MARBURG VIRUS Incubation: Symptoms in humans:

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Augusta Andrews
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3 MARBURG VIRUS Incubation: 5 to 10 days (Source: CDC) Symptoms in humans: Disease s onset is sudden and is marked by fever, chills, headache, and myalgia. Around the 5th day after onset of symptoms, a maculopapular rash, most prominent on the trunk (chest, back, stomach), may occur. Nausea, vomiting, chest pain, a sore throat, abdominal pain, and diarrhea then may appear. Symptoms become increasingly severe and may include jaundice, inflammation of the pancreas, severe weight loss, delirium, shock, liver failure, massive hemorrhage, and multi-organ dysfunction.

4 MARBURG VIRUS Symptoms in nonhumans primates: No data available on any clinical signs of infection in the green monkeys that were the source of human infection in Experimentally infected vervet, rhesus or squirrel monkeys are highly susceptible to the virus. After a 2-6 days incubation, monkeys stay apathic, stop eating and drinking, had fever, and in some rhesus monkeys petechiae were observed. Within one to two days, monkeys have severe diarrhea and hemorrhages. Lesions are characterized by focal necrosis, especially in the liver. Hemorrhages were seen in parenchymatous tissues of the lungs, liver and spleen. MARBURG VIRUS Transmission Just how the animal host first transmits Marburg virus to humans is unknown. However, humans who become ill with Marburg hemorrhagic fever may spread the virus to other people. Persons who have handled infected monkeys and have come in direct contact with their fluids or cell cultures, have become infected. Spread of the virus between humans has occurred in a setting of close contact, often in a hospital. Droplets of body fluids, or direct contact with persons, equipment, or other objects contaminated with infectious blood or tissues are all highly suspect as sources of disease. (Source: CDC)

5 MARBURG VIRUS Risk factors and seroprevalence: Following the gold mine outbreak near Durba in , 15 (2%) of 912 participants in a general village antibody survey were positive for Marburg IgG antibody. Thirteen (87%) of these 15 were men who worked in the local gold mines. Working as a miner (odds ratio [OR] 13.9, 95% confidence interval [CI] 3.1 to 62.1) and receiving injections (OR 7.4, 95% CI 1.6 to 33.2) were associated with a positive antibody result. The preponderance of antibody in male miners without obvious evidence for person-to-person transmission suggests that the local mines are a site of primary infection with Marburg virus, most likely through exposure to the primary zoonotic reservoir

6 EBOLA Virus Outbreak Bumba, Zaire 1976

11 Ebola Hemorrhagic Fever, Africa Uganda (425/53%) Ivory Coast 1994 (1) Gabon 1994 (49/59%) 1996 (31/68%) 1996 (60/75%) (60/83%) Congo 2002 (39/59%) 2003 (143/89%) South Africa, 1996 (2/50%) Sudan 1976 (284/53%), 1979 (34/65%) Zaire/Dem. Rep. Congo 1976 (318/88%), 1977 (1), 1995 (316/81%) EBOLA VIRUS Incubation: 2 to 21 days Symptoms: Ebola is often characterized by the sudden onset of fever, weakness, muscle pain, headache and sore throat. This is followed by vomiting, diarrhea, rash, limited kidney and liver functions, and both internal and external bleeding. (Source: WHO)

13 EBOLA outbreak Kikwit, 1995 Uganda, 2000

16 EBOLA VIRUS Transmission The Ebola virus is transmitted by direct contact with the blood, secretions, organs or semen of infected persons. Transmission through semen may occur up to seven weeks after clinical recovery. Transmission of the Ebola virus has also occurred by handling ill or dead infected chimpanzees, as was documented in Côte d'ivoire and Gabon. Health care workers have frequently been infected while attending patients. In the 1976 epidemic in Zaire, every Ebola case caused by contaminated syringes and needles died. (Source: WHO)

17 Ebola hemorrhagic fever, Kikwit, Zaire, 1995 transmission pattern P A T T E R N Total cases = 316 Total deaths = 245 (77%) Kikwit 2 Hospital Kikwit General Hospital January February March April May June International Notification early May July

18 A medical attendant helps a suspected Ebola case victim. (Sayyid Azim, AP) Outbreaks of Ebola hemorrhagic fever Country Year of No. human cases / Comments occurrence case-fatality rate Zaire(currently / 88% Democratic / not available Rep. of Congo) / 81% Sudan / 53% / 65% England / 0% single needle-stick case in laboratory Philippines Ebola-Reston in monkeys 1996 Ebola-Reston in monkeys USA Ebola-Reston in monkeys 1996 Ebola-Reston in monkeys Italy 1992 Ebola-Reston in monkeys Côte d'ivoire / 0% Also cases in chimpanzees Gabon / 63% / 57% South Africa / 50% initial case from Gabon Uganda / 53% Gabon /83% Congo /59% /89%

19 EBOLA Virus Outbreaks Africa

21 Pierre Rollin, CDC EBOLA VIRUS Natural Reservoir The natural reservoir of the Ebola virus seems to reside in the rain forests of Africa. Not yet identified. Different hypotheses developed to try to explain the origin of Ebola outbreaks. Initially, rodents were suspected, as for Lassa fever whose reservoir is a wild rodent (Mastomys). Another hypothesis is that a plant virus may have caused the infection of vertebrates. Laboratory observation shown that bats infected experimentally with Ebola do not die, which raised speculation that these mammals may play a role in maintaining the virus in the tropical forest. (Source: WHO)

22 EBOLA VIRUS Natural Reservoir (Cont d) Although non-human primates have been the source of infection for humans, they are not thought to be the reservoir. They, like humans, are infected directly from the natural reservoir or through a chain of transmission from the natural reservoir. Extensive ecological studies are currently under way in Côte d'ivoire to identify the reservoir of Ebola. Studies to identify the reservoir of Marburg virus, a closely related filovirus are being conducted in the Democratic Republic of the Congo. (Source: WHO) 20 Suspected Ebola Cases, by exposure date, Gabon 1996 Number of Cases Direct exposure to chimpanzee 0 Week 1 Week 2 Week 3 Week Jan Feb Feb Feb.

26 EBOLA-RESTON VIRUS 1989: October 2: 100 cynomolgus monkeys (Macaca fascicularis) flown from Manila, (The Philippines) through Amsterdam to New York and then taken by truck to Reston, Virginia. Received on 10/4/89 and quarantine in room F. At that time there were about 500 cynomolgus monkeys in the facility. Mortality in room F was found to be higher than normal for the first few weeks. November 10, 1989: 2 dead monkeys and two killed monkeys showed signs of SHF : splenomegaly, enlarged kidneys, sporadic organ hemorrhages. High SLD levels. November 16: SHF virus isolated November 27: Observation of a filovirus by E.M. Isolates of EBO and SHF made from monkeys from rooms F and H. 12 monkeys in two of the 12 holding rooms were found infected. November 28: importation of monkeys from the Philippines to Pennsylvania. Several unexplained deaths. Virus isolated from the liver of one of the monkeys. Four humans developed antibodies but did not get sick.

27 EBOLA-RESTON VIRUS 1990: Reston Virus isolated from a shipment of monkeys from the Philippines to Texas primate research facility and to Virginia. Four humans developed antibodies but did not get sick. 1992: March 11, 1992: importation to Italy (quarantine near Sienna) of 55 monkeys from the Philippines, 3/18: one monkey anorexic, found dead 3/20. 3 more deaths between 3/24 and 4/5. 4 more deaths in April. Virus isolated from 3 monkeys and high antibody titers in one monkey. 16 persons exposed. No illness, no sero conversion. EBOLA-RESTON VIRUS 1996: March 21, 100 cynomolgus monkeys shipped to Alice, Texas via Hong-Kong and Rome. during quarantine, one monkey sick (3/27) and died (3/30). Pneumonia, liver positive for Reston virus. Another sick monkey (4/10) tested for Reston Virus (serum +). Second monkey housed in a cage at opposite end of the block of cages. No human infection identified. 1996: Ebola-Reston virus identified in a monkey export facility in the Philippines. No human infections were identified. So far about 12 known seropositive persons: 6 in the USA (Reston, Virginia) and 6 in the Philippines. None were sick.

28 EBOLA-RESTON VIRUS SYMPTOMS In non-human primates: The disease is characterized by prostration, fever, lack of appetite after an average 7 days of incubation (7-14 days). Clinical changes were subtle and difficult to detect until ~24 hours before death, when anorexia and depression became obvious, followed rapidly by shock, hypothermia, extreme lethargy and coma. Hemorrhagic lesions were very discrete in a few monkeys (rectal bleeding).

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