/OIE/WHO tripartite and global NGOs such as Global Alliance for Rabies Control (GARC). But these roles and principles are equally valid for other organizations working in rabies or zoonosis control.*

*bA WHO Strategic Advisory Group of Experts on Immunization (SAGE) working group on rabies vaccines and rabies immunoglobulins was established in 2016 and is currently reviewing the scientific evidence and relevant programmatic considerations on the use and scheduling of these. The proposed recommendations resulting from this work will be considered by SAGE during its October 2017 meeting.*

means of convincing policy makers to prioritize a disease and invest resources is to demonstrate its impact on public health and the economy and the potential benefit of targeting the disease.

High-quality surveillance data are needed, but human rabies deaths are commonly underreported 100-fold (20–22), and the absence of data and solid evidence for estimates induces a cycle of neglect (23). Conversely, the onset of a control program that delivers better surveillance data is a precondition to increased awareness. Where quantitative assessments have been attempted, rabies has been ranked consistently among the top five zoonotic diseases, for example, in India (12), Mongolia (13), Jordan (24), Ethiopia (25), Myanmar (26), and Kenya (27).

Declaring a disease notifiable is crucial to establish functional reporting (28), and monitoring and surveillance of the disease should, therefore, be a central element of every rabies program. Rabies is also included in the OIE list of notifiable diseases.4 Disease surveillance starts at the community level, where awareness about the disease needs to be complemented by clear guidance on reporting to the authorities, ideally integrated into the wider national health information and statistics systems. Pathways

4 http://www.oie.int/en/international-standard-setting/terrestrial-code/ access-online/.

must be included for transmission of data from the community level to the national level and to the OIE and WHO, resulting in feedback and action to keep individuals along the reporting chain informed and engaged. To ensure that data are comparable and informative, indicators should be well-defined and measurable. Novel technology such as notification *via* cell phones could be further explored (29).

### Creating Public Awareness

Rabies burdens individuals, families, societies, and economies (6). As communities become aware of this threat, political pressure to act will accumulate. Building awareness and education about how to avoid and treat rabies exposures is, therefore, crucial in mobilizing a country to eliminate rabies. Champions at all levels (community to national) are central to this effort as they directly advocate and educate communities (7). World Rabies Day, recognized by the United Nations and commemorated every year on 28th September, celebrated its 10th anniversary in 2016 with 302 events in 57 countries (as of December 21, 2016). This annual awareness-raising event has shown a remarkable upwards trend since its inception and is an example of the dedication of innumerable people worldwide (30, 31).

### Building an Engaged Society

An integral part of a regional or national plan is to build a proactive society that is fully engaged in the dog rabies elimination efforts of the country. Awareness of rabies at the community level alone is not enough to increase pressure on governments to improve their control efforts. Besides well-informed general public and responsible pet owners, committed, supportive policy makers are needed who will cohesively support national efforts to achieve and maintain freedom from rabies. Currently, most efforts to raise public awareness focus on promoting rabies information, which may not translate into the desired behavior, practices, and actions. Thus, it is important to invest in a national communication strategy and in impact monitoring that use the science of behavioral change and consider the diverse behavioral drivers, incentives, motivations, and larger sociocultural context of the target audience.

An example of behavioral change necessary for rabies control is that owners accept responsibility for their dogs and any offspring they may produce. This includes protecting dogs from rabies through vaccination and from unwanted reproduction. The promotion of such responsible dog ownership can be achieved only through a combination of adequate legislation, public awareness, and education, recognizing cultural and economic conditions. Public health and veterinary authorities, animal welfare organizations, and private veterinarians should work together to establish and maintain responsible dog ownership programs especially in communities at risk.

### Organizational—Establishing Necessary Policies and Guidance

### Effective Planning of Elimination Programs

National authorities are responsible for developing national strategies and implementing programs but they are frequently overwhelmed by multiple human and animal disease priorities and the challenges associated with programs stretched across sectors and administrative levels. It may be difficult to know where to start and what is needed—a potential barrier. Guidance for developing and monitoring control and elimination programs is, however, freely available. For example, the Stepwise Approach toward Rabies Elimination, which is embedded in the rabies blueprint,5 follows the principles of enhancing intersectoral collaboration. This guidance has been used by countries across three continents, mostly at national or regional stakeholder consultations, to kick-start coordinated rabies control (32). Likewise, the rabies surveillance blueprint6 provides guidance for planning of surveillance in particular. Knowledge about these tools needs to be disseminated and promoted more widely.

### Intersectoral Collaboration

While the incremental benefits of a One Health approach for rabies control are established at the highest international level, its operationalization at national or local levels remains a challenge. Administrative and management structures may need to be harmonized across sectors according to different ministries and budget lines and coordinated with stakeholders from the private sector (33). National stakeholder consultations that convene all actors across ministries, local and national levels as well as the private and public sectors, however, have proven excellent platforms from which to build connections and trust and from where operational barriers and constraints to effective collaboration in rabies prevention as well as possible solutions can be explored. The outcome of these consultations is the drafting of integrated, multidisciplinary rabies action plans (34). For example, coordination at the national level can pave the way for integrated management of bite cases at the local level, jointly involving human and animal professionals to ensure reporting of bite and rabies incidents, proper risk assessments, and a coordinated response while at the same time sharing logistic resources (35, 36). Close involvement of social sciences, the education sector, and municipalities is now equally recognized, for example, as a powerful method for preventing dog bites in children, increasing knowledge and awareness about rabies, and in sustainably managing dog populations in affected communities (36).

### Sharing and Comparing: Transparency and Regional Collaboration

International cooperation and coordination in planning, implementing, and evaluating rabies control programs at all levels is crucial for success and cost effectiveness (5). As canine rabies is a transboundary disease, collaboration, cooperation, and transparency between countries can provide new insights for tackling the disease. Authorities often perceive admitting public health problems as failure and prefer not to address endemic rabies at international level, thereby missing an opportunity to share information. Establishing contacts between public health and veterinary authorities of neighboring regions and countries and

5http://caninerabiesblueprint.org/.

6http://rabiessurveillanceblueprint.org/.

frequently exchanging information and data can be a first step toward building trust and more regular bilateral or multilateral interaction. WHO collaborating centers, OIE, and FAO reference laboratories and other organizations can help countries to share, compare, and learn from each other's experience (5, 37). Participation at international disease conferences can also attract more international attention at a political level.

A regional approach has been fundamentally important for the effective control of rabies in Western Europe (5) and, more recently, Latin America (38). Rabies control program managers from across Latin America and the Caribbean meet at meetings facilitated by the Pan American Health Organization (REDIPRA) and the large scale, parallel declines in dog and human rabies achieved are striking (39). In Asia, the Association of Southeast Asian Nations launched a joint Rabies Elimination Strategy that encapsulates a regional approach in 2015.7 The Middle Eastern, Eastern Europe, Central Asia, and North Africa Rabies Experts Bureau has held meetings since 2010 (40) and has called for a strong regional initiative with high level political support (41). In sub-Saharan Africa, the Pan-African Rabies Control Network was created in 2015 and shows promise as a suitable platform to drive a regional approach to rabies control (37). Such regional approaches will be vital to implementing the global strategic framework to eliminate dog-mediated rabies and will, therefore, require further extension with strong participation and political support from all countries for success.

### Technical—Ensuring Necessary Technology and Knowledge Diagnostics

Diagnostic tests confirm animal rabies cases, allowing better PEP decision-making and monitoring the progress of control efforts. The reference, fluorescent antibody test, is not practicable in many endemic settings due to costs and enhanced laboratory requirements. Thus, alternative tools using less specialized equipment, such as Direct Rapid Immunohistochemical Test (42) and lateral flow devices (43), could play an important role provided further validation and quality approval.

### Predicting the Need for Vaccine: Forecasting

Manufacturing cycles of both human and animal rabies vaccines require several years of appropriate forecasting by countries in order to supply the actual need. An absence of accurate data impairs forecasting and thereby resource allocation. The veterinary services of endemic countries often have insufficient knowledge of dog population size or ecology and human health services lack accurate data on bite case exposures. Both sectors thus suffer from procurement delays or stock shortages, which can result in less effective control of the disease and may force countries to turn to manufacturers selling vaccines that are overly expensive or may not meet international quality standards (44). Vaccine banks or stockpiles at regional levels as managed by OIE or WHO have become a solid mechanism for countries to maintain the supply of quality-assured vaccines and allow manufacturers to forecast and stabilize their production over years with lowered pricing through bulk purchase (45). Moreover, vaccine banks have contributed demonstrably to the scaling up and maintenance of local, national, or sub-regional programs in Asia and Africa (46) and incentivized recipient countries to increase data collection, as reporting on vaccine use and results is required. The opportunity of a potential investment from GAVI (the Vaccine Alliance) into human rabies vaccine from 2018 onward (47) could substantially facilitate low-income countries' access to affordable rabies vaccine and stimulate the necessary political will to tackle human rabies at a large scale.

### Getting the Vaccines to the Community

Despite the encouraging improvements observed in the field of universal health coverage, poor accessibility to and affordability of PEP [particularly of rabies immunoglobulin (RIG)] remain in most rabies-endemic countries (48). Certainly, progress has been made, for example, on shortening PEP regimens (fewer health facility visits) and countries changing their policy to cost-saving intradermal administration of rabies vaccines as recommended by WHO (49). There is hope that new technologies currently under evaluation by WHO (thermostable rabies vaccine, monoclonal antibodies as an alternative to human and equine RIG) will facilitate cost-effective delivery of PEP as well as dog vaccine to where it is needed. The long needed scale up and adaption of mechanisms for supply and distribution of PEP has received a global push through discussions around a potential GAVI investment.

 Its control requires an adequate understanding of the dog ecology and dog-keeping practices in a country in locally differing sociocultural contexts (e.g., urban vs rural, among different economic, religious, or ethnic groups). Factors that can profoundly affect rabies transmission and control are usually not sufficiently understood to design the most appropriate control strategy, and as a result, efforts and resources can be wasted. In most circumstances, almost all dogs can be handled and vaccinated by the parenteral route (50). In rare cases, however, dogs may not be accessible to parenteral vaccination, thus jeopardizing the coverage of vaccination campaigns. Improved dog capture and vaccination techniques, as shown through the establishment of rabies A-teams by FAO in Bali, can assist with reaching dogs that are difficult to capture and handle.8 Oral dog vaccination using a hand-out model may be used effectively to immunize those inaccessible dogs while ensuring the safety of the vaccinators, the community, and non-target species. The best feasible solution for long-lasting marking of vaccinated dogs should be decided on during planning of campaigns (51).

The lack in dog movement control has been attributed as responsible for rabies spread in endemic areas and incursion in previously free countries or regions. Vaccinating at least 70% of

7http://vncdc.gov.vn/files/article\_attachment/2015/3/endorsed-ares-final.pdf.

8http://www.fao.org/indonesia/news/detail-events/en/c/411271/.

animals in order to eliminate rabies from a free-roaming dog population is a widely acknowledged recommendation (8). However, empirical work [e.g., on area-specific basic reproductive ratio (*R*0) (52)] suggests that different settings probably require different vaccination strategies and coverages to control rabies successfully. High vaccination coverage in high-risk areas may be more crucial than medium coverage across the whole country, but clear guidance on this is lacking. Better knowledge of area/ country specific factors related to dog-keeping practices, dog population turnover, and contact rates between dogs and wildlife can help in determining a more flexible, realistic required dog vaccination coverage. This can help to optimize resource allocation (53, 54) and define the most appropriate vaccination strategies and financing (55), the best vaccination campaign frequency (52), and how to target vaccination to the highest risk areas and segments of the dog population.

### Making Resources Available

As for any public health program, sustainable funding sources are a precondition to starting a rabies control program, and the absence of those sources is one of the main barriers. There are ways, however, to reduce the investments necessary for rabies control and to integrate rabies into existing streams of work and financing.

Recognizing rabies control as a public good and thus as the responsibility of national governments is key to a sustainable rabies elimination effort. Donor contributions should be structured so as to be catalytic to the establishment of the program, and long-term dependence on donor support should be avoided through a well-planned strategy for donor exit.

In most rabies-endemic countries, human PEP and vaccinating animals against rabies remain an "out-of-pocket" market. As they build on their commitments to universal health coverage and the sustainable development goals (56), governments need to step up their funding and integrate rabies control into sustainable health plans, ensuring dog vaccination, and PEP are available at the primary health-care level. Costs can be substantially decreased by using the intradermal route for human vaccines and tailoring dog vaccination to local circumstances (see above). Rabies surveillance and control in dogs should be integrated into existing infectious diseases reporting mechanisms and vaccination programs, requiring also more integration of funding streams. For example, in the Philippines, the ministry of health invests in dog vaccination as a public health measure, creating a leverage effect (57). Innovative mechanisms for financing and cost sharing can help to make vaccine purchase more affordable. To support funding bodies in planning and costing, WHO is currently developing in collaboration with FAO, OIE, and the Global Alliance for Rabies Control, a comprehensive business plan that

### REFERENCES

encompasses both human and animal perspectives for achieving the 2030 target. In the longer term, investing in rabies prevention and control is cost-efficient, saving both lives and money (16, 58). It is possible to start small and then unlock more investment by demonstrating value.

Capacity building is an investment in human resources with crucial importance for the sustainability of a project. Parallel to the technical efforts made by the country, plans to build related capacity through training, professional development, and/or continuing education will ensure quality at implementation and ensure future sustainability. This contribution to health systems' strengthening can be a legacy that rabies control efforts leave to a nation.

## CONCLUSION

This paper describes some of the main technical, organizational, and political challenges that countries encounter when implementing measures to control and eliminate rabies. However, there are solutions to many of these perceived barriers and opportunities to fill existing gaps. As summarized in **Table 1**, health officials, program managers, donors/investors, and all those involved in development of strategies should be aware of those applicable to their local, national, and regional contexts as early as possible, to make coordinated, informed decisions and successfully fight this devastating disease.

## AUTHOR CONTRIBUTIONS

BA-R, LT, and AF prepared the initial concept for this paper. All the authors contributed equally to the further development of the content, delivered specific paragraphs for the paper from their area of expertise, and reviewed and complemented the manuscript. AF coordinated and collated the coauthor's input.

## ACKNOWLEDGMENTS

The authors thank hundreds of tireless rabies fighters around the globe who do not cease to work hard for awareness, education, and vaccination and save lives by doing so. Dongwook Kim contributed significantly to the literature search for this article and the authors thank him for this contribution.

## FUNDING

All authors contributed to this article as a part of their professional mandate.

of dog-bite exposure in Karachi: prospective surveillance using a low-cost mobile phone system. *PLoS Negl Trop Dis* (2013) 7(12):e2574. doi:10.1371/ journal.pntd.0002574

*Foundation Project on Eliminating Human and Dog Rabies*. Geneva: World Health Organization (2015). Contract No.: WHO/HTM/NTD/NZD/2015.3.

58. Zinsstag J, Dürr S, Penny MA, Mindekem R, Roth F, Menendez Gonzalez S, et al. Transmission dynamics and economics of rabies control in dogs and humans in an African city. *Proc Natl Acad Sci U S A* (2009) 106(35): 14996–5001. doi:10.1073/pnas.0904740106

**Conflict of Interest Statement:** The authors declare an absence of any commercial or financial relationships to the content of the paper that could constitute a potential conflict of interest.

The reviewer ENJ and handling editor declared their shared affiliation, and the handling editor states that the process nevertheless met the standards of a fair and objective review.

*Copyright © 2017 Fahrion, Taylor, Torres, Müller, Dürr, Knopf, de Balogh, Nel, Gordoncillo and Abela-Ridder. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.*

# Tribulations of the Last Mile: Sides from a Regional Program

*Victor J. Del Rio Vilas1,2 \*, Mary J. Freire de Carvalho1 , Marco A. N. Vigilato1 , Felipe Rocha1 , Alexandra Vokaty1 , Julio A. Pompei1 , Baldomero Molina Flores1 , Natael Fenelon1 and Ottorino Cosivi1*

*1Pan American Foot-and-Mouth Disease Center (PANAFTOSA), Pan American Health Organization, Regional Office of the World Health Organization for the Americas (PAHO/WHO), Rio de Janeiro, Brazil, 2School of Veterinary Medicine, University of Surrey, Guildford, UK*

In Latin American and Caribbean (LAC) countries, the number of cases of dog-mediated human rabies is at its lowest since the onset of the Regional Program for Rabies Elimination in 1983, a commitment from LAC countries to eliminate dog-mediated rabies coordinated by the Pan American Health Organization. Despite minor setbacks, the decline in the number of human cases has been constant since 1983. While many LAC countries have significantly reduced rabies to a level where it is no longer significant public health concern, elimination has proven elusive and pockets of the disease remain across the region. In the 33-year period since 1983, the region has set and committed to four dates for elimination (1990, 2000, 2012, and 2015). In this paper, we ponder on the multiple causes behind the elusive goal of rabies elimination, such as blanket regional goals oblivious to the large heterogeneity in national rabies capacities. Looking ahead to the elimination of dog-mediated rabies in the region, now established for 2022, we also review the many challenges and questions that the region faces in the last mile of the epidemic. Given the advanced position of the Americas in the race toward elimination, our considerations could provide valuable knowledge to other regions pursuing elimination goals.

#### Keywords: rabies, canine mediated, America, regional program, elimination

## INTRODUCTION

In 1983, when dog-mediated rabies in the American region was the cause of over 200 human deaths and 12,000 dog cases per year, representatives from the countries, gathered at the first Regional Meeting of Rabies Program Directors (REDIPRA) (1) coordinated by the Pan American Health Organization (PAHO/WHO), had the vision of a future free of dog-mediated rabies. Armed with nerve tissue vaccine for dogs, they launched a region-wide plan leading to mass dog vaccination campaigns across the region and set up the first elimination goal for the Americas, by 1990. Three other elimination goals followed in 2000, 2012, and 2015. Although the goal was not achieved by 2015, the coordinated regional efforts toward elimination led to the control of dog-mediated rabies in most of the Americas. At the time of writing, eight dog-mediated human rabies cases have been reported across the region in 2016, all in Haiti.

In the following, we ponder on the possible reasons that may have contributed to the four missed elimination goals to date, and specifically target the final years of the regional control program. We then speculate on the main challenges that lay ahead. Our considerations, necessarily from a regional

#### *Edited by:*

*Lea Knopf, World Health Organization, Switzerland*

#### *Reviewed by:*

*Hans-Hermann Thulke, Helmholtz Centre for Environmental Research (UFZ), Germany Hsin-Yi Weng, Purdue University, USA*

#### *\*Correspondence:*

*Victor J. Del Rio Vilas<EMAIL_ADDRESS>
#### *Specialty section:*

*This article was submitted to Veterinary Epidemiology and Economics, a section of the journal Frontiers in Veterinary Science*

*Received: 17 November 2016 Accepted: 11 January 2017 Published: 31 January 2017*

#### *Citation:*

*Del Rio Vilas VJ, Freire de Carvalho MJ, Vigilato MAN, Rocha F, Vokaty A, Pompei JA, Molina Flores B, Fenelon N and Cosivi O (2017) Tribulations of the Last Mile: Sides from a Regional Program. Front. Vet. Sci. 4:4. doi: 10.3389/fvets.2017.00004*

perspective, are based on the experience of the region in the race toward elimination and could provide valuable knowledge to other regions pursuing similar goals.

### CHALLENGES PAST AND FUTURE

### On Program Management

At the announcement during the last REDIPRA meeting in 2015 (1) that the fourth elimination goal was not going to be achieved, PAHO and the countries did not establish another deadline, but agreed on a pathway toward the definition of the next goal. Two possible future goals were discussed: (i) elimination of canine rabies or (ii) elimination of dog-mediated human rabies. Countries chose the latter, as they did on the previous four occasions. Regardless of the scope of the goal, countries agreed to the recommendation that the new date for elimination had to be based on the systematic evaluation of countries' rabies capabilities. This approach to goal setting differs from the previous four that led to arbitrary elimination dates that failed to recognize the heterogeneous development of rabies capabilities among countries.

Proactively coordinated, the aggregated evaluation of countries' rabies capacities, and their improvement plans toward disease elimination should inform the earliest date at which the region would be able to eliminate the disease. Moreover, the aggregation of gaps from all countries would inform the regional demand for specific capacities, e.g., rabies vaccine, some of which could be more efficiently provided by a regional mechanism (e.g., PAHO's Revolving Fund) (1).

The development of a systematic evaluation framework of the countries capacities is thus critical. Such a framework would require the definition of regional standards and indicators as well as clear requirements regarding the nature and quality of the evidence needed to support control and elimination claims. A PAHO review of indicators used by the countries to monitor the performance of their rabies programs identified large heterogeneity, in the number of indicators per country, from just a few to more than 100, and in the nature of them, from process indicators to outcome indicators (2).

The importance of the regular REDIPRA meetings, which constitute the strategic governance platform of rabies programs in the region, cannot be underestimated. Group dynamics prevalent at these meetings exercise great influence on strategic issues that cannot be replicated remotely. Specifically, we stress the importance of peer-pressure among countries. In addition, regional coordination requires formal structures to facilitate regular networking in the interval between REDIPRA meetings, e.g., via working groups around specific products such as interlaboratory proficiency exercises (1).

On coordination, we must mention stakeholder engagement, even if briefly, and specifically one of the most salient actors in recent years, i.e., animal rights groups. The engagement of officials with these groups was not always productive and, at times, led to departures from the real focus on rabies control. But a change at both camps appears evident in recent years. Both sides have learned to moderate their message, and now understand that negotiation and not confrontation leads to better outcomes for all. Official programs start to recognize that these groups need to be brought to the discussion table at the planning stages, as they can deliver niche-specific approaches to local problems.

## On Evidence

The impact of interventions can only be monitored with reliable data. Since 1998, PAHO has been collecting data via questionnaires to the countries on their programs' performance prior to the regular REDIPRA meetings. It was only at the most recent REDIPRA in 2015 that a thorough analysis of the data could be presented (1).

Earlier reports stated that a number of Latin American and Caribbean (LAC) countries were conducting excellent rabies surveillance (3). These results seem to concur with those reported by zoonosis managers to a survey in early 2015 who replied that they were satisfied with the sensitivity of their rabies surveillance (4). However, to the best of our knowledge, and with the exception of Haiti (5), there is no systematic evaluation of rabies surveillance in the region, and we are not aware of recent patient chart reviews of acute encephalitis or sensitivity estimation of dog surveillance. Specifically on the latter, the region, by large, follows the recommendation of sampling a proportion of the dog population (3). This, at best, has facilitated discussions on the importance of targeting dogs for early warning and, at worst, has drained resources without informing the epidemiology of the disease. Recent work supported by PAHO questions this approach to surveillance and suggests more efficient alternatives (6). These studies also show the importance of variant identification, especially at the end game, and are a reminder that some countries in the region still lack this capacity in-house, or even nimble mechanisms to acquire it elsewhere for prompt response to cases.

The investigations that followed the recent occurrence of multiple dog cases in Brazil (7), spanning to more than one local authority, highlighted fundamental structural problems, not rabies-specific, for the generation of sound evidence, i.e., the absence of a common standard for data gathering across administrative units. This is likely to resonate in other countries, and it highlights the need for a standard epidemiological report. To that effect, the region will benefit from the ongoing efforts by Brazil toward the harmonization of processes across its network of zoonosis' surveillance units.

The regional rabies database, SIRVERA (8), despite all its shortcomings, has played a critical role in the success of the regional program. A perhaps overlooked contribution is that SIRVERA is the most tangible product of the program across its many years and participating countries. Together with other "brands" of the program (e.g., REDIPRA), SIRVERA has bundled the countries around the regional goal. That is, those countries that contribute data to it. Three countries where rabies is still endemic have consistently failed to report to SIRVERA. Such failure to report not only impacts on the ability of the program to monitor regional progress, but it has important consequences on neighboring areas pursuing control and elimination as they struggle to assess the risk of incursion from such countries. Like the other capacities, SIRVERA needs to change to adapt to the end game too and become the exhaustive repository of rabies programs performance indicators in the region. In other words, it Del Rio Vilas et al. Tribulations of the Last Mile

must not just chase cases but also track and identify substandard capacity planning and deployment that constitute the best early warning of rabies risk.

### On Resources

A prolonged epidemic tail, consecutive goal failures and farther in time goals, contribute to investors' fatigue (in the case of the Americas, these are mainly government budget holders, with external donors playing a much limited role, except for Haiti). It is a well-described fact that short-term goals lead to greater willingness to invest (9). The opposite can lead to reduced donor engagement. Efforts to attract resources must contemplate breaking down long-term regional goals, to reduce the long payback period, into country and area-specific objectives with short- and medium-term deliverables linked to enhanced capacity deployment to attract more investors/donors seeking quick returns. In other words, investment opportunities need to be indexed to processes and capacities that are fully measurable, tractable, and prone to direct influence. Moreover, short-term successes, e.g., the declaration of an increasing number of rabies-free countries and areas along the way, would reduce the perception of uncertainty around the overall investment for regional elimination, farther ahead.

Efforts to attract investment must also recognize that at the end game, there is little room for inefficiencies. As a result, optimization of regional and national resource allocation schemes, e.g., by country or geographical area vs. by capacity, merits study to prevent underperforming assets from receiving undeserved support (10, 11). This tendency may stem from failure to accept underperforming capacities relative to others, or a lack of appreciation of the full scope of opportunity costs. This might well be the case of devoting scarce resources to dog sterilization, an intervention that delivers a much lesser punch at a much greater cost than dog vaccination. Inefficient investment will only prolong the tail end of the epidemic, directly resulting in further cases and unnecessary deaths and, as a result, increasing the risk of goal fatigue. Other inefficiencies, either at the national or regional level, could occur as a result of maintaining vaccine production facilities for reduced domestic demand, unsubstantiated dog surveillance strategies that lead to no useful evidence for decision making, or the current prophylaxis schemes (PEP), promoting intramuscular administration, prevalent across the region.

### On Vaccination

Notwithstanding occasional problems, all countries in the region, except for those that have been free from rabies for years, plan the purchase of vaccine (for humans and dogs) in their annual budgets. This, in comparison with other regions, is a feast. Not all, though, manage to acquire the vaccine at all (most notably Haiti), or in the quantities and timelines needed. The insufficient deployment of vaccine, whether in control or elimination stages, is the ultimate reason as to why rabies persists in some of those countries. Insufficient dog vaccine deployment, due to deficient population coverage, untested vaccine quality, mismanagement of batches, and non-compliance with protocol, translates into failure to consistently achieve herd immunity in a number of scattered locations that remain endemic, even if undetected. Occasional donations and exchanges of vaccines between countries, whether brokered by PAHO or not, have been the norm in the past to supply vaccine to areas in acute need (3, 12). This solidarity may be threatened as more areas reach elimination in the region, and hence reduce the size of their rabies programs and vaccine stockpiles. In such a scenario, where one single exposure may delay the region's goal, a regional mechanism to guarantee rapid deployment of rabies vaccines merits consideration.

 Beyond the financial implications, these animals contribute to vaccine coverage indicators, despite bringing no additional immunity, and may lead to a false sense of achievement about herd protection in the targeted dog population.

Rabies programs across the region have benefited from the incorporation of human rabies vaccine in the countries' regular acquisition of biologicals through PAHO's purchasing mechanisms. In 2014, following recommendations from REDIPRA (13), PAHO also included the dog vaccine in its portfolio of biologicals on offer through the PAHO revolving fund. Via large purchases, PAHO guarantees the provision of quality vaccine at competitive prices, and, most importantly, promotes regular budgeting practices in the countries. Improvements are possible, for example, by incorporating human rabies vaccine in the well-established logistical systems of the Expanded Programme on Immunization in country. This is a work in progress after a communication by PAHO to that effect was sent to the countries last year.

Despite seeing the lowest human case count in over 30 years, the demand for human rabies vaccine is on the rise. If human vaccine sold by PAHO's purchasing mechanisms is a good proxy for the overall use across the region, bearing in mind that not all the LAC countries buy through PAHO, we have noted an average increase of over 55,000 doses of human vaccine every year for the period 2005–2015. In 2015 alone, circa of 900,000 doses were acquired via PAHO's revolving fund. Although alternative dog surveillance systems, such as those based on tracking exposures after reported bites, could lead to more efficient PEP application (6), rabies programs must prepare for long-lasting demand of PEP even in the absence of canine rabies cases for quite some time.

### On Awareness

In contrast to the evident scars left by smallpox, or other diseases with obvious sequelae, rabies does not leave living bearers to remind us of its occurrence. Together with the declining incidence, awareness of the disease will wane. This phenomenon will only get worse, and it would be important to regularly monitor the levels of awareness among the population in risk areas. Activities to that effect, e.g., knowledge-attitudes and practices surveys, may deliver collateral benefits by capturing heightened risk perception among the population that may provide sufficient reason, in the absence of adequate surveillance, for policy intervention.

A decrease in awareness may also lead to reduced uptake of preventive measures as seen in other diseases, e.g., measles vaccine. For rabies, the impact might be twofold: leading to reduced dog vaccination, and PEP uptake and prescription by health staff after exposure. The latter was the target of the recent rabies alerts issued by PAHO after a number of cases in the region (14). However, no similar alerts were issued after evidence of insufficient dog rabies vaccines coverage in risk areas. This, again, highlights the reactive nature of the program chasing cases and not capacities (or their absence).

### FINAL REMARKS

It has been said that the regional rabies elimination program is a victim of its own success, as reduced disease incidence leads to relaxation of controls, and new evidence needs at the end game challenge attitudes and practices that worked well during the control phase, but may not do so well during the last mile. Given the regional success, some resistance to accept innovations tested in other settings, as is the case of intradermal human rabies vaccine or the use of capture–recapture methods to estimate dog vaccine coverage, is expected. Transferring successful approaches from well-controlled projects in local settings elsewhere is not without difficulty as managers tend to dismiss them as generated from different contexts of little applicability to their own. This may be true, given well-known limitations in external validity of even the most robust investigations (15). However, the merit of these well-controlled studies elsewhere is undeniable, and the region is now benefiting from such findings in the formulation of canine surveillance guidance and area level classification.

Basic problem structuring theory identifies two types of complexities in every problem and decision setting to its resolution: technical or analytical complexities, and organizational complexities (16). For rabies in the Americas, where effective tools are available for its control and elimination, disease persistence is due to organizational failure at the planning, implementation, or evaluation of the rabies program. Specifically, failure to (i) gather and properly present the evidence about disease risk and vulnerabilities to budget holders, (ii) systematically generate synergies with other programs and stakeholders to ensure efficient capacity deployment, and (iii) conduct thorough risk assessment on the sustainability of the rabies program. We recognize the impact of externalities on any disease program, but for dog rabies and the Americas, the authors believe that contextual factors play a critical role in one country alone: Haiti.

Improvements are underway. The regional program has now developed a framework for evaluation of rabies capacities,

### REFERENCES

commissioned research to robustly guide dog surveillance requirements (5) and classify areas based on a composite measure of risk (17), and recently released a new SIRVERA platform capable of managing all the evidence needs in the elimination phase (8). These tools come with a price. They need increasing amounts of quality and timely data to provide the required precision, around results of interventions such as dog vaccine coverage, to support robust and opportune decision-making.

Reaching out to countries to promote reporting as per the new data standards and to support the shift in focus toward monitoring capacities and vulnerabilities, and not just cases, will require increased resources by the regional program. The additional resource will have to be distributed across endemic, at risk and free areas. Although the most obvious targets are the endemic and at risk classes, the region must also capitalize on those areas that achieve freedom. To that effect, the regional program needs to formalize the processes around rabies elimination and maintenance of such status and demand thorough risk analysis by countries that contemplate interventions beyond their borders in collaboration with areas still posing a risk.

Good as a planned approach may be, elimination requires more than cold preparation. Failure to reach the 2015 elimination goal should have generated a state of crisis to justify major transformational changes in the regional program. Without such changes, in the form of a state of urgency to propel the commitment to prompt elimination, the risk of apathy is real. Without consideration of the intangible benefits stemming from elimination, mostly of a political nature, the cold calculations around the diminishing returns of additional disease control measures at this stage may lead to the perpetuation of the current situation. This would betray the vision of those colleagues over 30 years ago. Without the pressure of an imminent goal, there are no regional consequences as a result of a new case, beyond the tragic death of a human being by a shameful disease.

The recently approved "Plan of Action for the elimination of neglected infectious diseases and post-elimination actions 2016– 2022" (18), should deliver the new impetus, and the resources, to reach rabies elimination by 2022. Of mention is the inclusion in this plan, for the first time, of a reference to the elimination of canine rabies transmission.

### AUTHOR CONTRIBUTIONS

VV conceived and wrote the work. All the authors have critically reviewed and revised the manuscript and approved it for publication.

of a novel surveillance program. *PLoS Negl Trop Dis* (2015) 9(11):e0004245. doi:10.1371/journal.pntd.0004354

**Conflict of Interest Statement:** The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The handling editor declared a past co-authorship with one of the authors MV and states that the process nevertheless met the standards of a fair and objective review.

*Copyright © 2017 Del Rio Vilas, Freire de Carvalho, Vigilato, Rocha, Vokaty, Pompei, Molina Flores, Fenelon and Cosivi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.*

# Eliminating Dog-Mediated Rabies in Sikkim, India: A 10-Year Pathway to Success for the SARAH Program

*Helen Byrnes1 \*, Andrea Britton2 and Thinlay Bhutia3*

*1Vets Beyond Borders, Brisbane, QLD, Australia, 2Vets Beyond Borders, Melbourne, VIC, Australia, 3SARAH Division, Department of Animal Husbandry, Livestock, Fisheries & Animal Health, Government of Sikkim, Gangtok, India*

A third of the world rabies burden is in India. The Sikkim Anti-Rabies and Animal Health (SARAH) program is the first state-wide rabies program in India and demonstrates a successful One Health model of dog-mediated rabies elimination. The SARAH program was created in 2006 as a collaboration between the Government of Sikkim and international non-government organizations—Vets Beyond Borders and Fondation Brigitte Bardot.  In 2005, there were 0.74 human rabies deaths per 100,000 (4 deaths) within Sikkim, and from 2006 to 2015, there were no human rabies deaths. In 2016, two human rabies deaths were reported near the West Bengal border region. From 2005 to 2010, the incidence of animal rabies is unknown; from 2010 to 2016, eight cases of animal rabies were reported. Major challenges for the program are continued commitment to rabies control in the face of 0 to low human rabies incidence and the risk of rabies incursions. Effective intersectoral communication between Health, Veterinary, Forestry, and Police officers is essential to enable rapid response to animal bite incidents and possible rabies incursions. An integrated One Health approach needs to be maintained with enhanced active rabies surveillance. Other states must establish similar programs if India is ever to achieve a goal of eliminating dog-mediated human rabies.

Keywords: SARAH program, Sikkim India, rabies elimination, One Health, mass dog vaccination, dog population management, animal welfare, surveillance

## INTRODUCTION

Globally, the incidence of human rabies deaths transmitted from dogs is estimated at 59,000 people, and a third of the world rabies burden is in India (1, 2). In India, there is no national strategy for the elimination of rabies (1), and rabies is not a notifiable disease. Recently, pilot programs for rabies control have commenced in the states of Tamil Nadu and Haryana (3–5), and a number of animal-welfare groups throughout the country include canine rabies vaccination in their activities. The state of Sikkim has implemented a state-wide One Health rabies program since 2006. Sikkim is a small Himalayan state in North East India bordered by Nepal, China, and Bhutan (**Figure 1**), with a population of 610,000 (2011 census) (6). The core components of the Sikkim Anti-Rabies and Animal Health (SARAH) program (the Program) are canine rabies vaccination, dog population management, and rabies prevention education, which have been shown to control and prevent

#### *Edited by:*

*Louise Taylor, Global Alliance for Rabies Control, USA*

#### *Reviewed by:*

*Tenzin Tenzin, National Centre for Animal Health, Bhutan Sarah Cleaveland, University of Glasgow, UK*

*\*Correspondence: Helen Byrnes*

<EMAIL_ADDRESS>
#### *Specialty section:*

*This article was submitted to Veterinary Epidemiology and Economics, a section of the journal Frontiers in Veterinary Science*

*Received: 31 October 2016 Accepted: 16 February 2017 Published: 15 March 2017*

#### *Citation:*

*Byrnes H, Britton A and Bhutia T (2017) Eliminating Dog-Mediated Rabies in Sikkim, India: A 10-Year Pathway to Success for the SARAH Program. Front. Vet. Sci. 4:28. doi: 10.3389/fvets.2017.00028*

rabies leading to elimination (7, 8). It also provides health care to street dogs and aims to foster a compassionate attitude toward all animals. The Program enjoys strong community support within Sikkim for its efforts in rabies control and improvements in animal welfare.

The SARAH program was created as a collaboration between the Government of Sikkim, Australian non-government organization (NGO)—Vets Beyond Borders (VBB), and French NGO—Fondation Brigitte Bardot (FBB) in response to the public of Sikkim requesting that mass shooting of street dogs cease and a more humane method of controlling the dogs be implemented. In 2005, human rabies incidence in Sikkim was 0.74 deaths per 100,000 persons, totaling 4 human deaths (**Table 1**). From 2006, there were no reported cases of human rabies until 2016. Two animal cases were reported in 2010; no further animal cases were reported until 2015. Data for reports of animal rabies cases are poor prior to 2010.

This paper provides a perspective on the implementation of the SARAH program for the control and elimination of dogmediated human rabies in Sikkim and the benefits and challenges of a One Health approach (7, 9, 10).

## DOG KEEPING IN SIKKIM

Sikkim is largely rural, with 47% of the state under forest cover. Seventy-five percent of the state's population reside in rural areas. The main urban center is Gangtok (**Figure 1**) with 100,000 people. Sikkim is a multiethnic state with strong influences of Buddhism (the state religion until Sikkim became an Indian state in 1975) and Nepalese Hindu. The majority of the population is Nepalese (11), and Nepali is the most common language spoken (12).

Dogs in Sikkim are traditionally kept outside as protectors against wildlife intrusion such as Himalayan bear, but also against bad spirits and adverse life events (13, 14). With increased standard of living most village households now keep one or more dogs. In villages, young puppies are often kept inside, and when older are kept outside and handled little. In urban areas, there is an increasing incidence of western-style pet ownership with dogs living inside as members of the family. Workers brought into Sikkim for contract jobs associated with construction of hydroelectric plants usually keep three to four dogs per household. These dogs are kept outside, free roaming and are often difficult to handle. When the contract is finished, the workers move away and usually leave the dogs on the street.

Free roaming dogs are common in Sikkim, and the supervision and responsibility felt for these dogs is on a continuum from nothing to full responsibility. Many family owned dogs are allowed to roam freely. A culture of quasi-ownership has been described in the city of Ranchi, India (15) where people feed roaming dogs but do not take responsibility for vaccination or sterilization, and dog catching with butterfly nets is required for vaccinating these dogs. Over the lifetime of the SARAH program, use of butterfly nets has reduced, and most dogs can now be caught by hand by the SARAH team or community members. While 42% of dogs were reported as stray in Tamil Nadu (5), on average in Sikkim 18% of the total dog population are unsupervised dogs for which no one takes responsibility and which require capture with butterfly nets. In South Sikkim where there are many contract workers, the unsupervised roaming dog population is 27% (**Table 2**).

There is also a population of feral dogs in the forests in the China border regions, which is likely to be derived from abandoned puppies from army camp dogs. Efforts are made to vaccinate and surgically sterilize these dogs in a trap and release program. The army has permitted access to army camps for the surgical sterilization and rabies vaccination of camp dogs to enable a buffer zone of vaccinated neutered dogs. The army has cooperated with improved garbage control in army camps thus eliminating a food source for feral dogs.

## COMMUNITY ENGAGEMENT

Sikkim Anti-Rabies and Animal Health community education on rabies prevention have been designed around core Buddhist and Nepali Hindu religious beliefs including animal sentience, the cherished relationship between people and dogs, and the role of dogs in providing security, and their loyalty and friendship. The Program recognizes that human–animal relationships are "economic, cultural, and emotional in nature" (16, 17) and that dog keeping practices and norms of responsible pet ownership vary in different localities and cultures and can change over time. Animal-welfare lessons were incorporated into early school syllabus in 2009, and further lessons will be incorporated in the 2018 syllabus. The Program has been very careful to address the felt needs of the community to generate community participation.

TABLE 1 | Program data on activities and incidence of dog bites and rabies cases, program funding, and volunteers.

*n/a, not available. Dog bite data provided by Sikkim Department of Health include potential rabies exposure associated with animals such as drinking milk from a cow bitten by a dog or jackal.*

*Vaccination coverage is based on dog population size estimates provided by village councils and Department of Animal Husbandry field officers. Feral dogs in forests are excluded from the data estimates.*

As trust in the Program has developed, the community is more aware of rabies, and societal norms of animal welfare have changed. Community members will now bring dogs for vaccination and sterilization or describe where they can be found enabling many of the unsupervised dogs to be vaccinated and sterilized. Family planning in women in Sikkim has been actively promoted by the Government (18), and the potential benefits of "family planning" in dogs in reducing the number of unwanted puppies and associated animal-welfare problems were quickly recognized by the community; the community reports fewer dog fights particularly during the breeding season. An increase in dog bite incident reports is seen twice yearly in dog breeding season (March/April and September/October), during the major festival in September/October and following rabies education activities.

Community participation and cooperation is integral to the Program. Key messages to encourage participation are (1) canine rabies vaccination is needed for control of human rabies, (2) surgical desexing will reduce dog roaming and fighting, and hence the risk of rabies, (3) canine rabies vaccination and sterilization are provided free of charge, (4) sterilization will reduce the number of unwanted puppies, and (5) if your dog is unvaccinated and bites a person, you may be held responsible by the Panchayat (local village council) and the affected person for the cost of PEP for the affected person. PEP is available free from public hospitals, but if it is unavailable at the hospital, it must be purchased from a private medical store. In the last 2 years, Panchayats have placed the onus of financial responsibility for PEP on the owners of unvaccinated dogs.

### STAGES OF DEVELOPMENT

The SARAH program has developed over 10 years with capacity building and government commitment from a small NGO-managed program relying substantially on international volunteers to a state-wide government program, providing a One Health model of sustainable dog-mediated rabies elimination.

## INITIAL STAGE

Initially, Program administration, veterinary volunteers, and training were delivered through VBB with a VBB Program manager present in Sikkim and 2–3 international volunteers assisting with the work throughout the year. FBB provided funding on a matching grant arrangement with the Government of Sikkim with the expectation that after 3 years the project would be taken over by the government. Government provided facilities for clinics and public education, accommodation for volunteers, and local staff for the project. A SARAH clinic was established for surgical sterilization, rabies vaccination, and treatment of sick and injured street dogs; mobile units enabled the Program to be extended to rural regions.

Initial and subsequent training activities had a strong emphasis on animal welfare and have been critical for community acceptance of the Program and cost control. Extensive training of local veterinarians in veterinary surgery and medicine, and local staff in animal handling and dog catching occurred through the formal VBB VetTrain© program. Volunteers provided mentoring, on-the-job training, and train-the-trainer programs to local staff. Important elements for community support for the Program were the adoption of humane catching methods, which cause minimal distress to animals and demonstrate a recognition of animal sentience and the significance of dogs in the community, good surgical outcomes with a low rate of surgical complications (<0.003%), rapid return of dogs to their home territory (within 24 h for healthy dogs), and commitment to treat all sick/injured street dogs.

In 2009, the Program became a Division of the Department of Animal Husbandry. VBB volunteers continued to participate, but VBB had a reduced role in Program administration; FBB provided reducing financial support (**Table 1**).

## INTERMEDIATE STAGE

Multisectoral cooperation is essential for sustained rabies elimination (19), accordingly, a seminar on rabies and emerging zoonotic diseases was held in 2009. Representatives from the government veterinary and medical fraternity of the State Government were invited; few medical personnel attended. There were two major outcomes from the meeting. The first was the establishment of the Wildlife Conservation and Feral Dog Program to prevent the spread of wildlife rabies into the dog population in Sikkim by creating a buffer zone of rabies vaccinated dogs in the border regions adjacent to China and Nepal.

The second decision was to implement an annual state-wide rabies vaccination campaign each September with World Rabies Day activities incorporated (pet shows, school activities, and media releases). Critically, the implementation of state-wide rabies vaccination extended the Program to the rural regions of Sikkim. Canine rabies vaccine is provided free of charge; annual rabies vaccination of pet dogs is compulsory under state legislation. Houseto-house vaccination was needed initially, but central vaccination posts are now feasible in most villages. A catch-vaccinate-releaseresight program is undertaken for street dogs with marking of vaccinated dogs with paint. An annual dog census is correlated with village council knowledge of dog numbers facilitating 70% vaccination coverage to be achieved in East Sikkim (20–22). Vaccination coverage by district is shown in **Table 2**.

A distemper outbreak occurred in 2012 resulting in the death of thousands of dogs and community fear that distemper was caused by rabies vaccine. Extensive community education was undertaken to ensure participation in subsequent rabies vaccination campaigns and encourage owners to vaccinate dogs for distemper.

A One Health Intersectoral Rabies Committee was established in 2012 to transcend sectoral boundaries, comprised of Departments of Health, Animal Husbandry, Forestry, Urban Housing & Development, Police, and Army. The tasks of the committee were to prepare a proposal for rabies to be a notifiable disease in Sikkim, formulate procedures for restrictions of crossborder dog movement, formulate procedures for dog registration, work with the National Centre for Disease Control to establish a State Surveillance Laboratory for rabies control, develop a surveillance system for achieving rabies, and improve garbage control. A major achievement was rabies becoming a notifiable disease in Sikkim in 2014 for animals and humans (23). Garbage management has improved with daily rubbish collection in major towns, and weekly rubbish collection in regional districts.

### CURRENT STAGE AND ONE HEALTH OUTBREAK RESPONSES

Both human and canine rabies were controlled in Sikkim during 2006–2015. Complacency developed about rabies as the perception of disease risk was low. The Health Department stopped stocking PEP and rabies immunoglobulin (RIG), and the need for rabies surveillance and development of laboratory capacity was given low priority.

In December 2014, two people and a number of dogs were bitten by a jackal in a village close to the West Bengal border. Dog brain samples were sent interstate for testing, but the results were inconclusive. In February 2016, there were reports of a jackal attacking cows near the West Bengal border. Two cows tested positive for rabies (**Table 1**). Subsequently, two suspect human rabies deaths were reported in a nearby village. One person had been bitten by an unvaccinated pet dog, refused medical treatment, and died. The other person had no history of dog bite and died in hospital. Laboratory confirmation was not undertaken reflecting problems previously identified in effective surveillance of rabies programs (24): inadequate training in sample collection, difficulties in getting samples to a diagnostic laboratory from Sikkim, and family reluctance to allow postmortem diagnosis.

### DISCUSSION

### Vaccination and Dog Population Control

Rabies vaccination of dogs is the cornerstone of rabies control (25, 26). The logistics of a state-wide vaccination campaign in the Himalayas are difficult. Cooperation of villagers, Panchayats, and Department of Animal Husbandry field officers is essential. Human-mediated dog movement and gaps in coverage are problems in effective rabies programs (27). Recent rabies incursions in South Sikkim occurred in areas where there is human-mediated dog movement, where they have been gaps in vaccine coverage (**Table 2**), and which is adjacent to West Bengal with no rabies program. A Program team is now permanently located in South Sikkim to improve vaccination coverage and dog population management.

Dog population management is important for the Program goals of improved animal welfare (28, 29) and rabies control; the numbers of dogs sterilized annually are approximately 20% of the dogs vaccinated in Sikkim each year (**Table 1**). It is also important because it addresses community concerns about dog fighting and nuisance, and unwanted puppies. Improved animal welfare supports a more stable dog population. Community assistance with dog catching enables a minimal although highly skilled dog catching team. The aides who assist with surgery are also the dog-catching team. This has enabled control of a major cost, for the size of the dog catching team can be a significant cost in a dog population management program (3).

### Intersectoral Coordination, Community Engagement, and Animal Welfare

Intersectoral coordination and communication, essential for rabies control (10, 19), is an ongoing challenge. The establishment of a One Health Intersectoral Committee provided the authority for SARAH to seek cooperation at district and village level. The perceived success in controlling rabies and dog population management together with wide community support facilitated cooperation at all levels, although an unanticipated outcome was the Department of Health's interim decision to stop stocking PEP and RIG.

Education on animal welfare and the obligation to care and value dogs has been associated with increased community participation and support for the Program. There is a temptation to assume that the animal welfare emphasis of the Program will only work in Sikkim where animal sentience is accepted and the complex relationship between people and dogs is acknowledged in festivals such as Tihar (Deepawali). It has been suggested that the important role of dogs in Hinduism may be an impediment for successful program adoption (30), but in Sikkim, it has facilitated program adoption. An increase in empathy and improved attitudes to animals has been shown to increase empathy to humans and facilitate prosocial behavior (31–36), which may in turn motivate health behaviors including participation in vaccination campaigns (28). A critical feature in the SARAH program is the recognition of the significance of human–animal relations and culturally appropriate framing of community education messages.

### Challenges Facing the SARAH Program

Recent suspect rabies cases highlighted the need for formal and regular intersectoral communication at community level, the need for improved epidemiological data, for enhanced active surveillance related to animal bites, training for appropriate medical response to suspect rabies dog bite, the logistical difficulties in getting both human and animal samples from Sikkim to a laboratory for confirmation of rabies, and the ongoing risk of rabies incursion and sylvatic rabies.

The seasonal pattern of the recent rabies outbreaks occurring at the border during winter when food sources are scarce suggests rabies incursions into Sikkim, rather than ongoing circulation of rabies within Sikkim. An effective surveillance system with tracing back of suspect animals is needed to confirm this hypothesis (37, 38). Increasing human wildlife conflict in Sikkim (6) may increase the risk of rabies transmission. If rabies were controlled in domestic dogs in surrounding areas, it is not known if jackal could sustain the circulation of rabies although Lembo (20) concluded that dogs were the only species essential for rabies persistence in the Serengeti. There are clear limitations in the accuracy of vaccination coverage estimates based on dog population size estimates provided by village council knowledge. However, the data suggest that vaccination coverages of 70% are likely to be feasible in Sikkim, as shown by consistently high estimates achieved in East Sikkim.

The SARAH program is a State Government supported program and lacks the international resources available to national programs. Effort is being directed at establishing low cost enhanced active rabies surveillance (37). The Rapid Test (BioNote) is used in the field when available. Discussions are being held with counterparts in West Bengal for extension of the rabies program into West Bengal, but resources are limited for both parties.

### CONCLUSION

The Sikkim Government, together with SARAH partner NGO— VBB and FBB, has made a considerable investment to eliminate dog-mediated rabies. The recent re-emergence of rabies in Sikkim highlights the imperative of an integrated One Health approach to increase the sensitivity of rabies surveillance and to ensure interruption of rabies transmission. The SARAH program is a model of rabies control in a predominantly rural environment with limited resources. It is also an example of the challenges encountered in maintaining rabies control in a landlocked state. Other Indian states must establish similar programs if India is ever to achieve a goal of eliminating dog-mediated human rabies.

## AUTHOR CONTRIBUTIONS

HB has been involved in the SARAH program since 2006. HB and AB researched, designed, and wrote this paper. TB has been local coordinator for the program since inception and provided expert and local knowledge about the paper subject.

## FUNDING

The Sikkim Anti-Rabies and Animal Health program is funded by the Government of Sikkim, India and Fondation Brigitte Bardot, France. The authors would like to thank the tireless efforts of the many volunteers from Vets Beyond Borders, Australia, who have worked in the program.

### REFERENCES

**Conflict of Interest Statement:** The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

*Copyright © 2017 Byrnes, Britton and Bhutia. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.*

# A Century Spent Combating Rabies in Morocco (1911–2015): How Much Longer?

*Sami Darkaoui1 \*, Florence Cliquet 2 , Marine Wasniewski2 , Emmanuelle Robardet 2 , Nadia Aboulfidaa1 , Mohammed Bouslikhane3 and Ouafaa Fassi-Fihri 3*

*1Division of Pharmacy and Veterinary Inputs, National Food Safety Office, Rabat, Morocco, 2ANSES – Nancy Laboratory for Rabies and Wildlife, French Agency for Food, Environmental and Occupational Health & Safety, European Union Reference Laboratory for Rabies, WHO Collaborating Centre for Research and Management in Zoonoses Control, OIE Reference Laboratory for Rabies, European Union Reference Laboratory for Rabies Serology, Technopôle agricole et vétérinaire de Pixérécourt, Malzéville, France, 3Department of Pathology and Veterinary Public Health, Agronomic and Veterinary Institute Hassan II, Rabat, Morocco*

#### *Edited by:*

*Lea Knopf, World Health Organization Switzerland*

#### *Reviewed by:*

*Philippe Soumahoro Kone, Ecole Inter Etats des Sciences et Medecine Vétérinaires, Senegal Mehdi Elharrak, MCI Santé Animale, Morocco*

> *\*Correspondence: Sami Darkaoui<EMAIL_ADDRESS>
#### *Specialty section:*

*This article was submitted to Veterinary Infectious Diseases, a section of the journal Frontiers in Veterinary Science*

*Received: 01 December 2016 Accepted: 04 May 2017 Published: 02 June 2017*

#### *Citation:*

*Darkaoui S, Cliquet F, Wasniewski M, Robardet E, Aboulfidaa N, Bouslikhane M and Fassi-Fihri O (2017) A Century Spent Combating Rabies in Morocco (1911–2015): How Much Longer? Front. Vet. Sci. 4:78. doi: 10.3389/fvets.2017.00078*

Rabies has no known beginning in Morocco and to date, government control efforts and plans fail to eradicate the disease. A review and analysis of available epidemiological data are crucial to learn lessons from the past and to propose effective actions. Legally, animal rabies is a notifiable disease since 1913 and legislation has been updated periodically since. Dogs have always been considered as both the disease's vector and reservoir, while cattle, other herbivores, and humans are victims. Animal rabies cases evolution from 1942 to 2015 is characterized by ascending phase then decreasing one following structured rabies control plan implementation in 1980s. Indeed, from 1986 to 2010, three rabies control plans have been conducted based on free of charge rabies vaccination of owned dogs through mass campaigns. The geographical distribution of rabies is stable over the years with highest cases number in rich rural areas and around cities. Human rabies cases are decreasing over the time (1976–2015) thanks to the opening of new antirabic treatment centers in the last decade which permit the administration of more PEPs. After a century of rabies control, Morocco registered an average of 301 animal cases and 21 human cases annually for the last decade (2005–2015). Few reasons led to those limited results. The lack in law enforcement and, moreover, the fact that the law do not take into account responsible dog ownership aspect are of importance. Lack of dog population knowledge and management and intersectoral coordination deficiency are additional failure reasons. The gathered data will help to build a new strategy with a focus on a "One Health" approach. Dog population ecology parameters' study is of primary importance. We estimated dog population to be 2.8 million dogs based on human:dog ratio. Enhancing vaccination coverage of dog population is feasible by combining parenteral vaccination and complementary oral vaccination. Updating legislation by inclusion of responsible dog ownership and law enforcement are crucial. Over the last century, Morocco registered a slow decreasing tendency in the number of animal and human rabies cases. Urgent strategy need to be implemented because rabies elimination is an achievable goal in Morocco.

Keywords: rabies, Morocco, epidemiology, dog, one health, vaccination coverage, dog population management

### INTRODUCTION

Rabies has no known beginning or starting point in Morocco (1). Several epidemiological studies have focused on this disease since the beginning of rabies vaccination among dogs in 1927 (2). They have provided a wealth of documentation covering a century of rabies surveillance in Morocco. Compilation and analysis of data are of importance to learn lessons from the past and to propose actions to be included in any new strategy.

Efforts to control rabies in Morocco began as early as 1911, year of the first human and canine rabies vaccination by a local vaccine manufactured at Institute Pasteur of Tangier (IPT) (1). Since that, routine antirabies vaccination of people and animals was practiced but without any improvement in the number of victims. The World Health Organization first launched initiatives to set up a rabies control program, supported by international experts, in 1980s (3–5). The program had an objective of rabies elimination through a certain number of actions related to human health, veterinary sector, and municipalities. The limited results led to other control strategies in 1990 and 2001. Despite these efforts, Morocco still recorded an average of 21 human rabies cases per year (2005–2015) (6) and since 1923, official documents have recorded the death of over 1,046 humans due to rabies and the exposure of over 838,660. The number of people having been given postexposure prophylaxis (PEP) is enough to fill a big-sized town such as Sale (city in north-west of Morocco, has a population of 850,403 according to the census of 2014, and is the fifth biggest city of country).

The rabies situation in Morocco affects not only Moroccan citizens but also neighboring countries. The density of trade with Europe exchanged by road is a source of rabies contamination for several rabies-free European countries. A number of cat and/ or dog owners illegally smuggle their pet(s) into Europe mostly by road through Spain, disregarding all the legal provisions concerning the transportation of animals into Europe and not declaring their animal(s) to the customs officials or veterinary border control staff (7–10). From 2001 to 2015, 12 rabies alerts have been notified in Europe originating from Morocco (eight in France, one in Belgium, one in Germany, one in the Netherlands, and one in Spain) (10).

An analysis of the experience of the past century should reveal lines of action in order to make better headway; future strategies should also be able to benefit from scientific and technical progress in the field of rabies control (11). Morocco is a developing country and should choose the most efficient means of control in order to reduce the costs incurred by rabies (12) and eliminate the risk of exposing the Moroccan population to this fully preventable disease.

### MATERIALS AND METHODS

### Rabies Regulations

A review of the regulatory texts on rabies published between 1913 and 2014 in Moroccan official journal1 is realized with focus on the legal status of rabies. The key points of each text are presented and general evolution of legislation related to rabies is discussed.

### Epidemiological Analysis

Epidemiological data concerning animal and human rabies cases were collected from published bibliographical references and epidemiological reports issued by the competent public authorities, and more especially those of Morocco's National Food Safety Office (ONSSA) for animal rabies cases and the Ministry of Health for human cases. In the event of contradictory data from different sources, the highest figure has been chosen due to the substantial risk of underreporting (13). The epidemiological characteristics of animal rabies in Morocco are discussed for the period from 1928 to 2015. There follows a presentation and discussion of the rabies patterns in Morocco (reservoir, animal species affected, seasonal changes, and geographical distribution) as well as measures taken at different times to tackle the disease and the suggestions of various authors in order to improve the situation. Mapping of the evolution of the number of animal rabies cases in the Moroccan provinces was performed using ArcGIS 10.1 software. The number of human rabies cases reported annually from 1974 to 2015 is analyzed and discussed. There is a discussion on the geographical distribution of cases of human rabies. The provided PEP protocol is discussed as well as the laboratory diagnosis. Propositions of improvement are formulated. A review of the genetic characterization of rabies virus isolates in Morocco is realized. Molecular epidemiology data are compared with classical epidemiology findings.

### National Rabies Control Plans (NRCPs)

Different NRCPs are presented. The achievements and deficiencies of plans are presented and the causes of their limited success analyzed.

### Moroccan Dog Population

It is crucial to remain informed about the dog population in order to draw up a realistic and effective canine rabies control plan. A synthesis of the studies that are interested in the size of the Moroccan canine population is carried out in order to have an estimate of this population. This is based on a comparison between the results of estimations of the dog population in the framework of an amendment to the 1993 rabies control plan, the NRCP of 2001–2010 and other international studies or studies in Maghreb countries. The data are extrapolated depending on the human:dog ratio chosen in order to estimate the size of the dog population. Demographic data were provided by official Moroccan authorities (Health Ministry website: http://www. sante.gov.ma). The current state of dog population control and suggestions for improvement are also presented.

### Vaccination Coverage of the Dog Population

The vaccination coverage of the dog population is estimated by combining data on vaccination in urban areas by private veterinarians with that in rural areas following government-run mass vaccination campaigns. Dog population data are related to the estimated human:dog ratio. Vaccination coverage is analyzed and suggestions put forward on how to improve the situation. Data on

1http://www.sgg.gov.ma.

vaccination in urban areas were extrapolated from the number of doses of rabies vaccine sold between 2009 and 2015 to veterinarians in the private sector. The data were obtained from veterinary pharmaceutical companies with a rabies vaccine registered in Morocco2 during the same period. Propositions for dog population vaccination coverage amelioration are formulated with reference to Moroccan experiments in oral dog rabies vaccination.

### Application of the "One World, One Health" Concept

The "One World, One Health" concept is highlighted by international organizations such as FAO, OIE, and WHO as the most efficient way of controlling zoonotic diseases. The actions taken in Morocco are assessed in the light of this concept, examples, and suggestions given.

### RESULTS AND DISCUSSION

### Rabies Regulations in Morocco

Morocco has a wealth of regulations on animal rabies control with a new text every 9 years. These regulations were first focused in people treatment after rabies exposition on IPT (14) and at antirabies institute of Marie-Feuillet hospital in Rabat (15). The measures were also concentrated on prevention of exposure to rabid animals either imported (16) or locally by instigating measures (17) to control stray dogs in both urban settings (18) and the countryside (19). Parenteral vaccination of dogs was already mandatory in 1928 (20) early and quickly after OIE 1927 conference on rabies and mandatory antirabies vaccination of cats was instaured on 1934 (21).

This basic regulatory framework has been updated in several occasions either within mandatory notifiable animal diseases list update in 1977 (22) or by updating specific measures to control rabies in 2000, 2005, and 2014 (23–25).

This regulation evolves from the vizirial orders in 1915, 1927, 1928, 1934, 1936, to decrees in 2000, 2005, and 2014, which have more regulatory weight.

The regulations cover mandatory rabies vaccination of dogs and measures to be taken in the event of contamination but they do not cover management of the dog population or the concept and actions of "responsible dog ownership". The latter concept implies registering and identifying dogs, preventing their negative impact on society and controlling breeding. The legislation should also cover mass control actions for stray dogs (means of capture and humane euthanasia) in accordance with OIE rules on animal welfare (26).

It should be noted that national regulations are not fully applied. The mandatory vaccination of dogs is not monitored and there are no legal sanctions should a dog be found to be unvaccinated (25).

### Epidemiological Analysis

The first rabies vaccination was performed in Morocco in 1911 by a rabies vaccine for human and veterinary use produced at IPT

2www.onssa.gov.ma.

(1, 27). Since that, exposed people were treated and from 1923 to 1932 a total of 361 people received PEP in IPT (21). The number of exposed treated people increased to reach an average of 1,500 person per year between 1951 and 1958 (28).

Veterinary authority started dogs preventive antirabies vaccination in 1928 and an average of 671 dogs per year were vaccinated between 1928 and 1933 (27, 29). This number increased to reach 10,000 dogs per year between 1945 and 1965 (30).

An average of 302 (minimum 68 and maximum 663) animal rabies cases was registered between 1942 and 1968 (28, 31–33) demonstrating an active animal rabies surveillance system based on Casablanca laboratory.

**Table 1** summarizes the data relating to the 1971 to 2015 period concerning animal rabies, the number of dogs vaccinated and culled, the number of human cases, and the number of people given PEP. We can identify an increasing trend of animal rabies cases number up to 1982 from where this trend decreases. This can be visualized in **Figure 1**, which traces evolution of animal rabies cases, number of vaccinated and culled dogs from 1942 to 2015. The animal rabies cases number follows a distribution with an ascending phase in which the number of animal rabies cases increases and a descending phase from 1982. The year 1982 coincides with start of WHO rabies fight in Maghreb zone (3). Those efforts led to first NRCP (1986–1990) launch. **Figure 1** shows also that the number of vaccinated dogs per year increases considerably in the beginning of the control plan rising from 2,730 dogs in 1982 to 25,000 dogs in 1983 and 229,231 dogs in 1989. This figure then dwindled before increasing once again during the amended rabies control plan of 1994, reaching 325,780 dogs. Similarly, a peak of 450,917 dogs vaccinated was reached in 2005 under the 2001–2010 rabies control program. This evolution in the number of vaccinated dogs in peaks during the maximal activity of different rabies control plans is characteristic. The decrease in the number of vaccinated dogs is thought to be linked to the veterinary services efforts to control other livestock diseases (**Figure 1**) (5, 34).

Up to 1992, the number of dogs culled was always greater than the number of dogs vaccinated. Since 1992, the culling of dogs has been stopped in the context of rabies control but is still practiced to limit the problem of stray dogs in urban environments (**Figure 1**).

Several studies have investigated the epidemiological status of rabies in Morocco. We selected the nine that we considered most relevant and which cover the period (1928–2015) (2, 6, 28, 29, 33, 35, 37, 56, 57). Several of the epidemiological characteristics of rabies in Morocco appear stable over the studied period (1928–2015).

#### Rabies Reservoir and Affected Animal Species

**Table 2** contains data on the different species involved in animal cases from 1951 to 2015.

Since the very first epidemiological studies on rabies in Morocco (2, 29), dogs have been shown to be the reservoir and dog bites the primary source of human contamination. Since 1951, a number of 8254 dogs in all have been diagnosed as rabid, accounting for 51% of all animal notifications (**Figure 2**). The proportion of dog cases in the total animal rabies in Morocco TABLE 1 | Number of animal rabies cases, number of vaccinated dogs and culled dogs, number of PEPs, and number of human rabies cases from 1971 to 2015.

*a Discordant data.*

*bData provided by the ONSSA/DSV Epidemiology and Health Monitoring Service. c Data provided by the Epidemiology and Disease Control Directorate of the Moroccan Ministry of Health.*

*ND, not determined.*

*Blue color: data for the period before implementing the first NRCP. Orange color: data for the period after implementing the first NRCP.* decreases over the time passing from 82% in 1951 to 20% in 2015 (1951: 82%, 1964: 76%, 1973–1983: 52%, 2000: 45%, 2007: 32%, 2010: 25%, and 2015: 18%). This can be explained by the fact that veterinary services give more attention to rabies diagnosis on livestock because of its economic value (35) and concentrate less on the known vector (i.e., dog).

All the authors agree that herbivores (cattle, sheep, goats, equids, or camelids) are victims. Notifications of rabies in cattle come second to notifications concerning dogs in all the studies (4,244 cases, i.e., 26% of animal rabies cases). Contrary to the tendency evolution in dogs, diagnosis pressure on herbivores (cattle, ovine, goat, horses, and camels) is growing over the time passing from 12% in 1951 to 79% in 2015 (1951: 12%, 1964: 19%; 1973–1983: 43%, 2000: 47%, 2007: 64%, 2010: 65%, and 2015: 79%). This is probably, as previously said, because of economic value of livestock (35) that imposes a close surveillance.

Several studies have emphasized the role of cats in human contamination (21, 33, 35). In all, 800 cats have been notified as rabid and account for 5% of total registered animal rabies cases between 1951 and 2015.

Rats are regularly mentioned in diagnosed cases and even quoted as a rabies reservoir in natural surroundings (33, 37), but since 1980s, they have no longer been named in reports and are classified in the "Others" category of **Table 2**. Indeed, WHO considers that this species does not play an epidemiological role and is rather an epidemiological dead end (59).

Morocco is the natural environment for some 30 bat species (order *Chiroptera*, families *Rhinopomatidae*, *Emballonuridae*, *Nycteridae*, *Rhinolophidae*, *Hipposideridae*, *Vespertilionidae*, and *Molossidae*) (60, 61). To date, as far as we know, rabies has never been detected among these species, and no bats have never been reported as a source of human contamination in Morocco.

#### Seasonality of Rabies

In 1959, Chevrier (28) noted an annual cycle of animal rabies cases, with one peak in the spring and another in the autumn. The link between the cyclical nature of cases and the sexual cycle of bitches was only described in 1985 (35). To date, this seasonal variability is stable.

Several authors (28, 38) have pointed out a cyclical increase in the incidence of rabies every 6–8 years. No explanations have ever been provided for this cycle, which appears to have been broken after the instigation of the first NRCP from 1986 to 1990.

#### Geographical Distribution

No regions of Morocco are free from the disease. Rabies is a rural disease, 80% of notifications originating in the countryside and only 20% in towns. In rural areas, it is most often found in a 30–50 km perimeter around major towns rather than in remote areas of the countryside or mountainous regions where there are fewer people (28). Chevrier's observations have been confirmed by all the studies that have followed and are still relevant today (6).

The close relationship between the density of the human population and that of the dog population is also highlighted as a risk factor, because the denser the human population, the denser the dog population too and the higher the risk of exposure

FIGURE 1 | Evolution of animal rabies cases, number of vaccinated and culled dogs (1942–2015). AHS, African Horse Sickness; FMD, Foot and Mouth Disease; BT, Bluetongue disease; PPR, Peste des petits ruminants disease.

TABLE 2 | Animal rabies cases per species from 1951 to 2015.

*a Data related to laboratory confirmed animal cases in Casablanca laboratory.*

*Data from 1997 to 2015 provided by the ONSSA Epidemiology and Health Monitoring Service.*

to rabies (28). The dissemination of the rabies virus along road networks was revealed by Fassi-Fehri et al. (37). These data were later confirmed by molecular biology research in 2010 (62).

**Figure 3** shows geographical distribution of animal rabies in Morocco provinces for 1997–2001, 2002–2006, 2007–2011, and 2012–2015. The five most badly affected provinces according to 1976–2015 period data were Sidi Kacem (703 cases), Kenitra (608 cases), Safi (532 cases), Casablanca (492 cases), and Meknes (488 cases) [(35) and ONSSA Epidemiology and Health Monitoring Service]. The geographical distribution of cases shows that rabies is endemic to the whole of Morocco with the exception of desert regions (southern provinces). It may be seen that the distribution of rabies cases is related to the intensity of farming activities, thus confirming that Chevrier's observation in 1959 (28) is still valid in 2015.

### Human Rabies

The vaccination of humans following exposure to the rabies virus was first practiced in Morocco by IPT (1). From 1923 to 1932, 361 people in all were treated (21) and from 1951 to 1958, this figure increased to 1,500 people treated on average

per year (28) and continued to rise from 3,156 in 1964 to 10,209 in 1973 (36). The number of people treated per year was more or less stable between 1977 and 2003, averaging 13,789 (38, 41, 42, 44–48). From 2004, this figure more than doubled, reaching an average of 29,163 people from 2004 to 2015 (data provided by the Epidemiology and Disease Control Directorate of the Moroccan Ministry of Health). The human rabies is a notifiable disease in Morocco since 1967 (63).

**Table 1** and **Figure 4** present the annual number of human rabies cases and the number of persons who received PEP from 1971 to 2015. The number of human rabies cases is slightly decreasing over time: the annual mean of human cases for 1976 to 1985 is 31 (min = 14 and max = 52), dropping to 23 (min = 16 and max = 34) for 1986 to 1995, then 22 (min = 15 and max = 30) for 1996 to 2005, and finally 21 (min = 16 and max = 24) for 2006 to 2015. The number of persons who received PEP increased in the same time: from 1986 to 2005, there were 14,633 PEPs per year on average (min = 10,496 and max = 23,564), but this figure has more than doubled, reaching an annual mean of 30,687 (min = 25,857 and max = 35,279) for the period from 2006 to 2015. This is no doubt thanks to the efforts of local communes which, under the impetus of the Ministry of the Interior (64), have opened new rabies treatment centers, whose numbers have risen from 120 in 2008 to 147 in 2012 (56, 63).

Up to now, Morocco has applied the 2-1-1 protocol for PEPs by the intramuscular route (63). This could increase by 60–80% the number of people treated for the same budget in rural areas if it used the intradermal delivery of fractioned doses recommended by WHO (65). It has been proven that poor people often do not spend time and money traveling to receive PEP (66).

Generally speaking, human rabies in Morocco matches the geographical distribution of animal rabies (35). Dogs are the main species responsible for human contamination (91% in 1935, 80% in 1965, 95% in 1973, and 80% in 1985) (2, 30, 35, 37). The frequency of contamination is greater among the male population (around 80%) and among young people (around 40% among children less than 15 years old). Bites often involve the legs (around 45%), face (around 15%), and hands (around 35%), all other locations (such as the neck or genitals) being rarer (35, 37, 38).

Although, as previously said, the number of human rabies cases of rabies is decreasing, it should be remembered that official notifications are generally underestimated (13) and that they may only concern hospital cases (37). There is a need to investigate the origins of underreporting and give feedback after detailed analysis over several years of the files on human deaths. This would reveal weaknesses in the system and possible means of improvement. One of the reasons of underreporting could be the population's refusal to allow an autopsy of their loved ones for cultural reasons. Alternatives to autopsy by non-invasive methods such as skin biopsies or supraorbital sampling could lead to an increase in the number of rabies cases reported and provide the diagnostic laboratory with precious samples (66). A report following a 2-week WHO expertise carried out in 2001 in different places of Morocco (67) as well as a study (39) revealed that human deaths are linked to an inadequate prophylaxis and suggest an improvement of training of physicians in antirabic centers.

Morocco has one diagnostic laboratory for human rabies, which only uses postmortem analytical methods. It confirms about 30% of clinical cases (63). The use of quick new reliable tests (lateral flow or immunohistochemical methods) in local, non-specialized laboratories (66) could help increase the rate of laboratory confirmations.

### Genetic Variability of the Rabies Virus

Since the rabies virus was first sequenced in 1995, the Moroccan strains have been identified as belonging to genotype Africa 1 (68). The RabMed Control project included a phylogenetic study of 133 samples of canine rabies from 28 Moroccan towns between 2004 and 2008 (62). This study revealed:

### National Rabies Control Plans

Since 1980s, several different NRCPs have followed in succession:

	- Raising awareness among the public and providing health education (causes, seriousness and consequences of rabies, reasons for and scope of the control measures proposed).

As the plan progressed, this component was not strictly and constantly applied. From 1991 to 1992, the general rabies vaccination campaigns were not carried out because this period coincided with the outbreak of both African horse sickness and foot-and-mouth disease, which mobilized substantial human and material resources (**Figure 1**). From 1996 to 1998, the rabies vaccination of dogs was limited to campaigns isolated both geographically and over time (5). Consequently, the results fell well below the vaccination coverage targets set by the NRCP (i.e., 70–80% of the dog population).

– *NRCP covering 2000–2010:* this plan aimed to reduce the number of rabies cases within 5 years. The longer-term objective was to eliminate rabies within 10 years and ensure that the country then remained rabies-free. The strategy proposed, which is based on a generalization of medical prophylaxis supported by targeted health prophylaxis, required a change in regulations, regular awareness-raising activities among the general public, training, and retraining of the main players and the setting up of a national epidemiological surveillance network.

Finally, a system to assess the proposed strategy was set up (5). This plan led to the vaccination of a maximum of 450,917 dogs in 2005 (5). The apparition of various health crises in the livestock sector led to veterinary services control efforts to combat or prevent the diseases by intensifying surveillance and/or vaccination campaigns (sheep pox vaccination campaigns in 2002, 2004, and 2006, avian influenza surveillance in 2005 and 2006, bluetongue vaccination campaign in 2007, and PPR vaccination campaigns in 2008, 2009, and 2010) (34). This prevented the plan from reaching its objectives.

Despite the limited effect of these different plans on the status of rabies in general, they nonetheless laid the foundation for future actions:

Since 2014, WHO, OIE, and FAO—supported by the Institut Pasteur network—have launched an initiative to eradicate rabies

in North Africa in general, and Morocco in particular, by around 2020. This initiative is supposed to materialize the implementation of the concept (71). Since the initial kickoff workshop in 2014, the actions in the framework of this initiative have not yet been communicated.

The parenteral vaccination of owned dogs in rural settings has been the key measure in rabies control programs in Morocco since 1911 (1). However, this measure was rapidly revealed to be insufficient in the light of the tiny proportion of dogs vaccinated compared to the size of the total dog population. The culling of dogs as a means of controlling the dog population was suggested in 1935 (2). This twofold mechanism, involving the vaccination of dogs and culling of stray dogs, is still carried out today in Morocco.

Several reasons for the failure of this strategy have been identified from 1938 on and are still relevant today:

Several judicious proposals have been put forward by various authors from 1935 on to improve the situation and are still relevant:

### Moroccan Dog Population

Several authors (5, 13, 72–74) have underlined the importance of a good estimation of the dog population in the success of rabies control programs. According to WHO, the size of the dog population may be estimated through the human:dog ratio (59). Studies of the dog population carried out in Morocco in 1993 assessed the human:dog ratio at 5.93 in rural settings and 25.36 in urban settings. In 1999, the ratio was found to be 7.93 in rural settings and 80.94 in urban settings (5). More recently in 2013, estimations of this ratio for North Africa gave 3.84 in rural settings and 9.83 in urban settings (73) and for Africa in general, 7.40 in rural settings and 21.20 in urban settings (13).

To estimate the current dog population, we chose the mean of national dog population estimates obtained in 1990s and international estimates obtained in 2005 and 2013, giving a human:dog ratio of 6.14 in rural settings and 34.33 in urban settings. This value is no doubt biased but the bias is acceptable. By applying the calculated human:dog ratio and taking into account Moroccan demographic data (the Moroccan population being estimated in 2015 at 34,271,622 in all, including approximately 13,458,258 in rural settings and 20,813,364 in urban settings) (data from target populations of health programs. Health Ministry website http://www.sante.gov.ma), we may conclude that the dog population is estimate to stand at 2,798,126 (of which 2,191,930 in rural settings and 606,195 in urban settings). This number could be overestimated but we consider that it is better to overestimate the target population rather to underestimate it.

It should be noted that generally speaking, there are few data about Moroccan dog population features (sex ratio, mean age, and life expectancy of an owned or stray dog). Although Moroccan legislation requires dog owners to vaccinate their pets, it remains silent on the management of this population, as mentioned earlier. Neither does it inspire responsible ownership in order to prevent dogs creating a nuisance within the community.

Managing the dog population is a complementary measure in rabies control and reducing the dog population does not directly affect the transmissibility rate (R0, i.e., the reproduction number) of the rabies virus (75). This runs contrary to the idea that canine rabies can be eliminated by reducing the density of the dog population (59, 66). This reduction in density is frequently achieved through culling campaigns that often prove counterproductive and have a major impact on animal welfare (11). Indeed, dog owners frequently begin hiding their dogs, moving them to other areas, or indeed acquiring new dogs to replace those killed. This behavior is linked to the need for dogs, itself related to their function. In Morocco, dogs are mainly used as guard dogs, to watch over livestock (31%), a combination of both (87%) or to hunt (2%) (76). Dog movements help disseminate the rabies virus, as reported in Indonesia (75) and North Africa, including Morocco (62). Furthermore, dogs that are easy to vaccinate are those that are the easiest to cull, thus reducing the dog population's immunity (66).

Dog sterilization campaigns are a key tool in the management of unwanted dogs. They reduce the trouble caused by dogs, along with their aggressive behavior and thus dog bites. They improve the human population's acceptance of free-roaming dogs and improve the health and life expectancy of dogs in a roaming population (77). Sterilization would increase the effectiveness of vaccination campaigns by stabilizing the size of the dog population and reducing its renewal rate. It is an important complementary measure in a rabies control program whose key thrust is vaccination coverage (66).

Currently, Moroccan communes are responsible for taking measures to prevent animals from roaming free. They must collect, check, and impound stray dogs in compliance with article 50 of the Communal Charter (64).

However, these functions are not fulfilled in most towns and those communes where they have developed various systems:

There are several possible ways of getting out of this situation, alone or in conjunction depending on local conditions:

international partnership between Morocco and Spain on hygiene and public health (93).

## Vaccination Coverage of the Dog Population

The most efficient means of preventing human rabies cases is to reach a 70% vaccination coverage of the dog population (12, 66). The vaccination coverage rate of the dog population in Morocco can be estimated by dividing the total number of vaccinated dogs by the total dog population, calculated by adding together the following two figures:

It should be noted that the vaccination coverage from 2009 to 2015 never exceeded 6% of the total dog population. Urban vaccination coverage fluctuates between 6.51 and 8.25%, while rural vaccination coverage fluctuates between 2.47 and 5.73%