Selected Case Studies of Infectious Disease

This section examines a few example infectious diseases that have received significant attention due to their virulence and / or mortality.

	SARS - severe acute respiratory syndrome
	HIV / AIDS - acquired immunodeficiency syndrome
	West Nile - encephalitis / meningitis
	Avian Influenza
	Ebola - hemorrhagic fever
	Mad Cow - Creutzfeldt-Jacob disease
	Marburg Virus - hemorrhagic fever

The section below provides a brief synopsis for each of the example infectious diseases involved in pandemic and other high-profile outbreak events that have occurred in recent years.

SARS

SARS  stands for Severe Acute Respiratory Syndrome. SARS is a highly infectious viral respiratory illness which can often be fatal, causing concern for the well-being of patient and practitioner alike. . First reported in Asia in 2003, SARS has since been determined to be  caused by a corona virus.  SARS caused significant losses of life in multiple countries and many millions of dollars of financial losses.

A few months following the first outbreak, the illness spread to many other countries including North and South America,  Europe and Asia. The fact that outbreaks could spread to countries across the world through air travel immediately brought a sense of exceptional urgency with travel restrictions and other preventative measures. The following chart lists global SARS cases occurring in that period.

The W.H.O. (World Health Organization) reported ~ 8,000 individuals contracted SARS during the 2003 outbreaks. Of these cases, there were 774 fatalities.

Transmission of SARS

SARS infection is transmitted through close personal contact - direct contact with body fluids / secretions, exhaled viral particles, etc.  This represents contact typically within  three feet or less and may involve physical contact. The possibility of transmission decreases with distance. Sneezing, coughing (and other respiratory outputs) launch active viral particles into the immediate air and accumulate on the patients lips, skin, clothing - all in the immediate vicinity. Physical contact with objects nearby can also transfer live virus onto furniture, clothing, etc. Exactly how long and far SARS can be transferred by airborne currents is not yet known.

Symptoms

	High fever (> 38.0 ºC)
	Body discomfort, headache
	Variable mild respiratory symptoms (early on)
	Possible diarrhea (minority of cases)
	Dry cough (two days to one week)
	Pneumonia develops in most patients

In 2003 Health Canada provided the following information on diagnosis and laboratory testing for SARS: http://www.phac-aspc.gc.ca/sars-sras/pdf/SARS-CoV-lab-investigation-protocol_e.pdf

Health Canada also provided instructions for Quarantine Officers in an SARS outbreak:  http://www.phac-aspc.gc.ca/sars-sras/pdf/sars-icguidancequatineofficers-04-03_e.pdf

Treatment

Although there is no specific treatment for SARS a range of measures have been employed depending on the forms disease presentation. Accumulation of fluids in the lungs and depressed respiratory function  These include:

1. Antibiotics - usually given early while there are general respiratory infection symptoms
2. Antiviral Medications - Ribavrin - antiviral nucleoside blocks DNA / RNA replication
3. Assisted Ventilation - breathing support as required
4. Other - Tamiflu©,  protease inhibitors, interferons, immunoglobulin therapy

Current Prospects

There are no known SARS outbreaks currently. The last reported case was in 2004 in a laboratory accident in China involving mis-handling of the SARS corona virus.

With the first recorded case reported in 1981, HIV is now estimated to have infected just under 40 million people worldwide and is considered a pandemic. It is estimated that 25 million individuals have died as a result of AIDS, ranking it as the top pandemic in recorded history. 

http://www.p.chiba-u.ac.jp/lab/bukka/map.png

The Disease

HIV is a retrovirus that directly affects the immune system, harming T Cells, macrophages and the other components of the immune system. When the immunological damage becomes extensive the patient is considered to have AIDS and a very poor prognosis. Diagnosis of the progression of the infection is determined through counts of CD4+ cells of the immune system.

http://news.bbc.co.uk/nol/shared/spl/hi/africa/03/biology_of_aids/img/early_stages_320.gif

Untreated, HIV will progress to AIDS in nine to ten years. AIDS is highly lethal - survival with AIDS is approximately nine months on average. There is however, exceptional variation between individuals with AIDS, with reported survival ranging from less than a month to over two decades.

It is not the human immunodeficiency virus which directly causes the mortality, rather it is secondary infections and tumors which develop as a consequence of the patient's severely compromised immune system.

Transmission

In addition  to transmission via direct sexual contact there are other mechanisms for HIV / AIDS infection:

	Sexual contact
	Blood transfusions (rare in countries with screening programs)
	Sharing of syringes / needles with an infected individual
	Pre-birth infection from mother to fetus
	Laboratory accidental infection
	Other sources: semen, vaginal fluid, breast milk, saliva, and tears

It is important to observe that HIV has not made the jump to biting insects such as mosquitoes which could dramatically alter the incidence and distribution of the disease.

HIV /AIDS Stages

The W.H.O. (World Health Organization) has identified a series of stages representing the typical phases of HIV / AIDS. These include:

Stage 1.  No symptoms / asymptomatic, (not recognized as AIDS yet)

Stage 2.  Upper respiratory tract infections and other minor symptoms

Stage 3.  Chronic diarhea, severe bacterial infections and tuberculosis

Stage 4.  Bronchial, esophageal, tracheal disease indicating full AIDS

 

Current Prospects

Although there has been limited success with antiviral agents such as AZT, there is no known cure for AIDS.  It is reported, however, that there are cases of African prostitutes who have carried the HIV virus for years and have not developed AIDS itself. Individuals who possess a genetic variation (CCR5-Δ32) are able to resist infection from certain strains of HIV. Researchers have been intensely focused on examining their immune response and have been conducting intensive studies on their blood samples in the hopes of understanding the mechanism of their resistance. 

With respect to prevention, transmission of the HIV / AIDS virus can be blocked through the use of approved latex condoms during sex. Although no form of protection is 100 % effective there is a tremendous reduction in personal risk when condoms are employed. Other preventative measures have included needle programs have  reduced AIDS infections among intravenous drug users and educational programming on the proper use of condoms.

Avian Influenza (Bird Flu)

Avian influenza is caused by viruses found in bird secretions including feces and saliva. There are both low and high pathogenic forms and three general groups of avian flu. These include:

Influenza A H5

	High or low pathogenicity
	H5 infections can cause severe illness and death

Influenza A H7

	High or low pathogenicity
	Rare in humans - occurs when there is direct contact with infected birds
	Symptoms may upper respiratory infection and / or conjunctivitis

Influenza A H9

	Low pathogenic form (currently)
	Three H9 infections confirmed in humans

The virus can be carried by wild bird populations who do not become ill.   Domestic birds can become infected y direct contact infected wild populations or food / water which has been exposed to the virus. In birds the low pathogenic form is often undetected. The high pathogenic form however, has a lethality of 90-100 % often in less than a two day period.

Transmission

Transmission to humans is largely from infected birds or their feces or cages and usually involves the "A" influenza subtype. Horizontal transmission between humans quite rare - the majority of cases of avian influenza  in humans have been caused by contact with infected poultry (domesticated chicken, turkeys etc.).

Symptoms of avian influenza in humans have ranged from typical human influenza-like symptoms (e.g., fever, cough, sore throat, and muscle aches) to acute respiratory distress. The symptoms of avian influenza may depend on which virus caused the infection.

Avian influenza A H5N1 has caused the greatest number of human mortalities. There has been approximately 50% mortality for those infected in recent outbreaks in Europe and Asia.  Since avian viruses do not normally affect people, humans have very little immune response to this type of infection.  Should the virus mutate such that person-to-person infection becomes possible the potential pandemic would be highly significant.  Currently, there is no commercially available vaccine to protect humans against the avian H5N1 virus. The World Health Organization reports 227cases of human avian flu with 129 deaths.

One of the ways propagation of this disease is being reduced is the ban of infected bird and poultry products. This type of ban restricts import of birds or bird products (including eggs) either dead or alive.

Ebola

Ebola virus was first reported in the Congo in 1976. The causative agent of hemorrhagic fever, Ebola virus causes often-fatal infection in various primates including humans.  Ebola hemorrhagic fever is caused by a Filoviridae RNA virus belonging to one of three species: Ebola Zaire, Ebola Sudan and Ebola Reston. Mortality from Ebola hemorrhagic fever ranges from approximately 50 - 87%. 

In the fall 2007 there has been a significant outbreak on Africa: "

"For the past four weeks the number of dead in the districts of Kelle and Mbomo has continued to climb daily, as the Ministry of Health and World Health Organisation have struggled to contain what they suspected was an outbreak of Ebola. Confirmation came late last night, after blood samples from residents of Kelle were analysed in a Libreville laboratory, one of fewer than 10 in the world able to test for Ebola." (source: bbc news 2007)

Transmission

The Ebola virus is zoonotic (animal-based) and is normally found maintained in an animal hosts in a number of regions of Africa. Incidences of the EHF (Ebola Hemorrhagic Fever) have been reported in a number of African nations including:

	Congo
	Gabon
	Ivory Coast
	Sudan
	Uganda

It is suspected that individuals become infected through contact with a diseased primate / animal, either directly or through contact with infected saliva or feces. Secondary infections to those providing aid to an infected person can also occur with the virus traveling through and decimating whole families.

WHO History of Ebola Outbreaks

Year	Country	Virus subtype1	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	Côte d’Ivoire	Ebola-Côte d’Ivoire	1	0	0%
1995	Liberia	Ebola-Côte d’Ivoire	1	0	0%
1995	Democratic Republic of Congo (formerly Zaire)	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	12	1	100%
2000 - 2001	Uganda	Ebola-Sudan	425	224	53%
2001 - 2002 (Oct 2001 - March 2002)	Gabon	Ebola-Zaire	65	53	82%
2001 - 2002 (Oct 2001 - March 2002)	Republic of Congo	Ebola-Zaire	59	44	75%
2002 - 2003 (Dec 2002 - April 2003)	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%
2004	Sudan		20	5	25%
2005 (25 April to 16 June)	Republic of Congo		12	9	75%
Total			1880	1301

http://www.who.int/mediacentre/factsheets/fs103/en/index1.html

The incubation period for Ebola hemorrhagic fever can range from two days to three weeks, although the actual illness itself is both acute as well as rapid. Symptoms include fever, sore muscles and aches, headaches, vomiting, red eyes and rashes. It is not yet clear why some individuals succumb while others recovery from Ebola hemorrhagic fever, although those whose immune system is actively resisting the infection appear to fair better.

http://webs.wichita.edu/mschneegurt/biol103/lecture17/Ebola_patient.jpg

Treatments for Ebola hemorrhagic fever are based on alleviating symptoms such as maintaining respiratory function as well as electrolyte balance through administration of fluids. Since  the natural reservoir of Ebola virus is unclear it is difficult to design effective preventative measures. Research is continuing.

Mad Cow /  BSE  (bovine spongiform encephalitis)

Creutzfeldt-Jacob disease (CJD) is a severe prion-based infectious disease acquired through the ingestion of infected meat. The parallel condition in cows, bovine spongiform encephalitis (BSE), is a slow but  progressive brain disease. The first cases of BSE likely commenced in the 1970-s - 1980's.

The source of the condition was likely the result of making cattle feed from diseased sheep meat infected with scapies. In Britain, the continued use of rendered meat and bone products to feed livestock probably spread the condition considerably. By 2005 approximately 185,000 cases of BSE had been reported in British cattle.

Epidemiological studies strongly indicate that the ingestion of BSE-infected meat (cooked or raw) is the probable causative agent of Creutzfeldt-Jacob Disease in humans. The discovery that the prion believed responsible for CJD was thermally stable and able to withstand cooking temperatures while remaining highly infectious was of critical importance. Prior to this outbreak, it was believed that cooking would eliminate all pathogens from foodstuffs.

http://www.nlm.nih.gov/medlineplus/ency/images/ency/fullsize/17146.jpg

CJD in Humans

Creutzfeldt-Jakob disease is a rare but fatal brain disorder. The condition is degenerative (continually worsens) and doesn't typically present symptoms until age 60. Survival is usually less than one year. The only positive confirmation of CJD is via brain biopsy since many of the symptoms are difficult to distinguish from other forms of dementia. There is no treatment for this condition, thus most of the focus is on prevention through elimination of  the causative Bovine  Spongiform Encephalitis.

BSE Control Measures

Control of CJD is mediated through elimination of BSE-infected meats. These control measures include:

	Surveillance of bovine health
	Elimination of sick animals
	Banning of cow components subject to infection
	Ban on cows older than 30 months (no exposure to BSE in feeds)

A highly effective program in Britain has eliminated all animals older than 30 months from being used as a source of food for humans or other animals.