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Workshop Objective

The Workshop aim is to explore the causes behind the emergence of Rift Valley Fever (RVF) in the Middle East and identify the research needed to effectively prevent, control and eradicate RVF.  The workshop will seek to engage RVF experts towards mitigating RVF with focus on the three pillars of RVF control:  1) vectors of disease transmission, 2) animal health, and 3) human health.  The Workshop will examine the premise that research in these areas will generate novel ideas for an integrated approach for controlling RVF in the Middle East.

Projected Outcome

A report that identifies for each of the three pillars: (1) gaps that can be addressed by research, (2) steps that must be taken to address those gaps, and (3) establishing strategic research collaborations to close the gaps.

Why is RVF important?

Rift Valley fever (RVF) is a vector-borne zoonotic disease of domestic ruminants in Africa.  RVF was first described in 1930 in the Rift Valley of Kenya.  The disease has since occurred irregularly in Kenya every 3 to 10 years.  Egypt experienced a severe epizootic in 1977 that resulted in huge losses among the domestic animal populations and caused significant human disease.  The total morbidity in people was thought to be in the hundreds of thousands, and the resources of the hospitals in the affected areas were severely strained by the numbers of cases presented daily.  Most cases were thought to arise from mosquito bites, but many of the other human cases followed close contact with infected animals, particularly slaughter or abortion.  In September 2000, following a massive East African RVF outbreak, the disease was reported in Saudi Arabia, representing the first RVF cases identified outside Africa.

RVF generally occurs during years of unusually heavy rainfall and when localized flooding occurs.  The excessive rainfall facilitates floodwater Aedes mosquito eggs to hatch.  Aedes mosquitoes acquire the virus from feeding on infected animals, and are capable of transovarial transmission (transmission of the virus from infected female mosquitoes to offspring via eggs), so new generations of infected mosquitoes may hatch from their eggs.  This provides a durable mechanism for maintaining the virus in nature, as the eggs of these mosquitoes may survive for periods of up to several years in dry conditions.  Once livestock are infected, a wide variety of mosquito species with enhanced breeding following high rainfall may act as vectors for transmission of RVF virus (RVFV) and can spread the disease.  A different species of mosquito may prove to be the predominant vector in separate regions.  In addition, it is possible that other biting insects can transmit RVFV.

RVF is most severe in sheep, goats and cattle.  Young animals, such as lambs and calves are considered the most susceptible.  Microscopically, hepatic necrosis is the most obvious lesion of RVF in both animals and humans. The acute form is most common in young animals where it causes high mortality.  Abortion is often the only sign seen in adults.  Although older non-pregnant animals are susceptible to infection, they are more resistant to clinical disease. There is considerable variation in the susceptibility of animals to different RVF genotypes.  Animal breeds that are exotic to Africa or are from areas where RVF is not endemic tend to be more susceptible.  Vaccination of livestock in infected areas is frequently not recommended because of the common practice of reusing needles, which can transfer the virus from infected animals to naïve animals.

Humans are susceptible to infection by handling or inhaling aerosols of  infected material and through transmission by mosquito vectors.  Infection of humans by vectors is a striking feature in countries with a relatively small population of animal hosts. In such areas, RVF may be recognized first in humans. RVF has caused serious disease in laboratory workers and must be handled with high level biosecurity.

Controlling RVF in endemic areas of Africa presents unique challenges:  1) Aedes mosquito reservoirs that can vertically transmit the virus to their progeny and deposit durable eggs that provide a mechanism for long term persistence; 2) domestic ruminants that can amplify the virus and increase the number of vector-borne transmissions; 3) extensive wildlife that may increase the spread of disease; and 4) significant morbidity and mortality in people who can also amplify the virus and perhaps serve as the source of infection in urban settings.  Controlling RVF if it were to reach RVF-free countries in the Middle East, Europe, or the U.S would present even greater challenges, starting with an undefined insect vector population and a significant number of susceptible livestock that could amplify the virus and increase the transmission and spread of this zoonotic disease.

Obstacles to Prevention and Control
There are several obstacles to effective prevention and control of RVF:

1. The zoonotic nature of RVFV requires countermeasures to prevent the disease in both animals and humans.

2. There are very few RVF vaccines available for animals and no licensed vaccines for people.

3. Currently, there is no specific drug available to treat RVF.  Ribavirin, which is used to treat human Lassa fever, has shown some promise as an antiviral drug.  Experimental treatments such as interferon and convalescent-phase plasma show some promise against RVF.  However, the Egyptian strain of RVFV appears to be not only more virulent, but also to be resistant to interferon.

4. RVFV has a cryptic cycle that is not fully understood.  Unusually high precipitation has a correlation with outbreaks but does not totally explain them.  Vector competence and disease transmission capability needs further characterization.  Interepidemic infection has been documented in domestic livestock, humans, and wild life.

5. Current surveillance systems in endemic areas need to be improved.  The recent spread of virus to the Arabian Peninsula raises the possibility of RVF spread to other parts of Asia, Europe, and North America.  There is currently a lack of a coordinated surveillance effort for RVFV in Africa.  The primary target should be cattle, sheep and goats. Where applicable, this needs to be extended to include the role of vectors and other possible intermediate hosts like rodents and amphibia.

6. At present, there is no rapid, pen-side or field-based diagnostic test for RVFV.  The safe handling of RVFV infected samples under field conditions is a concern.  Diagnosis of the disease is conducted in contained laboratory settings by traditional techniques of virus isolation and serological methods.  RT-PCR is highly effective for diagnosis or for confirmation, but has not been field-tested.  Delay in diagnosis could allow sufficient time in most instances for the disease to be carried away from its point of first appearance, and begin a wider range of infectivity.  IgM antibody determination is also valuable in monitoring spread of the virus in domestic livestock since it appears at the cessation of viremia and continues to indicate recent infection for several weeks.

7. As was the case with the introduction of West Nile virus in North America, the probability of early detection and rapid response of control measures if RVFV is introduced in new areas is low.  Veterinarians in Africa and the Middle East are well accustomed to the clinical signs of RVF, but this is not the case in RVF-free countries where it would not be unreasonable to expect several week delay between the first index case of the disease and a positive diagnosis.

8. Once RVFV has been diagnosed, the ability to handle and transport samples becomes restricted.  RVFV should be handled under high containment, and the numbers of compliant laboratories available to perform studies are limited.  Facilities permit this agent to be handled under BSL-3 conditions in East Africa.  In North America, the agent may be handled under BSL-3Ag conditions provided lab workers have been vaccinated and have a viral neutralization antibody titer of at least 1/40.  In the absence of these parameters, BSL-4 conditions may be required.  .

9. An additional problem associated with the inability to vaccinate field workers is the handling and disposal of carcasses.  Moreover, any livestock vaccination program incorporating a live, attenuated animal vaccine will require precautions against accidental exposure of the field workers to that vaccine.  It is reasonable to expect this will occur, and it would be prudent to employ a MLV animal vaccine strain known to be safe in people.

10. During an outbreak of RVFV in endemic areas, there is no organized system for inspecting cargo ships and airplanes for the presence of potentially infected mosquitoes. This would be particularly problematic late in the outbreak when Culex mosquitoes are common vectors, because many of these mosquitoes are prone to infesting indoor spaces.

11. Were RVFV to be introduced to the United States or another susceptible country, the response would likely require veterinary intervention (quarantine, vaccination, and herd management) and vector control. Currently, vector control assets are usually local and not every locality can do emergency vector control in a rapid manner. The only national resources are private contractors (e.g., Clarke Mosquito Control) and the U.S. Air Force, both of which require considerable lead time for response.