Rabies in Haiti

Rabies is a viral disease that exists in Haiti and throughout the world. It often causes fatal inflammation of the brain in humans and other mammals, such as dogs and mongooses in Haiti. The term "rabies" is derived from a Latin word that means "to rage"; rabid animals sometimes appear to be angry. Early symptoms can include fever and tingling at the site of exposure, followed by one or more of the following symptoms: violent movements, uncontrolled excitement, fear of water, an inability to move parts of the body, confusion, and loss of consciousness. Once symptoms appear, death is nearly always the outcome. The time period between contracting the disease and showing symptoms is usually one to three months; however, this time period can vary from less than a week to more than a year. The time between contraction and the onset of symptoms is dependent on the distance the virus must travel to reach the central nervous system.

Haiti is one of five remaining countries in the Americas where canine rabies is still a problem, and it has the highest rate of human rabies deaths in the Western Hemisphere. Following the 2010 earthquake, rabies caused an estimated two deaths per week. Only a small number of these rabies deaths were reported to health authorities due to the impact of the earthquake, limitations in testing capacity, and lack of awareness and education about the disease among Haitians.

Epidemiology
Globally, 59,000 people die from rabies each year. This is the equivalent of one person dying every nine minutes, with half of the people who die from rabies being under the age of 15. The Pan American Health Organization (PAHO) and the Pan American Center of foot-and-mouth disease (PANAFTOSA) led a mission to eliminate dog-mediated rabies in the American region by 2015. These organizations are cognizant of the regional control of rabies. The PAHO and PANAFTOSA visited Haiti in early December, 2013, and the objectives of the mission were to assess the status of Haiti's rabies program as delivered by the Haitian Ministry of Agriculture, Natural Resources and Rural Development (MARNDR) and the Ministry of Health (MSPP). The mission was to seek opportunities for collaboration between Haiti, Brazil, and the Centers for Disease Control and Prevention (CDC) in Haiti.

Even in 2017, rabies in Haiti is still identified as a national problem, even with PEP proposed.

Treatment
In Haiti, few cases of human rabies are reported to health authorities. In 2016, a report of a woman who had been exposed to rabies three months prior and was showing symptoms went to the hospital where no treatment was administered to her. Even after being reported to both the CDC and the national Department of Epidemiology and Laboratory Research (DELR), as required by Haiti's surveillance program, the woman died. This goes to show the lack of communication and effectiveness in caring for human subjects in Haiti, and the continued focus is on eliminating dog-mediated rabies altogether.

Human diploid cell culture rabies vaccine (HDCV) and purified chick embryo cell culture rabies vaccine (PCEC) are used to treat post-exposure immunization against a human rabies infection. Recommendations for treatment are given by governmental health care organizations and in health literature. Health care providers are encouraged to administer a regimen of four 1-mL doses of HDCV or PCEC vaccines. According to the CDC, these injections should be administered intramuscularly to persons who have not yet been vaccinated for rabies.

For those who are unvaccinated, the first of four doses is administered immediately after exposure to the rabies virus. Additional doses are given three, seven, and fourteen days after the first vaccination. Exposure usually means a bite from a rabid animal.

At an individual patient level, post-exposure prophylaxis (PEP) consists of local treatment of the wound, vaccination, and administration of immunoglobulin, if necessary [3]. At the program level, several components are critical, including: adequate and prompt recognition of the need for PEP by the public, if exposed, and by health officials, prompt and sufficient availability of high-quality PEP, and adequate follow-up of PEP use. Health officials' awareness of the need for PEP after a dog bite can only be achieved if the exposure is attended to immediately and communicated effectively.

Animal treatment
Dog vaccination is most effective for controlling dog-mediated rabies. This can be seen throughout the region of the Americas where medical authorities have achieved rabies control.

In Haiti, the United States Centers for Disease Control (CDC) is mainly focusing on dog-mediated rabies. Specifically in collaboration with the NGO Christian Veterinary Mission, the CDC has trained, to date, more than 20 MARNDR laboratory personnel in rabies diagnostic methods (Direct Fluorescent Antibody [DFA] and Direct Rapid Immunohistochemistry Test [dRIT]). The organizations have also improved a diagnostic laboratory in Port-au-Prince by providing it with advanced equipment. The surveillance system is a bite-reporting model where the public and medical providers report bite events to rabies control officers. In addition, more than 30 field veterinary and health agents were trained in rabies surveillance, in support of this effort.

In 2011, the CDC along with MARNDR initiated a five-year rabies infrastructure improvement program that focused on surveillance, diagnostics, and education. The MSPP also helped out by improving public education on rabies. Because Haiti has a gross national income per capita of US$1,035, it is the only country in the American region that is part of the group of low-income countries. The World Bank has classified 33 other low-income countries in Africa and Asia, where dog-mediated rabies is a major problem and results in thousands of deaths annually. The persistence of dog rabies is connected to limited resources and weak governance.

In conducting a rabies assessment, rabies control officers try to locate the offending animal. Animals that have bitten a victim are either euthanized and tested or quarantined for 14 days while remaining in their owner's residence. In addition, animals who show signs of rabies are tested, regardless of human exposure. This surveillance program is restricted to two of the ten geographical departments of the country (West and Artibonite) for security reasons. The area includes approximately 50 percent of the Haitian population. The CDC and the NGO Christian Veterinary Mission support the mission by maintaining four Haitian staff in the West Department and three in the Artibonite Department, respectively. Results of this mission showed the level of under-reporting of canine rabies. Specifically, six cases of rabid dogs in early December, 2012, were reported for the country.

During the first nine months of the surveillance mission, 42 rabid dogs were identified in just three communities in Port-au-Prince during the first nine months in 2012. That being said, no laboratory-based surveillance exists for the human population that is exposed to rabies and all diagnoses are based on clinical history. This is because of the lack of laboratory facilities, making it difficult to identify evidence for the virus in humans and shed light on the disease as a whole for them, in Haiti. There are insufficient numbers of pathologists to collect samples for human rabies, as well. There do exist other methods for viral antigen detection that may merit study.

In 2013, the CDC and its partners began an animal rabies surveillance program in several regions of Haiti and saw an 18-fold rise in detection of rabid animals. In 2015, the CDC evaluated Haiti's canine rabies vaccination program and found that only 45 percent of dogs were vaccinated, far short of the 70 percent needed to stop the spread of rabies in the dog population. In addition, the researchers found that Haiti had nearly 1,000,000 dogs, twice as many as previously thought.

The CDC and its partners had already begun a dog vaccination trial in evaluating the best vaccination methods for dogs in Haiti. As a part of this effort, they vaccinated 3,000 dogs in just four days during the summer of 2016 and planned to vaccinate a total of 8,000 dogs as part of this campaign.

Challenges
In Haiti, the control of dog rabies is led by the MARNDR while the MSPP manages health-care and rabies prevention in the human population. The separation of these ministries makes it easier for responsibilities to be divided among them. Communication about finding the source of exposure and implementing control methods to prevent further cross-species transmission is also more effective. This task is difficult enough within departments of the same ministry, (e.g., health care and epidemiology), which can be seen in experiences elsewhere. This is why a comprehensive evaluation of Haiti's rabies program should heavily consider the costs and benefits of this separation of responsibilities between the two ministries early on.

Despite a planned mass vaccination for dogs in 2013, no campaign was actually conducted. Authorities in Haiti relied on funds donated by the World Bank for the purchase of approximately 500,000 doses of inactivated, injectable vaccine (IMRAB by Merial). Although the funds were awarded in April 2013, the vaccine itself did not arrive until 2014 when the dog vaccination finally went underway in September 2014. The process as a whole was expected to terminate in January 2015. The lack of manpower needed to deliver faster implementation made it impossible for the campaign to be completed in less than four months.

Another challenge presented is vaccination failure, which usually leads to recurrent rabies in dogs and inconsistent control of the disease. The failures that disrupt annual campaigns or have insufficient coverage, for example, are seen as the main cause for this problem. Another factor is that in Haiti, dog vaccinations have been inconsistently applied. Back in 2012 when the last mass vaccination was led by the MARNDR, approximately 400,000 dogs were vaccinated. With this in mind, considering a current human population of approximately 10,000,000, a relation of one dog per ten people, and aiming to attain 70 percent of vaccine coverage, 700,000 dogs would have to be vaccinated. Assessing the effectiveness of this vaccination campaign is difficult because the dog population figures are unreliable (estimates range from 800,000 to 1,200,000 dogs), and though the overall success seems to be limited.

The number of rabid dogs detected by the MARNDR, MSPP, and CDC is a huge risk to people and is not accurately reflected in their surveillance figures. Although international support is common in both technical help and donations, it is not comprehensive. In addition, the MARNDR, MSPP, and other actors do not communicate effectively because of human resource limitations. That being said, the 2015 elimination goal in the region was compromised and control of the disease could not yet be achieved, despite the efforts of resolute national officials. In conclusion, rabies in the dog population is still a problem and major threat to the Haitian population. <!--==Funding== Funding:MFM, JBPL, and RW received no specific funding for this work. EC, VJDRV, JMR, JLP, and Contributed to the work as part of PAHO regional technical cooperation role, for which general funds exist. Both CDC and PAHO had a role in the studydesign and other stages. CDC support the dog surveillance activities, and PAHO the mission to Haiti(for EC and VJDRV), involvement of colleagues from PAHO Haiti office (JMR and JLP) and Panaftosa(OC). Neither PAHO nor CDC supported the ministries or their employees (MFM and JBPL).Competing Interests:The authors have declared that no competing interests exist.

gathered during the mission that comprised a review of the evidence and control plans to date, compare them against the basic capacities of a comprehensive rabies programme, and discuss-the findings in the light of the elimination goal in the region by 2015.

Section one and intro
The Context PAHO’s regional programme of rabies control defines Haiti as a priority country, i.e., countries where canine rabies variants are either circulating or did so in the recent past. The context and capacities of priority countries are diverse, and efforts are undergoing to evaluate the best port-folio of actions to address country-specific limitations [2]. Brazil, for example, remains a priority country because of the persistent, albeit well-circumscribed, occurrence of dog-mediated human rabies in the northeast of the country, in the state of Maranhao [3]. Even with this occurrence,

Brazil
remains a successful example in the control of dog-mediated rabies, and constitutes an important technical reference in the region. With the aim of promoting south-to-south collaboration, the Ministry of Health of Brazil, the ministry solely responsible for the control of dog-transmitted rabies in the country, assisted PAHO’s mission to Haiti. Specifically on rabies, Brazil has donated human and canine vaccines to Haiti in the past. One of the objectives of the PAHO mission was to explore ways to enhance this collaboration, for example, in the form of direct technical assistance on the ground. Such assistance would complement the activities currently conducted by the CDC.

To help with this basic capacity, the CDC has conveyed to the MSPP its willingness to assist in human sample collection, shipping of samples, and diagnostic testing at CDC’s rabies laboratory in Atlanta, Georgia, US. To date, only one sample has been shipped to the CDC, which tested negative for rabies.At a meeting during the mission, MSPP officials reported three human cases in 2013, eightin 2012, 13 in 2011, and one in 2010, all allegedly due to canine rabies. These numbers indicate severe under-reporting when compared with modeling figures that show Haiti as the main contributor of the estimated 200 human deaths by dog-transmitted rabies per year in the region[3]. The above structural limitations do not extend to animal samples that are analysed at the MARNDR rabies laboratory.

Tosupport the vaccination campaign, MARNDR is implementing a solar-powered cold chain(Fig 1), over and above the available cold chain facilities in MSPP field premises, previouslyused to support dog vaccination campaigns.

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On this note, dogbites are now, together with six notifiable conditions, part of the daily reporting requirements from 114 health units (out of more than 900 in the country) to a central epidemiology unit in Port-au-Prince, the capital. This intensive reporting pressure on health officials should increase rabies awareness across the health system, and lead to an increase in the number of dog attacks reported. The aggregation of this information, analysis, and feedback to the sources on a regu-lar basis would further improve awareness among health officials of the rabies risks.As reported by health officials, 1,657 dog bites were recorded in 2013 by the 114 sentinelhealth centers. For a population of approximately 10 million people, this results in a 0.016% of the population bitten by dogs; five times lower than the 0.08% average reported by the coun-tries that attended the 14thmeeting of National Rabies Programme Managers (REDIPRA inSpanish) in Lima (Perú) in 2013 [7], and many more times lower than the 1.8% reported inother countries where canine rabies is also endemic [8]. Analyses of the number of animalaggressions reported by the public may inform the level of awareness within the populationwith regard to the risk of rabies. A simple and short questionnaire about the motivation of thevisit by the dog bitten patient, i.e., whether it was related to fear of rabies, could be administeredto refine this inference. Further checks on the quality of the data should help explain apparentreporting artifacts, such as the fact that all registered victims of dog attacks were five years oldor older, a finding that challenges results elsewhere that consistently report young children asPLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0003806 June 25, 20154 / 10

chidren
the main victims of dog bites [9,10,11]. The surveillance artifact may hide greater under-reporting of rabies cases if this population group is not captured by the bite registration mecha-nisms, and should trigger questions as to where do children younger than five years old go forbite treatment.At the time of the review, the MSPP had more than 15,000 doses of human vaccine for PEPin stock. These vaccines belonged to a lot of 20,000 Vero cell rabies vaccines for intramuscularadministration donated by Brazil in 2013. This volume of vaccine should be enough to coverthe needs of the country for at least two years given the current use rate of 8,000 doses per year.In addition to sufficient numbers, vaccine must be stored in adequate conditions and in such away that allows its prompt availability across the country.

A national consultant hired byPAHO/Haiti visited twelve sites in Port-au-Prince during the last months of 2013 and reportedadequate cold chain. We had no data about the conditions outside the capital.At an annual use rate of 8,000 human vaccine doses (as per PAHO/Haiti’s warehouse rec-ords), the country could face a surplus of several thousand doses by the end of their shelf life inearly 2015. Solutions to the adequate use of this potential excess of vaccine, before they reachtheir expiration date, might contemplate increasing the distribution of vaccine to areas where itis not currently available, e.g., outside the capital. According to MSPP officials, all large hospi-tals in the country (between 40 and 50) had stocks of human vaccine. Ensuring that vaccineFig 1. Solar panels at an outpost in Haiti.Electricity is fed to refrigerators inside the post to ensure cold chain for canine rabies vaccine.doi:10.1371/journal.pntd.0003806.g001PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0003806 June 25, 20155 / 10

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regimens after exposure are taken fully by as many patients as possible is also critical. MSPPofficials confirmed that they do not record this key performance indicator. At the time of the mission, the amount and availability of any stock of immunoglobulin was not ascertained.Pre-Exposure Prophylaxis The 2013 WHO expert consultation on rabies report [3] indicates the administration of pre-exposure prophylaxis for those populations at continuous or high risk of rabies, especially children. Although the current stock of vaccine could support such strategy, and indirectly reduce the potential surplus of vaccine by 2015, the logistics of the distribution, rationale for application, and the required follow-up would make this operation impossible given the current avail-able resources.Outbreak Control Activities This capacity comprises surveillance, awareness raising, and control specific activities, within a defined time and space context, implemented following the confirmation of a case of rabies.These can include enhanced surveillance of animal populations at risk, ring vaccination, and awareness campaigns for the population. The rabies national plan provides protocols to guarantee the exchange of information between MSPP and the MARNDR after the occurrence of rabies events.

For example, the communication of dog attacks by the MSPP to the MARNDR, for the latter to initiate surveillance and control activities, occurs after a number of dog attacks are recorded for a specific area. At the time of this review, it was not possible to ascertain the criteria, e.g., number of dogs and period of time that trigger this communication, nor was it possible to verify the completeness of epidemiological reports around the cases.Reactive vaccination of susceptible animals after confirmation of rabies within the local community is also part of these case control activities, however, the amount of canine vaccine available for this purpose at the time of the mission, around 1,000 doses, appeared insufficient. Education Rabies educational capacity comprises activities towards health professionals and the general public to enhance and maintain awareness of rabies risks.

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To this end, the MSPP conducted a training activity for 40 health officials of the central region on PEP in 2013. This training fol-lowed four similar courses delivered in 2012. It was not possible to ascertain if these activities were all part of a training plan.MSPP and PAHO/Haiti officials stated the critical importance of training for health official son PEP, data form completion, etc., and stressed the ongoing need for these activities given thehigh staff turnover. Training on PEP application should help to change the current practice of delaying prophylaxis after exposure if the animal can be observed. This practice can lead to fatal delays [3] and it needs to be replaced with the immediate application of PEP after expo-sure even if the animal can be observed.For MARNDR officials, there are currently no training plans, although the CDC trained more than 30 veterinary officials in June 2013, and delivers regular training to personnel of theMARNDR laboratory responsible for rabies diagnosis.Identification of Other Risks Cases of canine rabies together with the significant numbers of mongoose cases reported from the Dominican Republic could be seen as a threat to Haiti’s rabies status [7]. Despite this beinga genuine concern, and an indication of a source of rabies in Haiti’s wildlife, it is not high in PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0003806 June 25, 20156 / 10

the list of priorities given the many limitations affecting the other capacities. Any medium- orlong-term strategy in the future must contemplate the wildlife source. In the short term, enhanced communication and coordination of control efforts with the neighbouring Domini-can Republic would bring benefits to the two countries.DiscussionDespite having a National Rabies Plan for the period 2007–2012, and an evaluation of it in 2011, little of the plan could be delivered due to insufficient resources at the MSPP andMARNDR. Whereas in other countries in the region the main interest resides on how rabiescontrol activities are operationalised, as the focus is on the optimization of well-establishedprocesses, in Haiti this is not the case, as some basic rabies capacities are still wanting. This istrue for the episodic mass canine vaccination campaigns, and the lack of diagnostic facilitiesfor human rabies cases. Given that canine vaccination is the most effective measure to controldog-mediated human rabies, the intermittent nature of the mass campaigns and their insuffi-cient coverage will not allow for the control of the disease any time soon, let alone itselimination.The inconsistent and insufficient canine vaccination campaigns will also stop short of deliv-ering a number of related positive effects associated with vaccination, e.g., increased awarenessin the population due to the high visibility of the campaigns, and a sense of purpose among theofficials responsible for rabies control. Not only that, the ongoing occurrence of dog cases dueto low levels of immunity in the population, despite large logistic efforts, can easily lead to frus-tration among officials and hamper participation by the population [12].Following recommendations from the 14thREDIPRA meeting [7] canine rabies vaccine hasbeen recently added to PAHO’s Revolving Fund (RF). Countries in the region can now requestcanine vaccine from the RF.

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Despite the advantages provided by the inclusion of the caninevaccine in the RF, e.g., consistent vaccine quality and more competitive prices, the evidence tosupport the allocation of funds within the MSPP and MARNDR to purchase rabies vaccine isnot sufficient. This evidence can only be gathered by means of adequate surveillance to informthe burden of rabies against that of other diseases.Although there are models that estimate a much larger number of human rabies cases inHaiti [3], these cases remain unobserved, and lead to no reaction by the already overstretchedand under-resourced Haitian health system. This appears logical as the impact of these esti-mated, but unobserved, cases is difficult to demonstrate relative to that of other conditions thatprovide counts of actual data and lead to health care expenditure. Disease estimates adjustedfor under-ascertainment trigger little policy action [13], at least at the operational level, and arenot a substitute for actual surveillance data. The dog surveillance work conducted by theMARNDR with technical support by the CDC is, therefore, critical. Short of reliable records onthe real count of human rabies cases, measures of rabies risk approximated by the dog surveil-lance figures, in combination with dog bite data, can provide an indication of the much higherlevel of rabies exposure in the population.Surveillance findings need to be disseminated to attain their objective: inform and influencedecision, at as many levels as possible. There is value in reporting back to the sources of data for awareness and motivation reasons, to local authorities to inform strategic and operationaldecisions pertaining to the rabies programme, and to international forums to raise awareness about the situation in Haiti. To this end, Haiti should return to the regular reporting of surveil-lance figures and details of the cases to the regional database on rabies (SIRVERA) held atPANAFTOSA [6]. By having up-to-date data by country and aggregated figures, PAHO canreport progress towards the goal of elimination in the region, and identify countries in need ofPLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0003806 June 25, 20157 / 10

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greater focus, such as Haiti. At this critical stage in the race to elimination, with fewer cases and diminishing resources and available skill pool in the region, collecting and sharing as much information as possible on the epidemiology and, critically, on the processes leading to the surveillance and control of the disease remains as important as ever.Following from the recommendations of the last REDIPRA meeting [7], PAHO coordinated in 2014 a proficiency exercise for 35 laboratories from 23 countries to assess regional consistency in direct fluorescent antibody techniques.

Haiti’s MARNDR reference laboratory has participated in this exercise. This shows the commitment of the Haitian authorities to improve their processes. This willingness should be extended to seek the utilization of the MARNDR laboratory premises for the diagnoses of human rabies cases, over and above legitimate administrative and organizational concerns. On this note, as of July 2014, there is discussion about developing a plan for a joint human and animal rabies diagnostic facility in the North Depart-ment. If successful, this will represent the second animal rabies diagnostic facility and first human rabies diagnostic facility in the country. The initiative to create a joint human/animal rabies diagnostic laboratory would maximize the use of the limited human resource and infra-structure capital. Given the current low recognition of human rabies, and the fact that the majority of routine diagnostic testing will be on animal samples, it is not feasible to create diagnostic facility solely devoted to human diagnostics, nor train personnel in human rabies diagnostics alone.

Brazil again
The Brazilian Ministry of Health is willing to help Haiti by extending its donations of vaccine to on-field technical support. This includes aiding areas that are planning vaccine campaigns, administering PEP training, and more. This contribution will add to the increasing need for a strategic framework with clear objectives like controlling dog-mediated rabies first to ensure the efficient elimination of dog mediated human cases, and coordination between donors. The impact of missions like this appears reduced in terms of observing rapid changes in response to limitations that are well known by the local officials.

The benefit could come in the form of notes like this and their dissemination:to increase awareness among international donors, senior authorities in Haiti, and within PAHO. A planned communication campaign is just one of the activities contained in the strategic document, being drafted at the time of writing, to support a rabies task force in Haiti. Keyto this strategy, and responding to a critical lack of this capacity, is the need for coordination among the multiple partners that deliver rabies activities in Haiti. Better integration among partners should lead to greater impact and more efficient use of resources. Coordination and speaking with one voice before Haitian authorities would also increase the critical mass of rabies control efforts and deliver a more consistent and rotund message. The funding of a rabies coordinator/rabies champion, who will work primarily towards ensuring regular and sufficient canine vaccination campaigns and prompt availability of human vaccine for the next two to three years, is being discussed at the time of writing.

The current situation in Haiti clearly impacts the region’s 2015 elimination goal [1] as it was not achieved. The countries of the region will have to make a new goal that recognizes the distinct situations across the region. Most of the areas where dog-mediated human rabies is no longer a public health problem will benefit from efficiency gains and enhanced knowledge management to ensure institutional memory and experience dissemination. These efforts should also benefit the reduced number of countries and areas, such as Haiti, where rabies remains a public health concern. Specific plans for dog rabies control, such as those described above, will require contributions from a number of regional partners and neighboring countries. The PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0003806 June 25, 20158 / 10

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forthcoming 2015 REDIPRA meeting will provide the platform to hold these discussions and agree on a new regional goal.A general limitation of the findings described here is that they originate from unstructured questions, observations, and notes from meetings and field visits. A more comprehensive plat-form to collect precise information on the levels of performance within the capacities, as well as on process-related indicators, is the subject of current work by PANAFTOSA.-->