The review of the epidemiological evidence on Ebola Hemorrhagic Fever (EHF) from emerging viral infection perspective by Viktor Poluektoff

By | 15th May 2012

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Introduction      

“We can close the book on infectious diseases”

Surgeon-general of the U.S., 19671

“Viruses are now taking advantage of each other to cause damage to human populations”

Dr. Pierre Formenty, WHO virus researcher, 19992

 

Not all that long ago infectious diseases were assumed to disappear after successful vaccination programmes and regular supply of new antibiotics. However the situation has changed dramatically. More than 30 new infectious diseases have emerged in the past 30 years, including AIDS, a variety of viral hemorrhagic fevers and several new viral hepatitis and herpes virus infections1. Many of them are spreading from animals to humans2.

 

There is now some evidence that rapid changes in climate and ecology might be contributing to the spread of viruses viruses1. “Filoviruses are prime examples of emerging pathogens”3. International commerce, travel, uncontrolled scale of mechanized logging, limited experience in diagnosis and case management, import of nonhuman primates and bushmeat trade, the potential of filoviruses for rapid evolution and mutation – are the possible factors of their emergence3,4.

One of them, Ebola virus, was named after a river near the town of Yambuku in Zaire (now DRC), because the prototype strain was isolated during the epidemic that began in the local mission hospital on 1 September 19765. “Many aspects of the virus are unknown and have eluded medical scientists for three decades. It is highly contagious and virulent; no vaccination or cure has been found”6. In statistical terms EHF is at the bottom of Africa’s long list of infectious diseases, but high index of illness severity together with high mortality rates necessitate labelling it the “emergency”6.

Methods and Definitions

Aberdeen University Medical Library with Internet support was the primary source in literature search for this review. Some useful articles were obtained from peer-reviewed E-Journal database “sciencedirect.com” (Elsevier Science Inc.), affiliated with bibliographical database vendor “OVID”. WHO website is a very comprehensive information source itself as well as providing links to other relevant organization websites like Eurosurveillance and SPB (Centre for Disease Control and Prevention). “bbc.co.uk” was very helpful in obtaining photographs and up-to-date information. BMJ, Lancet, Scientific American e-databases and Internet search engine “Google” were considered among other sources. Finally, Dictionary of Classification of Diseases and Medical Reference Dictionary were used to give case definitions and classification codes.

EHF- is a febrile illness, marked by fever, systematic haemorrhage and high mortality; it affects humans and nonhuman primates and has appeared sporadically in epidemic form in Africa7,8. Belonging to Filoviridae family, it comprises four distinct subtypes: Zaire (identified 1976), Sudan (1976), Cote d’Ivoire (1994) and Reston (1989). The first three viruses are known to cause illness in humans. But fourth subtype, the Reston virus, identified in the U.S. and found in the Western Pacific, has only caused disease in nonhuman primates, thus it is not fully covered in this review. The natural reservoir of EHF is unknown, limiting the study of the disease, but it seems to reside in the rain forests of the African continent7,8.

In International Classification of Diseases “EHF” (A 98-4) goes with “Other viral hemorrhagic fevers, not elsewhere classified”(A98), which is a subcategory of “Arthropod-borne viral fevers and viral hemorrhagic fevers”(A90-A99) related to “Certain infectious and parasitic diseases generally recognized as communicable or transmissible”(A00-B99)9.

The definitions of some common terms used in articles regarding EHF are provided below for reference10/sup>:

Reservoir – – any person, animal, arthropod, plant, soil or substance in which an infectious agent normally lives and multiplies. The infectious agent primarily depends on the reservoir for its survival.

Nosocomial infection – an infection, occurring in a patient, which is acquired at a hospital or other healthcare facility. Commonly called – cross infection.

Enzootic – a disease, which is constantly present in the animal community, but only occurs in a small number of cases.

Biosafety level 4 – used for diagnosis of exotic agents that pose a high risk of life-threatening disease, which may be transmitted by aerosol route and for which there is no vaccine or therapy.span>

ELELISA (enzyme-linked-immunosorbent serologic assay) – a technique that relies on an enzymatic conversion reaction. It is used to detect the presence of specific substances, such as enzymes, viruses, antibodies or bacteria.

Routine data and descriptive studies

   Filoviruses are extremely pathogenic in humans and cause fatal hemorrhages, hence classified as biosafety level 4 hazardous biologic agents, posing a serious threat to health caregivers6 (in some cases over a quarter of all fatalities3). In addition to destroying the cells they infect, filoviruses might suppress the immune system. This may be one of the reasons they are so lethal: Ebola victims usually die without evidence of an effective immune response11sup>.

Although there are signs of natural immunity12, , scientists do not understand, why some people are able to recover from EHF and others not10. There were people tested positive 30 days after infection, but virus eventually died out without killing them. EHF appeared to be self-limiting in the surviving patient12sup>, who shows improvements by the second week after infection6. Furthermore, there were Ebola-infected cases without clinical symptoms at all5.

On average, incubation period lasts 1 week, depending on virus type, and patient is not contagious to others3. Clinical manifestations include influenza-like symptoms, sore throat, diarrhea and abdominal pain3, often followed by vomiting, diarrhea, rash, impaired kidney and liver function, and in some cases, both internal and external bleeding8. “EHF does not infect any cell, but it has a very specific tropism for liver cells and cells of the immune system. Massive destruction of the liver is a hallmark feature.”12

“Four types of EHF differ in pathogenicity, antigenicity and genomic composition.”5 Zaire-Ebola virus causes the greatest devastation with case fatality rates of 70-90% and Sudan subtype, with lower degree of virulence, produces mortality rate of 50-70%. All outbreaks of EHF have been genetically different from those previously isolated13,6sup>.

As epidemic continues, the mortality rates progressively decline. The main determinant of survival is age at the beginning of infection: case-fatality rate is usually lower for patients aged <15 years, and higher for those >59 years3.

Ebola outbreak chronology:

Year Country Virus subtype Cases Deaths Case fatality
1976 Sudan Ebola-Sudan 284 151 53%
1976 Zaire (DRC) Ebola-Zaire 318 280 88%
1977 Zaire (DRC) Ebola-Zaire 1 1 100%
1979 Sudan Ebola-Sudan 34 22 65%
1994 Gabon Ebola-Zaire 52 31 60%
1994 Cote d’Ivoire Ebola-Cote d’Ivoire 1 0 0%
1995 Liberia Ebola-Cote d’Ivoire 1 0 0%
1995 Zaire (DRC) Ebola-Zaire 315 250 81%
1996 (Jan-April) Gabon Ebola-Zaire 37 21 57%
1996-1997 (July-Jan) Gabon Ebola-Zaire 60 45 74%
1996 South Africa Ebola-Zaire 1 1 100%
2000-2001 Uganda Ebola-Sudan 425 224 53%
2001-2002 (Oct 01-March 02) Gabon Ebola-Zaire 65 53 82%
2001-2002 (Oct 01-March 02) Republic of Congo Ebola-Zaire 59 44 75%
2002-2003 (Dec 02-April 03) Republic of Congo Ebola-Zaire 143 128 89%
2003 (Nov-Dec) Republic of Congo Ebola-Zaire 35 29 83%
2004 Sudan Ebola-Sudan 17 7 41%
Total 1848 1287

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Analytical studies

ThThe occurrence of EHF epidemics has clustered temporarily in 1976-79, 1994-96 and 2000-02. The explanations may lie in climatic conditions13: “the anomalies of low rainfall appear to “trigger” the emergence of EHF during the vegetation recovery period, after the rains begin.”13sup> Outbreaks occurred mostly in forests during the rainy season, where dead apes were found, infected with the virus6. Non-human primates and forest antelopes, both dead and alive, have been a source of infection for humans8,13.

The remoteness of the contaminated areas made it difficult to establish reliable communication and transportation of health workers and materials for barrier nursing13. “Nosocomial transmission is responsible for amplification of the epidemic.”13 I In the hospital settings in Africa, transmission of EHF (among hospital staff too) has been associated with the reuse of unsterile needles and syringes, and inappropriate barrier precautions to prevent exposure to virus-infected body fluids (blood, secretions, etc.) or soiled clothing or bed linens of infected patients8sup>.

As human-to-human transmission (highest during late-stage disease3) requires close contact, individual behavior and local customs are central in the epidemic development5. Aerial transmission was thoroughly examined in the families of 34 cases in 1979 epidemic, which showed no risk due to simple cohabitation in the same room. Those, having intimate physical contact with patients, had a fivefold higher risk than those living under the same roof5. Burial ceremonies, when mourners touch the body of deceased person, are considered as independent risk factor for exposure due to high levels of viral antigens and particles in skin tissues3,8.

Detection and prevention

DiDiagnosis is based on clinical symptomatology, serologic tests and virus isolation, performed in biosafety level 4 facility3. Tissue samples should be sent from anybody who might have been exposed to the affected area. Blood and stool cultures should be obtained to isolate the virus3. Laboratory ELISA testing, immunoglobin ELISA and polymerase chain reaction (PCR) are used to diagnose a case of EHF within few days of the onset of  symptoms10. A practical diagnostic test that uses tiny samples from patient’s skin has been developed to diagnose EHF retrospectively in suspected case-patients who have died10sup>. New developments in diagnostic techniques include non-invasive methods (testing saliva and urine samples) and testing inactivated samples to provide rapid laboratory diagnosis to support case management during outbreak8.

Few established primary preventive measures exist because the identity and location of the natural reservoir of the Ebola virus is unknown. Early detection and simple precautionary measures may help to avoid widespread viral transmission3. Ironically, the transmission during one outbreak was curtailed after the closure of the hospital due to high mortality rates of the medical staff3.

Barrier nursing techniques include wearing protective clothing; use of infection-control measures and strict isolation of infected person3. Suspected contact tracing is essential8. . All hospital personnel, as well as communities affected by EHF, should be informed on the nature of the disease and its routes of transmission, including outbreak containment measures and strict burial techniques of the deceased3,8. Any suspected cases of EHF should be reported to local and state health authorities.

Several vaccine candidates are being tested, but it can take some years before any availableup>8,12,14.

In conjunction with WHO, CDC has developed practical, hospital-based guidelines, describing how to recognize cases of EHF and prevent nosocomial transmission by using locally available materials and few financial resources10. Available on Internet.

 

Conclusions and recommendations

EHF typically appears in sporadic outbreaks, usually spreading within a health-care setting. It is likely that isolated cases occur as well, but go unrecognized10sup>. Simple isolation precautions and change in funeral custom has contributed to limiting the outbreak5.

To avoid further epidemics, better training programme is needed for local practitioners and nurses as well as additional methods of EHF early detection10. The surveillance of the suspected areas and the knowledge of the natural reservoir of EHF and how the virus is spread can help to prevent future outbreaks significantly10sup>.

Compared to other illnesses such as Tuberculosis or Hepatitis, Ebola virus, actually, poses a rather limited threat: precisely because it kills its victims so quickly, it cannot easily spread11. But all pathogens tend to mutate, sometimes leading to appearance of more resistant versions (like drug-resistant strain of TB)11.

Encroachment into the tropical rainforests has probably been responsible for the introduction and spread of HIV and several potentially lethal viral hemorrhagic fevers1. It is just as important to recognize, that human-caused social and environmental changes are the underlying cause for the spread of “old” infectious diseases and the emergence of the new ones1,4.

 

References

1.   Snell, Noel J. C., 2003. Examining unmet needs in infectious diseases. DDT [online], volume 8 (1).

Available from: http://sciencedirect.com/science?_ob=MImg&_imagekey=B6T64/

[Accessed 29 October 2004]

 

 

2.   World: Africa fighting back at Ebola. [online] URL

http://news.bbc.co.uk/1/hi/world/africa/255353.stm

[Accessed on web 30 October 2004]

 

3.   Boardman, Amy, MD., 2003. Viral Hemorrhagic Fever. Primary Care Update for < OB/GYNS [online], volume 10 (2).

Available from: font> http://sciencedirect.com/science?_ob=MImg&_imagekey=B6TBM/

[Accessed 29 October 2004]

 

4.4.   Kuiken, et al., 2003. Emerging Viral Infections. Current opinion in Biotechnology [online], 14.Available from: http://sciencedirect.com/science?_ob=MImg&_imagekey=B6VRV/

[Accessed 30 October 2004]

 

5.   Le Guenno, B. and Galabru, J., 1997. Ebola Virus. Bulletin de l’Institut Pasteur [online], 95.Available from: font> http://sciencedirect.com/science?_ob=MImg&_imagekey=B6VKP/

[Accessed 29 October 2004]

 

6.   Bruce, J., 2002. Ebola Fever: The African Emergency. International Journal of Trauma Nursing [online], volume 8 (2).

Available from: http://sciencedirect.com/science?_ob=IssueURL&_tockey/

[Accessed 29 October 2004]

 

7.   TaTaber’s Cyclopedic Medical Dictionary, 18 Edition, Philadelphia: F.A. Davis Company, 1997

 

8.font>   WHO| Ebola hemorrhagic fever. [online] URL

http://www.who.int/mediacentre/factsheets/fs103/en/print.html

[Accessed on web 29 October 2004]

 

9.   International Statistical Classification of Diseases and Related Health Problems, 10th revision, WHO, Geneva, 1992

 

10.   EbEbola Hemorrhagic Fever Fact Sheet. [online]URL

http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/ebola/htmfont>

[Accessed on web 18 November 2004]

 

11.   Powel, Corey S., 1996. Shaking the Ebola Tree. Scientific American [online],

August 26.

Available from: http://www.sciam.com/print_version.cfm?articleID=000AB533/

[Accessed 18 November 2004]

 

 12.&n   Murphy, F.A., The Ebola virus: Virology, Fiction and Threat to Mankindi>. [online] URL

http://cygnus.sas.upenn.edu/African_Studies/Current_Events/ebola.html

[Accessed on web18 November 2004]

 

13.   Arthur R.R., Ebola in Africa – discoveries in the past decade. [online] URL

http://www.eurosurveillance.org/em/v07n03/0703-222.asp

[Accessed on web 29 October 2004]

 

14.&n   Nabel, Gary J., 2003. Vaccine for AIDS and Ebola Virus Infection. Virus Researchi> [online], 92.

Available from: http://sciencedirect.com/science?_ob=MImg&_imagekey=B6T32/

[Accessed 29 October 2004]