EBOLA Virus

Ebola haemorrhagic fever was first recognised in 1976, when large outbreaks occurred in southern Sudan and neighbouring northern Zaire. Person-to-person spread was common in the local hospitals, but also caused many cases in the community. Mortality rates were as high as 80-90% in some groups of patients, giving rise to extreme concern both in the original outbreaks and in case of export of the disease to non-endemic areas

Area affected	Cases identified	Deaths
Nzara, Sudan 1976	70	33
Maridi, Sudan 1976	229	117
Northern Zaire 1976	318	280
Zaire 1997	1	1
Nzara, Sudan 1979	34	0
Cote d'Ivoire 1994	1	0
Kikwit, Zaire 1995	315	244
Booue, Gabon 1996	24	17
Libreville, Gabon	3	3
Johannesburg, South Africa	2	1

Transmission during outbreaks

In the 1976 Sudan outbreaks, the staff of Maridi Hospital were severely affected, 76 of the 230 staff contracted Ebola fever, with 41 deaths. A scientist in the UK suffered severe illness, but recovered fully, after sustaining a minor inoculation injury whole studying the virus. The 1994 case in Cote d'Ivoire was in a scientist who conducted an autopsy on a wild chimpanzee found dead with signs of haemorrhagic disease. The 1995 Kikwit outbreak was thought to have occurred after the index case handled a monkey and smoked its flesh. This outbreak permitted the study of household secondary cases. All those affected had directly cared for cases of Ebola Fever, there were no identified secondary cases in household members who had no contact with the case. This suggests that airborne spread does not take place in households.

In 1989, 1990 and 1996 Ebola virus has been isolated from cynomolgus monkeys in quarantine facilities in Virginia, Texas and in Pennsylvania. These animals had been recently imported into the USA from the Philippines. Another batch of cynomolgus monkeys infected with Ebola was imported into Siena, Italy in 1992. No human clinical cases were associated with any of these outbreaks although serological evidence of asymptomatic infection was found in 15 individuals. The monkey shipments in the 1989 and 1990 incidents originated from the same handling facility in the Philippines, where the presence of the virus has also been documented.

The Ebola virus and its detection

The virus is present in high concentrations in the blood, tissue fluids and most organs of the body. It can be cultured in a variety of cells; most commonly used are monkey kidney (VERO) cells. The virus itself is a single-stranded, enveloped RNA virus, which appears to have a curled or twisted end in electron-microscope preparations. It may be sufficiently concentrated to be detectable in electron microscope studies of plasma. It can also be seen in appropriately stained tissues such as liver. Its filamentous shape is unique among viruses infecting primates, and it is classified with the similar Marburg virus in the family of filoviruses. You could put a photo from the inside front cover here

Electron micrograph of Ebola virus		Electron micrograph of Ebola virus

The virus induces an early IgM antibody response, and positive IgM ELISA tests can be expected after 4-7 days of illness. Earlier positive results may be obtained by reverse transcriptase PCR tests for viral genome, but the method is not sufficiently specific for a negative test to indicate freedom from infection.

The strains of Ebola virus isolated from Zaire, Sudan, Cote d'lvoire, Gabon, USA and Italy have been found to be distinct but morphologically identical with Marburg virus. Serological and sequencing studies suggest a close similarity between the original Ebola isolates from the 1976 and the 1995 outbreaks in Zaire. Strains from the 1996 Gabon outbreaks were almost identical to one another and closely similar to the 1976 and 1995 Zaire isolates.

Natural reservoir of Ebola virus

The natural reservoir of Ebola virus is unknown but monkeys may be a link to humans. Once successfully transmitted to humans, the Ebola virus is capable of person-to-person spread, most commonly by contact with infected blood. Virus has also been isolated from the semen of a convalescing patient. Aerosol transmission has not been described in the clinical setting. In the laboratory and other experimental settings, aerosol transmission between animals can not be entirely excluded.

The incubation period of the Ebola virus infections in the outbreaks in Africa was around 7 days with extremes of 4-16 days.

The onset of illness is abrupt with shivering and a rapid rise in temperature accompanied by severe headache, backache and muscle and joint pains. Gastro-intestinal disturbances may be a presenting feature, but more commonly commence on about the third day with anorexia, nausea, vomiting and diarrhoea. The stools are watery and sometimes contain blood and mucus. Profuse diarrhoea may continue for several days and will lead to severe dehydration unless treated.

After 3-8 days many patients develop a morbilliform rash, which persists for 4-14 days and is followed by fine desquamation. The throat and conjunctivae may be inflamed and small transparent lesions resembling tapioca granules may be present on the soft palate. Many patients bleed spontaneously and renal failure is common in fatal cases.

As the disease progresses, severe thrombocytopenia, neutrophilia and leueopenia develop accompanied by elevated levels of aspartate aminotransferase. Within a few days of onset of symptoms, patients show signs of alteration in mental state and extreme lethargy, and usually become critically ill. In fatal cases, death generally occurs at the beginning of the second week. In non-fatal attacks the fever subsides after 10-20 days, although the patient faces a protracted period of convalescence.

Treatment of cases

No antiviral drug, vasoactive agent or cytokine has been shown to alter the course of disease. It has been possible to demonstrate an almost complete absence of normal platelet aggregation in infected monkeys, but attempts to reverse this abnormality with antioxidants and/or prostacyclins had no effect on mortality.

Recent work suggests that hyperimmune serum may modify the severity of disease, but no trials in human disease have been possible. Experiments suggest that plasmid vaccines elicit significant antibody responses, but therapeutic trials are several years away. Supportive treatment such as intravenous fluid replacement blood transfusions, nutritional support, haemodynamic support and active management of renal failure almost c improve the prognosis, compared with that of patients in rural; areas where such treatments are not available. It is important to make as much action management as possible available to patients.

Public Health Measures

Ebola fever is notifiable or reportable in most Western Countries, and the World Health Organisation should also be informed of cases and outbreaks. Ebola virus is a hazard category 4 organism, which should be handled in a containment level 4 laboratory. Hygiene measures such as the use of universal precautions in healthcare, the provision of protective overalls, disposable gloves and disposable syringes, needles and wipes are extremely important. Education about handwashing, disposal of soiled items, and the immediate disposal of bodies in secure body bags are essential in outbreak situations.

When sporadic (imported or laboratory-acquired) cases are suspected in non-endemic countries, strict isolation and barrier nursing are recommended, and the handling of biological specimens (especially for diagnosis and patient management) is carried out according to regulations governing risk assessment and control. Contacts of cases, or individuals with exposure in laboratories are placed under health surveillance for 21 days after their last exposure to infection. If they become feverish, they undergo risk assessment and may be admitted to strict isolation pending the results of diagnostic tests.