While the world was busy dealing with the spread of pH1N1 in 2009, Mother Nature did not sleep. We handled several events that could have posed an additional unwanted distraction to the global public health community in the midst of pandemic response. Below is one example.
Introduction: Venezuelan Equine Encephalitis
Venezuelan Equine Encephalitis (VEE) is a zoonotic, mosquito-borne, aerosol-transmitted viral disease affecting humans and equines, the latter of which serve as amplifying hosts. The VEE virus is an RNA virus in the genus Alphavirus of the family Togaviridae, and is serologically classified into six antigenic subtypes (I–VI) and five antigenic variants (types AB-F).1 Subtypes IAB and IC are the only ones associated with significant human and equine epidemics. VEE is considered endemic to many areas of Central and South America. 1,2
Epidemics of VEE have occurred periodically in humans and equines in Latin America since the early 1920s. The largest documented epidemic began in Colombia in 1967 and spread by land to Ecuador and Venezuela, then moved northward through Central America and Mexico until it reached Texas in 1971. It is believed aggressive mosquito control and vaccination prevented the virus from spreading further into the United States. The epidemic involved close to 231,000 human cases in Colombia and Ecuador alone, with at least 310 deaths documented in the latter country.2,3 Although epidemic VEE has not been diagnosed in the United States since its last appearance in 1971, there remains concern that VEE could be used effectively as a bioterrorism agent.4-6
The 1995 Epidemic of Venezuelan Equine Encephalitis
In 1995, an epidemic of Venezuelan equine encephalitis (VEE) occurred in South America, resulting in 75,000 to 100,000 human cases of the disease and more than 300 deaths in Venezuela and Colombia.7,8 The actual number of human cases is unknown because of poor reporting from indigenous groups located in the Guajira peninsula shared by Venezuela and Colombia. 1,5 Likewise, equine deaths due to the disease were reportedly significant, but reliable estimates of the number of horses affected are unavailable. 7
In April 1995, the epidemic began in equines in Falcón state, located along the northern coastline of Venezuela. By the end of July, human transmission had been documented, with cases detected south and west of Falcón in the states of Lara, Carabobo, Yaracuy, and Zulia. By August, the epidemic had already spread to the Guajira peninsula in the far west of Venezuela on the border with Colombia. Through the end of 1995, scattered cases continued to appear in the southern and western Venezuelan states of Trujillo, Portuguesa, Cojedes, and Guarico. 7 The epidemic in Venezuela is estimated to have spread at a rate of 5 km per day, ultimately covering a geographic area of approximately 200,000 km2. 7-9
Overall, the state of Zulia was hardest hit, with approximately 10,000 human cases, 101 of which were confirmed by virus isolation. 2,7 At the time of the epidemic, emergency control measures, including restriction of equine movement, equine vaccination, and insecticide fumigation, were enacted to stop the spread. 4,9-11
Coincidentally, analysis of satellite imagery indicated enviro-climatic conditions had declined during this time as well, which was the beginning of the dry season. It is believed the geography of the area contributed to inhibiting spread of the virus, where the Cordillera de Mérida mountain range with peaks as high as 16,342 feet formed a perimeter around the epidemic zone. Most of the range is above treeline. The snow season of this mountain range coincided with the peak of the epidemic in July-August. Where the last stand of epidemic containment occurred, the Guajira peninsula, the Montes de Oca and Serrania del Perija mountain ranges form a valley with the Sierra Nevada de Santa Marta mountain range on the Venezuelan border. This could have served as a “funnel”, channeling the epidemic deep into the heart of Colombia, where potentially millions could have been infected.
Although the origin of this particular epidemic has yet to be determined, several theories were proposed to explain the periodic emergence of VEE: (1) evolution of epidemic strains from enzootic progenitors, (2) circulation of epidemic viruses as subpopulations within enzootic strains, (3) continuous circulation of epidemic viruses in cryptic cycles, (4) reemergence of epidemic strains from latent infections, and (5) reemergence of epidemic strains from incompletely inactivated vaccines. Additionally, there were speculation at the time that the 1995 epidemic was caused by an accidentally released laboratory strain. 1
Several key conditions in Venezuela contributed to the 1995 epidemic, including diminished equine vaccination coverage, lack of surveillance, limited knowledge of equine encephalitis, and increased viral activity following smaller VEE epidemics in Trujillo and Zulia in 1993. 2,3,12 Furthermore, unusually heavy rainfall was noted in both Venezuela and Colombia, the highest in 18 years. The heavy precipitation, coinciding with the apparent 15- to 20-year periodicity of major VEE epidemics in Venezuela and Colombia, appears to have favored an overproliferation of Aedes taeniorhynchus, Psorophora confinnis, and Anopheles aquasalis vector mosquitoes by enhancing their breeding sites. 7-11,13,14
In 1995, the total annual number of inbound passengers from Venezuela to the United States was 749,274, a 100 percent increase over the number in 1990. A seasonal peak of inbound air traffic was observed in August 1995. This seasonality was noted for 1990 to 2003, inclusive, as well. 15
Caracas was the main source of traffic to the United States in 1995 (641,975 annual inbound passengers), followed by Maracaibo (81,923) and Porlamar (16,938). Of particular note, Maracaibo was proximal to the epicenter of the 1995 epidemic and was a potential source of disease translocation to the United States. In addition, although international statistics identify Caracas as the main traffic source, the data fail to account for passengers who traveled to Caracas from other areas of Venezuela, then continued abroad. The top destinations in the United States were Miami, New York City, and Puerto Rico, with 572,380, 114,896, and 49,698 annual inbound passengers received from Caracas, respectively.
These statistics suggest that the United States was vulnerable to the translocation of a serious pathogen in 1995, much as New York City was vulnerable to West Nile virus in 1999. However, no signs of such translocation were reported. A variety of factors may account for this circumstance. First, it is possible that the pathogen never arrived, because no infected mosquito, equine, or human being was ever transported to the United States. Second, it is possible the pathogen was transported to the United States, but did not cause VEE, because the number of horses infected was insufficient to sustain an epidemic, because an infected human who did come to the United States was never bitten by a transmission-competent mosquito. Third, it is possible that the pathogen was transported to the United States and did cause VEE, but there were no syndromic surveillance systems in 1995 that could detect it. We had no indication if or when Miami Dade county or the Florida State Epidemiologist were aware of the events in Venezuela. Regardless, it is our conclusion that the United States was fortunate to have escaped an introduction of this virus.
It remains our assessment that as far as the United States and Canada are concerned, VEE represents another potential next-West Nile virus translocation threat. The concern is not just whether the virus is capable of translocating and triggering an epizootic in the receiving localities, but also may gain ecological establishment. We are fortunate an equine vaccine exists to assist in epizootic control should this occur.
Outbreak of Equine Encephalitis in Colombia (2009)
On June 8, 2009, we reported implementation of countermeasures for equine encephalitis in Río Viejo, Bolívar State, Colombia. These countermeasures were implemented on June 5th; it was unknown precisely how long the outbreak had been present. Sources noted health officials were involved in addition to veterinarians. Countermeasures reportedly included fumigation efforts, a vaccination campaign, distribution of mosquito nets, and an education campaign directed for people who lived near the farms where positive test samples were identified. The vaccination campaign was specifically targeted towards the local horse, mule, and donkey population.
The exact type of equine encephalitis was not specified, although a 2001 epidemiological bulletin by the Colombian Ministry of Health noted that outbreaks of VEE occurred in Colombia in 1995, 1998, and 2001. Colombian agricultural officials had an established routine cycle of VEE vaccinations for the local equine population that occurred every two years during the months of July and August. The Colombian government in May 2007 noted four cases of equine encephalitis in Bolívar State were recorded in 2006 and indicated Río Viejo was one of the municipalities most affected by vector transmitted encephalitis in Bolívar State. The diagnostic etiology of equine encephalitis recorded in Bolívar State in 2006 was not specified.
Outbreak of Equine Encephalitis in Belize (2009)
We reported on 3 September the Belize Ministry of Health had increased vector control activities in Belize, Cayo, and Stann Creek districts due to Venezuelan equine encephalomyelitis (VEE) activity on 31 August. The sources reported a "surge" of VEE activity specifically in the Cayo District between July and August 2009. Four villages in the Cayo District reported cases of equine VEE, although exact locations and case counts were not specified. Countermeasures were implemented quickly: 224 horses in Cayo District have been vaccinated along with 19 horses in Belize District and 19 horses in Stann Creek District. Response efforts also included animal movement control and "control of wildlife reservoirs."
According to a Veterinary Officer of the Belize Agricultural Health Authority, there were "a few" cases of equine encephalomyelitis in Belize every year, although information regarding the current incident was released due to an increase in the number of identified cases. In addition to an above normal number of cases, the sources note that the current distribution of cases is also greater than normal. Sources reported one isolated case was identified in Belize District in January 2009, while another isolated case was identified in Stann Creek District in April 2009. The National Veterinary Services Laboratory, a reference laboratory for the World Organization of Animal Health (OIE), had confirmed an unspecified number of cases in Belize, Cayo, and Stann Creek districts.
Additional reporting by the Belize Ministry of Agriculture and Fisheries recommended that all horse owners in Belize vaccinate their horses against equine encephalomyelitis. The source reported that the United States Department of Agriculture, National Veterinary Services Laboratory had confirmed that both VEE and Eastern equine encephalomyelitis viruses were currently circulating in Belize. The report specifically cited outbreaks in the Belize, Stann Creek, and Cayo Districts, although the number of cases is not reported. The source noted that additional cases were expected due to the current rainy season in Belize occurred between June and November. The Belize Agricultural Health Authority had previously identified outbreaks of equine encephalomyelitis in 2007 and 2005, although specific information regarding the prior outbreaks was not reported. The OIE had also previously reported an outbreak of Eastern equine encephalomyelitis between October and November 2005 that infected one horse in Teakettle, Cayo District.
On 16 September the Quintana Roo State Committee of Animal Health across the border in Mexico went on alert due to the situation in Belize. Officials moved to implement preventive countermeasures to prevent the introduction of equine encephalitis to the state. Sources at the time noted no cases of equine encephalitis had been detected on the Mexican side of the border. Response measures included increased surveillance efforts along the border with Belize and the implementation of "health cordons." Sources indicated that health documents were required to enter Mexico, although it was unclear if this measure applied to horses, humans, or both.
Outbreak of VEE in Costa Rica (2009)
On 3 September, we reported the Director General of the Costa Rican Ministry of Agriculture and Livestock, National Animal Health Service, had confirmed five equine cases of Venezuelan equine encephalomyelitis (VEE) on a farm in Liberia, Liberia County, Guanacaste Province, including one fatal case on 31 August. According to the sources, a total of nine susceptible horses were located at the farm, although only five confirmed cases were reported. The first confirmation of the Liberia event was received on 25 August, although the start date of the event was reported as 28 July 2009. The diagnostic test results were received from the Laboratory of Virology at the Veterinary School of the National University in Costa Rica. The sources did not report the strain of VEE involved in the incident. In response to the cases, health officials had implemented quarantine efforts, movement control measures, vector control measures, and vaccination measures. A total of 150 horses have been vaccinated in Guanacaste Province in response to current VEE activity in Guanacaste Province. Information regarding the cases was reported in conjunction with information on three additional equine VEE cases at two additional locations. The additional cases were identified in Capulín (2), and Rodeíto (1), both in Liberia County.
VEE Threat Assessment Process
We were concerned about several factors:
1. Connectivity to the US by direct, non-stop air traffic:
-Multiple cities in Colombia are connected to the US by direct, non-stop air traffic: Barranquilla, Bogota, Cali, Cartagena, Medellin, and Pereira. These US cities are the recipients of this traffic: Atlanta, Fort Lauderdale, Houston, Los Angeles, Miami, New York, and Newark. Key traffic nodes are Bogota and Miami in terms of number of unique connections.
-Belize and neighboring Quintana Roo State, Mexico are major international tourism sites. Atlanta, Dallas/Ft. Worth, Charlotte, Houston, and Miami are all connected to Belize City by direct, non-stop air traffic.
-San Jose, Costa Rica is connected to Charlotte, Los Angeles, Phoenix, Newark, Dallas/Ft. Worth, New York, Atlanta, Houston, and Miami. Liberia, Costa Rica (where VEE was confirmed) is connected to Dallas/Ft. Worth, Atlanta, Houston, and Miami.
2. Endemic mosquito transmission competency at the potential receiving sites. Particularly in the state of Florida and coastal Texas (Houston, Galveston, Corpus Christi and points south), VEE transmission competent mosquitoes are present.
3. Presence of equine populations at the potential receiving sites.
4. Environmental synchronization of the recipient sites. Transmission of VEE is a temperature-dependent process, and the temperature profiles of many of the receiving cities were optimizing or fully optimized for transmission.
5. Unsensitized public health and medical community. By “unsensitized”, we were aware the majority of the US public health and medical establishment were primarily sensitized to pH1N1, not other exotic biological threats. Further, we were well aware (as evidenced by the pandemic warning experience) that the tactical warning process was flawed- we believed it a challenge to fully sensitize Florida in particular if the need presented it. It was reassuring to see Miami/Dade County did have VEE on its notifiable disease list, however it is highly debatable if the medical community would be sensitive to report pediatric viral encephalitis without a prior sensitization step provided through an advisory. More likely to get such reporting from equine veterinarians at the race tracks.
We notified CDC, PAHO, and OIE of these events, as well as other NGO ground partners in Colombia, Belize, and Mexico in an effort to sensitize the community to be watchful for indications of an expanding epizootic. This notification was a “for your information” as opposed to a full warning. We believed it probable the involved strain of VEE was enzootic- specifically serotype IE- and not epizootic, and equine herd immunity in Colombia was likely high enough to inhibit transmission, especially if additional vaccinations, mosquito control, and heightened surveillance were occurring. Evidence of an expanding epizootic (i.e. loss of containment) that included human infections would have prompted more aggressive steps in the warning process. It is fortunate these indicators were not observed. We were sensitive to the profound crisis fatigue already seen in the public health and medical community and did not believe it prudent to add unnecessary stress.
As a final key point, no laboratory test results were disclosed regarding the serotypes in any of these events. Current reporting requirements to OIE should be expanded to include serotype analysis of VEE to assist in time-sensitive threat assessments.
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