UPDATE--ZAIRE EBOLA OUTBREAK CDC has received reports from the Government of Zaire and the World Health Organization (WHO) of illness consistent with viral hemorrhagic fever in Kikwit, Zaire. Laboratory tests performed at CDC confirms the presence of Ebola infection in specimens from some of the ill persons in Kikwit. The strain isolated is closely related to the strain that caused Ebola disease in Zaire in 1976. The number of cases and fatalities are unknown. There have been reports of possible viral hemorrhagic fever in other locations outside Kikwit, however, these reports have not been substantiated. Three CDC investigators are in route to Zaire to participate as members of the WHO and government of Zaire team investigating the outbreak. At present, CDC believes the potential for introduction of Ebola outside of Zaire is low. The impacted area is remote and infrequently visited, and there is no direct air service between the United States and Zaire. However, public health officials and clinicians should be aware of the signs and symptoms of viral hemorrhagic fever, should question persons with suspected viral hemorrhagic fever about recent travel to Africa and should assure proper isolation if Ebola infection is suspected and contact local/state health officials. Ebola disease is usually characterized by the sudden onset of fever, malaise, myalgia, and headache followed by vomiting and diarrhea. Persons infected with the virus may suffer massive internal hemorrhaging which may lead to severe organ failure. Transmission usually occurs by direct contact with infected blood or other bodily secretions. Transmission in hospitals and other health care settings due to contaminated needles and syringes has also been documented. Ebola disease was first recognized in Sudan and Zaire in 1976. In those outbreaks over 600 people became ill and over 400 people died. A second outbreak also occurred in Sudan in 1979. In 1989, an episode involving the importation of non-human primates with a strain of Ebola, not thought to produce illness in humans, occurred in suburban Washington, D.C. In 1995, a case of Ebola disease was documented in a primate researcher working in Cote D'Ivoire. For updated information on the outbreak contact: Thomas Prentiss, 9-011-41-22-791-3221, or Christopher Powell, 9-011-41-22-791-2888 at the World Health Organization, Geneva, Switzerland ============================================================================== DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service Centers for Disease Control and Prevention (CDC) Atlanta, Georgia 30333 In reply, address CDC May 12, 1995 Refer to: NCID:DQ ADVISORY MEMORANDUM No. 111 SUBJECT: Ebola Virus Hemorrhagic Fever - Zaire The Government of Zaire and the World Health Organization have reported an unusual outbreak of Ebola virus hemorrhagic fever in Kikwit, (approximately 250 miles southeast of Kinshasa) and the surrounding areas within Bandundu Province, Zaire. The incubation period (time before symptoms appear) for Ebola virus hemorrhagic fever may range from 2-21 days. The average is approximately 1 week. The illness is characterized by an abrupt onset of fever and headache. Continued fever, headache, general malaise, muscle aches, joint pain, and sore throat are commonly followed by vomiting, diarrhea and abdominal pain. A transient, measles-like skin rash, that subsequently becomes scaly, often appears at the end of the first week of illness. Persons infected with the virus may sufferinternal hemorrhaging, severe organ failure and death. The disease is primarily transmitted by contaminated injections and close personal contact with severely ill patients. Transmission usually occurs by direct contact with infected blood, secretions, organs or semen. Otherwise, the risk of infection is believed to be very low. Persons in the incubation period are not considered to be a significant risk to those around them. Travelers to Zaire are at low risk of acquiring the disease under normal circumstances. To eliminate the risks, travelers should avoid the Ebola virus areas described above. Travelers in Zaire should contact the U.S. Embassy for further information after arrival in Kinshasa. For future updates of this advisory, you may call CDC International Travelers' Voice Information Service at (404)332- 4559 press 1, then press 4, and listen for the outbreak menu for Zaire or you may call the CDC Fax Information Service at (404) 332-4565 and request document #221009. All recipient health departments, travel agencies, airlines, and shipping companies should notify prospective travelers of the recommendations in this advisory. Brian Mahy, Ph.D. Charles R. McCance Director Director Division of Viral aDivision of Quarantine Rickettsial DiseasNational Center for National Center for Infectious Diseases Infectious Diseases ============================================================================== EBOLA VIRUS HEMORRHAGIC FEVER: GENERAL INFORMATION What are viral hemorrhagic fevers? Viral hemorrhagic fevers are a group of diseases caused by viruses from four distinct families of viruses: filoviruses, arenaviruses, flaviviruses, and bunyaviruses. The usual hosts for most of these viruses are rodents or arthropods (such as ticks and mosquitoes). In some cases, such as Ebola virus, the natural host for the virus is unknown. All forms of viral hemorrhagic fever begin with fever and muscle aches. Depending on the particular virus, the disease can progress until the patient becomes very ill with respiratory problems, severe bleeding, kidney problems, and shock. The severity of viral hemorrhagic fever can range from a relatively mild illness to death. What is Ebola virus? The Ebola virus is a member of a family of RNA viruses known as filoviruses. When magnified several thousand times by an electron microscope, these viruses have the appearance of long filaments or threads. Ebola virus was discovered in 1976 and was named for a river in Zaire, Africa, where it was first detected. Ebola virus hemorrhagic fever: How common is it? Until recently, only three outbreaks of Ebola hemorrhagic fever among people had been reported. The first two outbreaks were in 1976: one in Zaire and one in western Sudan. These were large outbreaks, resulting in more than 550 cases and 340 deaths. The third outbreak, in 1979 in Sudan, was smaller, with 34 cases and 22 fatalities. During each of these outbreaks, a majority of cases occurred in hospital settings under the challenging conditions of the developing world. These conditions, including a lack of adequate medical supplies and the frequent reusing of needles and syringes, played a major role in the spread of disease. The outbreaks were quickly controlled when appropriate medical supplies and equipment were made available and quarantine procedures were used. The source of the Ebola virus in nature remains unknown. In an attempt to identify the source, investigators tested thousands of specimens from animals captured near the outbreak areas, but their efforts were unsuccessful. Monkeys, like humans, appear to be susceptible to infection and may serve as a source of virus if infected. What do we know about the recent outbreak of Ebola virus infection? The recent Ebola virus outbreak is centered in Kikwit, Zaire. (Kikwit is a city of 400,000 located 400 kilometers east of Kinshasa, the capital of Zaire.) The outbreak appears to have started with a patient who had surgery in Kikwit on April 10, 1995. Members of the surgical team then developed symptoms similar to those of a viral hemorrhagic fever disease. Ebola hemorrhagic fever was suspected by a Belgium physician who reported the disease to the Zairian government. At the request of Zairian health officials, medical teams from CDC, the World Health Organization, and from Belgium, France, and South Africa are collaborating to investigate and control the outbreak in Zaire. What are the symptoms of Ebola hemorrhagic fever? Symptoms of Ebola hemorrhagic fever begin 4 to 16 days after infection. Persons develop fever, chills, headaches, muscle aches, and loss of appetite. As the disease progresses, vomiting, diarrhea, abdominal pain, sore throat, and chest pain can occur. The blood fails to clot and patients may bleed from injection sites as well as into the gastrointestinal tract, skin, and internal organs. How is the Ebola virus spread from person to person? Ebola virus is spread through close personal contact with a person who is very ill with the disease. In previous outbreaks, person-to-person spread frequently occurred among hospital care workers or family members who were caring for an ill person infected with Ebola virus. Transmission of the virus has also occurred as a result of hypodermic needles being reused in the treatment of patients. Reusing needles is a common practice in developing countries, such as Zaire and Sudan, where the health care system is underfinanced. Medical facilities in the United States do not reuse needles. Ebola virus can also be spread from person to person through sexual contact. Close personal contact with persons who are infected but show no signs of active disease is very unlikely to result in infection. Patients who have recovered from an illness caused by Ebola virus do not pose a serious risk for spreading the infection. However, the virus may be present in the genital secres of such persons for a brief period after their recovery, and therefore it is possible they can spread the virus through sexual contact. How is Ebola hemorrhagic fever diagnosed? A diagnosis is made by detection of Ebola antigens, antibody, or genetic material, or by culture of the virus from these sources. Diagnostic tests are usually performed on clinical specimens that have been treated to inactivate (kill) the virus. Research on Ebola virus must be done in a special high-containment laboratory to protect scientists working with infected tissues. How will health officials control the outbreak? Previous outbreaks of Ebola hemorrhagic fever have been limited. These outbreaks were successfully controlled through the isolation of sick persons in a place requiring the wearing of mask, gown, and gloves; careful sterilization of needles and syringes; and proper disposal of waste and corpses. How do hospital personnel isolate an ill person? Hospital personnel isolate ill persons through a method called "barrier technique." Barrier technique includes the following actions: 1) doctors and nurses wear gowns, mask, gloves, and goggles when caring for patients; 2) the patient's visitors are restricted; 3) disposable materials are removed from the room and burned after use; 4) all reusable materials are sterilized before reuse; and 5) since the virus is easily destroyed by disinfectants, all hard surfaces are cleaned with a sanitizing solution. Are persons in the United States at risk? Persons in the United States are at risk only if they have had close personal contact with patients in Zaire who are infected with Ebola virus. There are no reports that infected persons have left the country of Zaire. The Zairian government has quarantined all persons in the affected areas and restrictemovement of persons in and out of these areas. Any persons who wish to travel to Zaire are encouraged to contact the U.S. State Department (202-647-5225) for travel advisories. What is CDC's role in the outbreak investigation? CDC has sent three medical scientists to Zaire to assist with the investigation. They will provide advice and assistance in helping to control the outbreak and prevent additional cases, collect specimens for diagnostic testing, study the cnical course of the disease in ill persons, and look for others who may have been in contact with the infected individuals. They will also be instruct the hospital staff in Zaire about how to limit the spread of the disease. Efforts will also made to find the source of the infection. CDC also has a role in educating the U.S. public about this outbreak and about the potential threat of emerging infectious diseases. For the next several days, CDC will issue press releases and will inform the state health departments about any updates on the disease outbreak Zaire. ============================================================================== Press Release WHO/36 20 May 1995 EBOLA EPIDEMIC IN ZAIRE : UPDATE ON FIGURES The international Committee on Scientific and Technical Coordination, supported by the team of experts of the World Health Organization (WHO) in Zaire, informed today that the number of cases of Ebola haemorrhagic fever reported from the beginning of the epidemic is now 128, including 97 deaths, which represents an increase of 4 cases and 8 deaths, compared to the previous update issued yesterday. Epidemic control continues in Kikwit with the same two major strategies: epidemiological surveillance to identify all cases and deaths in order to isolate patients and bury the dead under safe conditions; and improvement of conditions at the Kikwit General Hospital, in order to enhance patients' confidence so that they will show up to hospital for care. At the same time, a team from WHO and the Government of Sweden has started medium and long term needs assessments in the region of Bandudu in order to strengthen and sustain the health infrastructure and surveillance activities. On 19 May 1995, as a preliminary medium term activity, 52 physicians from all hospitals and health facilities in the region, who are currently participating in surveillance and case finding activities, were provided with one day training in surveillance, patient management and control measures, such as patients isolation. A new update on the Ebola haemorrhagic fever epidemic is expected to be published tomorrow, Sunday 21 May 1995. ============================================================================== Press Release WHO/32 17 May 1995 EBOLA HAEMORRHAGIC FEVER: ADVICE TO TRAVELLERS In the wake of the universal media coverage, the current outbreak of the Ebola haemorrhagic fever in south-western Zaire is raising questions of travellers' safety. Given the unlikelihood of any patient with Ebola haemorrhagic fever travelling from the country, the World Health Organization (WHO) does not recommend that any special measures be instituted with respect to aircraft or the general travelling public arriving from Zaire. A very small number of individuals (principally health care workers and journalists) will be returning to their home countries after having been in known contact with Ebola patients in Zaire. Unless these passengers are obviously ill, no travel restrictions are required, but such persons are advised to inform health/quarantine officials at their destination of their exposure history and where they may be contacted during the incubation period of the disease. If they fall ill during this period, they should seek immediate care and notify the health/quarantine authorities of this fact. Other passengers leaving Zaire are advised to notify a doctor immediately if an illness develops during a period of three weeks from the departure date. In particular, any fever should be reported at once and the physician informed that the patient has travelled from Zaire. The incubation period for Ebola haemorrhagic fever is up to 21 days. Persons with Ebola become infectious for others only when they are extremely ill and are already haemorrhaging (bleeding). It is highly unlikely that such persons would try to travel on an international flight, and unlikely that they would be permitted to board if they did try. If on board, they would represent a hazard to members of the crew and any passengers who had direct contact with the patient's blood. Such passengers should be placed as far as is practical from other passengers and crew. Aircrews, as a routine, should advise ground staff at their destination if they have severely ill passengers on board. Health and/or quarantine authorities should arrange for the isolation of these passengers for initial clinical screening for Ebola. Passengers and crew who had close prolonged contact with the patient (e.g. passengers sitting in an adjoining seat but not across the aisle or in front or behind unless specific contact occurred, or crew providing care) should be advised of the hazard and, on arrival, be placed under surveillance (e.g. active contact maintained by telephone or visit). Others in the aircraft should be advised of the hazard and told to contact a physician if they become ill. ============================================================================== EBOLA HAEMORRHAGIC FEVER Clinical picture: A severe viral illness, usually characterized by sudden onset with weakness, fever, muscle pain, headache and sore throat, followed by vomiting, diarrhea, rash, limited kidney and liver involvement, and both internal and external bleeding. Ebola infections end in death from 50% to nearly 90% of those clinically ill. Incubation period is 2 to 21 days. Diagnosis is by specialized laboratory tests (not commercially available) to detect specific antigen or antibody and/or isolation of the virus. Laboratory studies present an extreme biohazard and should be conducted only under high containment conditions. Therapy: No specific treatment or vaccine exists. Severe cases require intensive supportive care. Patients are frequently dehydrated and need intravenous fluids. Occurrence and reservoir: Ebola disease was first recognized in the western equatorial province of the Sudan and the nearby region of Zaire in 1976; a second outbreak occurred in the same area in Sudan in 1979. The reservoir of Ebola is unknown despite extensive studies. Ebola-related filoviruses were isolated from cynomolgus monkeys (Macacca fascicularis) imported into the United States of America from the Philippines in 1989; many of these monkeys died, and at least four persons were infected, although none suffered clinical illness. Transmission of Ebola virus is person-to-person by direct contact with infected blood, secretions, organs or semen. Hospital acquired infections have been frequent, and many health care workers have been infected while attending patients. In the 1976 Zairean epidemic all Ebola cases linked to contaminated syringes and needles died. Transmission through semen may occur up to 7 weeks after clinical recovery as has been the case with Marburg haemorrhagic fever. Containment: Suspected patients should be isolated from other patients. Strict barrier nursing techniques should be practised. All hospital personnel should be briefed on the nature of the disease and the routes of transmission. Particular emphasis should be placed on high risk nursing procedures such as placing intravenous lines, handling of blood and secretions, catheters and suction. Hospital staff should have individual gowns, gloves and masks. Gloves and masks must not be reused unless disinfected. Fatal cases should be promptly buried or cremated. Contacts: As the primary mode of person-to-person transmission is contact with contaminated blood, secretion or body fluids, any person who has had close physical contact with patients should be put under strict surveillance (twice daily body temperature checks; in case of temperature >38.3 C (101 F), hospitalize immediately in strict isolation). Casual contacts should be placed on alert and asked to report any fever. All surveillance should be continued for three weeks after the date of the last contact. Hospital personnel who come into close contact with patients or contaminated materials without barrier nursing attire must be considered exposed and put under close, supervised surveillance. ============================================================================== DR. FREDERICK A. MURPHY TALKS ABOUT THE EBOLA VIRUS An Interview by Sean Henahan, Access Excellence The book "The Hot Zone" and the film "Outbreak" have seized the public's imagination and brought into focus many issues regarding the very real threats posed by new and emerging diseases. In this interview we talk with Frederick A. Murphy, D.V.M., Ph.D., Dean of School of Veterinary Medicine, UC Davis. At the time of the 'Reston incident', Dr. Murphy was the director of the National Center for Infectious Diseases at the CDC in Atlanta. Dr. Murphy is considered one of the world authorities on viruses. He was the first one to look at Ebola virus 'face-to-face' in the electron microscope. Dr. Murphy appears in "The Hot Zone" and his now famous photo of the Ebola virus appears in the film "Outbreak". Note: Dr. Murphy has also provided an extensive bibliography and three excellent electron micrographs to accompany this interview. Q: The book "The Hot Zone" and more recently the film "Outbreak" have brought public attention to the reality of emerging viruses and potentially disastrous epidemics. It can be difficult to tell fact from fiction with these kind of sources. I'd like to ask some questions gathered from high school science teachers and students all over the country to clarify some of the issues raised by this book and this movie. A: The public response to the book and the film has been phenomenal. Half of the posts for a virology conference on the Internet I look at are about the Ebola virus. I myself have had innumerable calls from the press and other media people. By the way, I want to say hello to the Access Excellence people and say I had a great time down at Genentech last summer when I spoke on the subject of new and emerging diseases. Q: Please explain how Ebola and the other filoviruses are classified and how they are related to other known viruses? A: The viruses are classified in the family 'Filoviridae', with one genus, 'Filovirus'. There are four known viruses. We have Marburg virus and three Ebola viruses: Zaire, Sudan and Reston. Marburg and Ebola are distinguished by their length when purified. In the unpurified state you get all different lengths of these worm-like virions. When they are purified, the infectivity is associated with a particular particle length, which is slightly different between the Marburg and Ebola, but all of the Ebola viruses are the same length. Q: Considering how similar the Ebola viruses are, how are they differentiated? A: They are very close. First of all, there is a very small serologic difference among the Ebola viruses which can help distinguish them. Second, there are sequence differences which can be determined using the tools of molecular biology. Q: What have we learned about the Ebola genome, and what remains to be learned? A: Ebola Zaire has been completely sequenced and Ebola Reston is nearly completed. The gene order of these viruses reaffirms their independence as a family. Also, some ancient conserved sequences along with the gene order, i.e. the layout of the genes along the RNA molecule, put the family 'Filoviridae' into an order, the only order in virology, 'Mononegavirales' This emphasizes the ancient phylogenetic connection between three families- 'Filoviridae', 'Paramyxoviridae' (measles, mumps) and 'Rhabdoviridae' (rabies). There is no connection with HIV. Q: Let's talk about the pathogenicity of Ebola. How does Ebola virus infect humans? A: In Zaire and Sudan, Ebola virus was spread by close contact and dirty needles. The center of the epidemic in Zaire involved a missionary hospital where needles and syringes were re-used without sterilization. Most of the staff of that hospital got sick and died. There were secondary cases involving people taking care of sick people or preparing bodies for burial, but the virus essentially shut down after that epidemic peaked. There is something of a misconception that Ebola virus can infect just about any cell. In fact, the virus has a very specific tropism for liver cells and cells of the reticuloendothelial system, e.g. macrophages. Massive destruction of the liver is a hallmark feature of Ebola Zaire, Ebola Sudan, and Ebola Reston (the latter in monkeys only). Q: Ebola Zaire is said to kill nine of ten people infected. What about the surviving one person? Is anything known about natural resistance to this virus? A: Starting with Marburg in 1967, there was one fellow who tested positive for the virus 30 days post-infection. In fact the virus was detected in his semen, and there was a case of sexual transmission in that circumstance. Another patient had virus in the vitreous of his eye for more than 30 days. But eventually the virus died out within these people without killing them. Ebola too is not persistently carried in the blood and appears to be self limiting in the surviving patient. Q: Given that there are some signs of natural immunity to Marburg and Ebola Zaire, and that the monkey workers were not killed after exposure to Ebola Reston, does this give us any possible approaches to vaccine development? Both the measles and rubella vaccines were based on attenuated viruses. A: No, I don't think so. I don't think we would know how to select a stable, safe attenuated virus. The kind of research needed to develop a modified live virus vaccine simply could not be done given the scope of the problem. That is, you only have a few people working in labs who would need to be vaccinated, and you might want a vaccine stockpile in the event of an epidemic, but these are not the scale of circumstances where we could afford to develop a vaccine. A killed vaccine is much simpler to develop, but so far this has not worked with Ebola virus. Q: On Oct 13, 1976 you prepared a specimen from an African patient with hemorrhagic fever and suddenly realized it might be deadly serious. Can you tell us what you were thinking at that time? A: When I put the specimen in the electron microscope, I was sure it was Marburg. I had worked on Marburg in 1967 and 1968 and had done a project on experimental Marburg infection in monkeys. The specimen had come back from Zaire to the CDC in Atlanta in less than optimal condition, with the tubes in the box broken. Anyone else would have taken a look and put the whole box in the autoclave, but Dr. Patricia Webb, wearing gloves, gown and mask, squeezed a few drops of fluid out of the cotton surrounding the broken tubes. That was the material the virus was isolated from. It was placed in tissue culture (monkey kidney cells) for a couple of days then I got a drop of the tissue culture fluid and prepared a specimen for the electron microscope. When I saw what I was sure was Marburg, I shut the electron microscope down and went back to the room in which I had prepared the specimen. This was in the days when hoods were a lot more primitive. I "cloroxed the hell" out of the place where I had done the preparation and carried my discard pan with gown and gloves etc. to the autoclave and ran it. Then I went back to the microscope and called Karl Johnson and Patricia Webb to take a look. I shot a cassette of pictures and with wet negatives, not good for the enlarger and I made prints which were available within minutes. I carried these dripping prints to the office of the Director of the CDC. It was very dramatic. Q: Then later when Fort Detrick called and said they thought they had found Ebola in Virginia, what was your reaction? A: The way it is stated in "The Hot Zone", General Russell suggested I didn't believe him. In fact, I took it very seriously. General Russell himself had enough experience to recognize Ebola when he saw it. With Marburg 67, it was monkeys that brought the virus to Europe. In 1976 we had no idea where the virus came from, so when he said he had Ebola in monkeys I sure believed him. We went to Fort Detrick the next day. Q: There are a number of issues concerning the response to an epidemic raised by both "The Hot Zone" and "Outbreak". How well did these describe the interaction of the various agencies? A: The movie Outbreak created some false impressions. The law in our country gives the responsibility for epidemic management to state health departments, with these agencies calling CDC when need help. CDC has no authority to go into a state except by invitation. The Army could be called in by a state health department, but to my knowledge this never has happened. In the Reston incident, the Virginia Health department and the CDC took over the human health side of the episode and the Army, at the request of the monkey import company, took over the animal side. It turned out after lots of surveillance of animal caretakers and their families that there was no human disease, but there was plenty of monkey disease. The Army's role involved depopulating the monkey colony. So the movie Outbreak, where the Army takes over, is rather fictional. Q: Has the Reston incident changed the way monkeys are imported and housed? A: There were a series of CDC investigations after the Reston episode. There walso a complete embargo on the importation of monkeys for about a year. The CDC then relicensed importers, denying licenses to those that did not have propfacilities and staff training. So I would say there has been significant improvement in this area. Countries that used to export monkeys are also getting out of that business. primarily for species preservation reasons. The use of captive bred monkeys is absolutely the trend. The goal is or complete reliance on domestic breeding. We have to stretch the definition a bit, since there is a huge captive breeding colony on a small Caribbean island. Q: Did anyone every figure out how an African Ebola virus ended up in a monkey from the Philippines? A: No. That's a very good question. We still have no idea where Ebola lives in nature. It was not possible to do field studies in the Philippines because of a civil war going on in the area they came from. Some studies in Africa tried to trace Marburg and Ebola, but nothing has ever been found. Q: Are budget cuts affecting the ability of the CDC and other agencies to respond to epidemic outbreaks? A: Yes. The Army program at USAMRID has been cut quite a bit. Over the past few years the CDC's programs for dealing with infectious diseases have been nibbled to death by inflation. The budgets are the same in today's dollars as they were 12 years ago. In effect these programs have lost half of their purchasing power, while at the same we've seen an explosion in AIDS and other infectious diseases. Q: Such as Hantavirus? A: Yes, hantavirus is a good example. The same people from CDC and the Army who worked on the new Hantavirus outbreak previously worked on Ebola. It is a small, wonderful group of dedicated people. They really have had their budgets whacked. And then with the emergence of one disease problem after another, this has really stretched them beyond the breaking point. Q: Can you give us an update on the Hantavirus situation? A: It is amazing how quickly the virus was characterized after the first outbreak in the Four Corners area. The virus is transmitted by breathing dried dust that contains the virus (from the dried feces, urine and saliva of the mouse vector, 'Peromyscus maniculatus'). The virus could not be grown, so everything was done by molecular biological means. The first clue came with the observation of some cross serology with known hantaviruses. Everything else was done by PCR and partial sequencing. Six months later they were able to make an isolate. Since then four different variants of the virus have been isolated from more than 100 people. It still has a mortality rate above 50% and has been seen from California to the East Coast and Florida. It is incredible that this set of variant viruses was present all along and no one knew it. Although we know the vector, we also know that controlling this vector, mice, is virtually impossible. We have a similar problem now in California, with all the rains. The mosquitoes that carry Western equine encephalitis and St. Louis encephalitis are resistant to virtually every licensed insecticide. We could have a re-emergence of these virus diseases this summer. The most important mosquito-born disease in the world today is dengue. This disease is emerging now in all the big cities of the Caribbean and tropical and sub-tropical America. If you get lots of dengue and multiple serotypes in an area, you get dengue hemorrhagic fever. Uncomplicated dengue infection, called breakbone fever, is like influenza, with all people recovering. But dengue hemorrhagic fever, usually seen in children, is deadly. Symptoms include fever, shock, hemorrhaging from the nose and mouth, respiratory distress and, in some cases, death. Q: Back to the CDC. What do public health agencies need in order to fight epidemics? A: The things they need are hard to come by. The National Academy of Sciences, the Institute of Medicine and the CDC have published plans on what is needed to control new and emerging diseases better. The plans focuses on better surveillance, better laboratory diagnostics, better communication and better education. The plans are very good, but the timing is terrible, since budgets are so tight, and from what I read in the papers, budgets will get much worse. Q: There have been complaints at the vast inaccuracies and dubious details in the film Outbreak. What did you think of this film? A: I did see the movie. In fact, in return for the use of the electron micrographs of the virus, Warner Bros. gave us tickets to the premiere in Sacramento. I thought the early scenes in the biosafety level 1,2,3, and 4 labs looked pretty accurate. After that it became fictional, and I enjoyed it as fiction. We know a virus can't kill someone in an hour. The making of the antisera in a day was ludicrous. I think all bug movies have a problem, since once they unleash the bug, there is the problem of resolving the crisis. Like in the film, 'The Andromeda Strain', the only way to resolve the story was to have the bug mutate to become harmless. The real world is not so simple. Fourteen years into the AIDS epidemic and we still don't have a vaccine or decent drugs. Q: The CDC is one of two places in the world with remaining specimens of smallpox virus. Both the CDC specimens and the Russian specimens were scheduled for destruction, but have gained a reprieve. Should they be saved? A: The collections of smallpox specimens at these places are fairly large. CDC has about 500 strains of the virus. It is highly contained in a freezer that is never opened. The WHO also visited the Russian facility and certifiits safety. I was originally in favor of the destruction of these specimens. This was for political reasons, rather than scientific ones. I thought publicity surrounding its destruction would remind people that we had done something very good. However, within the last two years several different strains of the smallpox virus have been completely sequenced. Some really interesting genes have been found, which may contribute to the understanding of the pathogenicity and natural history of other viruses. So the current consensus is that these kinds of genes must be preserved and studied. Q: Last question. Any advice for some one considering a career in virology? A: There are several kinds of virologists. One kind of virologist is a molecular biologist who studies the nature of the virus and how it works. That is the world of molecular biology and cell biology. Virology is also an infectious disease science in the hands of physicians and veterinarians who take specialty training. Virology also interfaces with other areas of biology that have to do with how viruses are transmitted, such as entomology and mammology. The field of virology also includes the whole world of public health and preventive medicine. The starting point for anyone interested in virology is the undergraduate biology major. Then there is a fork in the road at which the person chooses to seek a degree from a medical school or veterinary school or to enter a Ph.D program in virology per se. Either way you go, I can say "it's a wonderful life". ============================================================================== DISEASE FIGHTS BACK Excerpted from The Economist, May 20, 1995. This is an excellent article which discusses viruses' mounting resistance to antibiotics. The complete article can be found on page 15 of the May 20, 1995 issue of The Economist. Excerpts follow. _______________________________________________________________ Ebola is a terrifying illness. It kills quickly. Nine in every ten of those who become infected die, and it is an especially hideous death. Thanks to its speed and gruesomeness, this virus has commanded front-page headlines all over the world in recent days. Sleeping sickness -- which can be just as deadly and whose spread across large parts of Zaire is virtually unchecked -- has commanded no such attention. This is not so surprising: Ebola is new and untreatable, sleeping sickness is old and treatable -- merely untreated. The outbreak of Ebola in Kikwit has so far claimed about 100 victims; sleeping sickness kills 200,000 Zairois a year.... The problem humans have with germs is that they work by rules that humans find hard to deal with, so different that before Pasteur no one knew what they were. Germs are quick; humans are slow. Germs have no thought for the future; humans plan. Germs have no technologies; humans are consummate users of tools. Most important, germs never give up. Humans do so all too readily. For centuries staphylococcus bacteria made trivial wounds fatal injuries. Then science came up with a tool to use against them: penicillin. In 1952 staphylococcus bacteria were almost 100% susceptible to penicillin, and the scourge became an irritant. By 1982, 90% of the strains had become resistant to the drug.... ============================================================================== Zaire sets checks to keep virus from Kinshasa (c) 1995 Copyright the News & Observer Publishing Co. (c) 1995 Reuter Information Service KINSHASA (May 22, 1995 - 11:30) - Zaire, whose capital has been spared by the Ebola virus, has introduced checks at unexpected spots on roads into Kinshasa to screen for the deadly disease. With the death toll topping 100, World Health Organisation spokesman said Ebola death toll passes 100; outbreak may have started as early as December. Sammy Chumfong said on Monday that the random checks replaced a failed attempt to stop all travel to the capital from the virus-stricken province of Bandundu. "The screening posts are dotted everywhere for purposes of random testing. We don't want people to know where they are, so they don't try to avoid them," he told Reuters. "There's really nothing else we can do," he said, adding: "After doing a number of tests we concluded that keeping people at the frontier (between the province and the area around the capital) was not really the solution." Medical experts in Kikwit, at the heart of the epidemic which was at first was mostly confined to doctors and nurses at Kikwit General Hospital, expect a clearer picture to emerge this week of the impact one general population. Medical teams based in Kikwit, 500 km (300 miles) from Kinshasa, have been scouring outlying villages for Ebola cases and burying bodies -- often abanded by frightened relatives. The virus, which is contracted by contact with blood or bodily fluids, kills by causing uncontrollable bleeding. There is no known vaccine or cure. It resurfaced in March when a man died of it in Kikwit hospital but the WHO, which is spearheading the fight against the disease, spoke of cases in the area as far back as December. The WHO in Geneva put the death toll by Sunday at 101 from 137 cases -- up from 97 deaths by Saturday. Kinshasa, where no cases have been reported, went to work as normal on Monday. In the bustling streets and markets, it appeared like any other Monday, but thoughts of the virus were at the back of many people's minds. Some talked about it, others joked. Graphic posters on walls, public buildings and bus stops spelled out the dangers of touching anyone showing symptoms of the disease, which can kill up to nine out of 10 victims. In Kikwit, posters were also on taxis. Trucks from Bandundu Province, which provides almost half Kinshasa's food, clattered into the capital and its markets throughout the night. Kinshasa went without fresh supplies of food last week after the authorities set up roadblocks on the main highway from Bandundu and the east, preventing trucks and travellers reaching the city. They lifted the blockade on Saturday, fearing angry scenes or worse from several thousands travellers and truck drivers marooned at a roadblock 150 km (90 miles) from the capital. The outbreak in Zaire has had repercussions throughout the region and Kenyan tourism industry officials appealed on Monday for overseas visitors not to cancel their holidays in the East African country. "We would like to tell the world there is no outbreak of this disease in Kenya at all," Colonel Joe Nguru, chief executive of the Kenya Association of Tour Operators told Reuters in the Kenyan capital Nairobi. ============================================================================== EBOLA RECOMMENDED READING LIST "Outbreak of Fear" Newsweek, May 22, 1995 "Viral hemorrhagic fever in southern Sudan and Northern Zaire" by Bowen et al., Lancet, vol. 1, pp 571-573 (1977) "Management of patients with suspected viral hemorrhagic fever," CDC-Morbidity and Mortality Weekly Report, Supp. 37/S-3, pp 1-16 (1988) "Update: Ebola-related filovirus infection in nonhuman primates and interim guidelines for handling nonhuman primates during transit and quarantine," CDC- Morbidity and Mortality Weekly Report, vol. 39, pp 22-4 & 29-30 (1990) "Biosafety in Microbiological and Biomedical Laboratories" by the CDC/NIH, HHS Publication No.CDC-1993, 3rd Edition "Epidemiologic investigation of Marburg virus disease, Southern Africa, 1975" by Conrad, et al., Am. J.Trop. Med. Hyg., vol. 27, pp 1210-1215 (1978) "Molecular biology and evolution of filoviruses" by Feldmann et al., Arch.Virol (supp), vol. 7, pp 81-100 (1993) "Association of Ebola-related Reston virus particles and antigen with tissue lesions of monkeys imported to the United States" by Geisbert et al., J. Comp. Path., vol. 106, pp 137-152 (1992) "Preliminary Report: isolation of Ebola virus from monkeys imported to USA" by Jahrling et al., Lancet, vol. 335, pp 502-05 (1990) "Isolation and partial characterization of a new virus causing acute hemorrhagic fever in Zaire" by Johnson, et al., Lancet, vol. 1, pp 569-571 (1977) "Agent of disease contracted from green monkeys" by Kissling et al., Science, vol. 160, pp 888-890 (1968) "Infectious Diseases" by Frederick A. Murphy, Avances in Virus Research, vol. 43. Pathology of Ebola virus infection" by F.A. Murphy, Ebola Virus Hemorrhagic fever (ed. by Pattyn, Elsevier/North Holland, Amsterdam), pp 37-42 (1978) "Marburg virus morphology and taxonomy" by F.A. Murphy, Ebola Virus Hemorrhagic fever (ed. by Pattyn, Elsevier/North Holland, Amsterdam), pp 61-82 (1978). "Marburg virus infection in monkeys" by Murphy et al. Lab. invest., '71, vol. 24, pp 279-291 (1971) "Filoviruses as Emerging Pathogens" by C.J. Peters et al., Seminars in Virology, vol. 5, pp 147-154 (1994) "Filoviruses" by C.J. Peters et al., Chapt.15 in Emerging Viruses (ed. by S. Morse, Oxford University Press, New York), pp 159-75 (1991) Richard Preston. Esquire. July/August 1993. "The Hot Zone." Scientific American, vol. 271, pp 114 (Nov. 1994). Richard Preston. The Hot Zone David Quammen. "You Can Run: Emerging viruses in the global village" Discover Apr 1994. "Sequence analysis of the Ebola virus genome: organization, genetic elements, and comparison with Marburg" by Sanchez et al., Virus Res., vol. 29, pp 215-240 (1993). Zinsser. MICROBIOLOGY, 20th ed. pages 1031-1033. (has a section on Ebola and about 10 references-books, journal articles, and WHO bulletins) The TV newsmagazine 48 Hrs did a show on ebola and hanta virus called "Into the Danger Zone" "The Apocalypse Bug" - May 14, 1995 on CNN