HISTORY 135F

Infectious and Epidemic Disease in History

Department of History
University of California, Irvine
 Instructor:    Dr. Barbara J. Becker

Lecture 19.  Hemorrhagic Fevers.

Marburg, Germany--August, 1967

Three employees at Behringwerke AG, a virus-production facility, fall sick

  • initial symptoms of fever, prostration, vomiting, and diarrhea leads to a preliminary diagnosis of dysentery, but no microbial agents are found to support that diagnosis
  • despite all efforts, the individuals worsen and die
Identical cases soon show up in Frankfurt and (later) Belgrade, Yugoslavia
  • 31 cases altogether; 23 in Marburg
  • symptoms:
    • vivid rash
    • reddening of skin on face, trunk, and extremities
    • peeling skin
    • hair and nail loss
    • severe hemorrhaging from nose, gums or sites where blood has been drawn
    • bleeding from stomach and bowels
    • vomiting of blood
    • confusion, coma, restlessness, disturbed behavior

Victims shared one common factor--contact with African green monkeys

Cercopethecus aethiops

Cells from kidneys of green monkeys:
  • grow very well in flasks
  • provide a suitable culture medium for growth and testing of viruses

Employees at Behring were harvesting monkey kidney cells for production of polio virus vaccine.

The green monkeys being used in this procedure were:

  • trapped in an area 500 miles from Nzara, Sudan
  • transported to Germany from Uganda after quarantine at London airport

Subsequent tests on guinea pigs turned up an organism that no one had ever seen before--family of viruses now called the Filoviridae ...

___________

Ebola

Nzara, Sudan (population 20,000)
June 1976

June 27--Yusia falls sick

  • lived 10 mi outside of town
  • worked as tallyman in cotton factory:
Nzara cotton factory
  • symptoms:
    • pain in the forehead
    • sore throat (like a ball of fire)
    • dry tongue
    • tiny painful ulcers on cheeks
    • muscle pains in chest, neck and small of his back
    • face became sunken and drained of expression
  • cared for by brother, Yasona
June 30--Yasona takes Yusia to local hospital
  • Yusia's symptoms:
    • cramping abdominal pain
    • diarrhea
    • vomiting
    • prostration

July 2--Yusia's symptoms worsen

  • starts to bleed profusely from nose and mouth
  • diarrhea becomes bloodstained
  • face looks like a skull mask
July 6--Yusia dies

July 13--Yasona becomes sick (eventually recovers!)

July 12--Bullen, storekeeper from cotton factory becomes ill

  • lived in-town
  • worked at table adjacent to Yusia's
Interior of the store room in Nzara cotton factory where Yusia and Bullen worked; near the ceiling, the walls are stained by bat droppings and urine leading some investigators to suspect the bats as hosts for the disease.

July 14--Bullen dies

  • one of Bullen's two wives becomes sick; dies July 19
July 18--Paul becomes sick
  • worked at the cotton factory in room next to office where Yusia and Bullen had kept tallybooks and records
  • bachelor with many social contacts
  • lived next door to merchant, Mohammed
  • played with Mohammed's assistants, Samir and Sallah, in small jazz band at local nightclub
  • comforted during illness by girlfirends
  • after his death, body was bathed by these women and his fiancée, Hawa
July 26--Samir becomes sick
  • nursed by his brother
August 16--Samir dies

August 18--Sallah becomes sick and dies; as does one of Mohammed's sons

August 21--Mohammed becomes sick

  • leaves town and travels to hospital in provincial capital, Juba
  • discharges himself and travels to Khartoum
August 30--Mohammed dies

Epidemiologists later trace 48 cases of illness and 27 deaths to contact with Paul.

Yambuku, Zaire (now Democratic Republic of the Congo [DRC])
August, 1976

(Belgian Catholic Mission Hospital in Yambuku
services 60,000 villagers in central Bumba Zone)

August 12-22

  • teacher named Mabalo Lokela toured an area near the border with the Central African Republic with small group from Yambuku mission
August 26--Mabalo falls ill
  • diagnosed with relapse of malaria
August 28--unknown man from Yandongi seeks help at Yambuku mission hospital
  • symptoms:
    • diarrhea
    • nosebleed

August 30--despite deteriorating health, man discharges himself from hospital

  • is never seen again
September 1--Mabalo's symptoms grow worse
  • medical staff at Yambuku hospital advise him to go home and rest
  • other patients at hospital show signs of illness, but symptoms (fever, fatique, diarrhea) are attributed to a variety of causes:
    • vitamin deficiency
    • post-operative recovery
    • malaria
  • these patients are also discharged and sent home
September 5--Mabalo returns to hospital in critical condition
  • symptoms:
    • profuse bleeding from all orifices
    • hospital staff at a loss
  • his wife, Mbunzu, continues to nurse him
September 8--Mabalo dies
  • Mbunzu, following tribal custom, washes her husband's body
  • Mabalo's mother, Mbunzu's mother and sister, and other women friends prepare Mabalo's body for burial
Family and friends of an early Ebola victim participate in traditional funeral preparations.
  • nearly all of these individuals later become sick
  • Mbunzu and her sister recover
  • Mabalo's mother and mother-in-law die
  • others in the surrounding area become sick
  • members of nursing staff at Yambuku hospital fall ill leading to widespread panic and disorder
  • blood is taken to test for antibodies to typhoid bacillus
September 15--Dr. Ngoi Mushola arrives from Bumba

September 17--he issues first official report of the events
 

"An Inquiry into the alarming Cases in the Collectivity
of Yandongi, 15-17 September 1976"

I received an urgent call from Yambuku on September 15 from the medical assistant Masangaya Alola Nzanzu of Yambuku Hospital because of alarming cases in the community since September 5, 1976; I went to determine the reality of the situation.

Findings.  The affliction is characterized by a high temperature around 39°C; frequent vomiting of black, digested blood, but of red blood in a few cases; diarrheal emissions initially sprinkled with blood, with only red blood near death; epistaxis [nosebleeds] now and then; retrosternal and abdominal pain and a state of stupor; prostration with heaviness in the joints; rapid evolution toward death after a period of about three days, from a state of general health....

  • identifies Mabalo as index case
  • notes panic in the surrounding villages
  • seeks assistance from Kinshasa
September 23--two professors from National University of Zaire arrive in Yambuku
  • microbiologist and epidemiologist plan six-day investigative study
    • analyze blood samples for malaria, parasites and bacteria
    • perform autopsies, preserving samples for further testing
    • return to Kinshasa after only 24 hours
    • bring three ailing patients with them

Early October--team of medical experts arrives in Yambuku

  • place hospital under strict quarantine
    • village elders in Bumba Zone advise everyone to remain at home
    • all commercial and social activity in region comes to a halt
  • receive news of similar outbreak in Sudan, raising fear of pan-African epidemic
October 11--Pasteur Institute in Paris receives package containing blood samples and a note:
 
October 10, 1976

Sir, the enclosed tubes contain blood samples collected at a mission October 4 to 9 on patients and illness contacts at the hospital of the Catholic Mission of Yambuku, Bumba Zone.... 

This village of Yambuku and another close neighbor, Yandongi, are currently seized by a deadly epidemic of indeterminant nature.  It began September 5.  It is now in regression (10-9-76).... 

The first assumptiosn were that the region was hit by yellow fever (but four of the dead Belgian missionaries were vaccinated) or typhoid fever. 

The first analysis done at the Institute of Tropical Medicine (IMT) of Anvers eliminated yellow fever and typhoid; a virus not seen before was isolated at Anvers.

We have not yet received results of a liver biopsy sent to Dara.  A diagnostic assumption of Lassa [fever] has been advanced, but not proven to date.  The fresh blood samples have been preserved on dry ice.

Dr. G. Raffier
French Embassy, Kinshasa

_______________

The infecting agent in the Yambuku epidemic was identified as a virus, another of the filoviridae.  It was named Ebola, after the Congo's Ebola River, where it was believed to have originated.

Comparison of the viruses responsible for the disease outbreaks in Sudan and Zaire revealed them to be distinct strains of ebola virus.  Of the two, ebola Zaire was the more virulent.

In 1989, third strain was discovered during an outbreak among monkeys in a research laboratory in Reston, Virginia.  No humans became sick from their exposure to this strain although some did develop antibodies to it.

In 1995, a fourth strain was found.  Chimpanzees in the Tai Forest, Ivory Coast, died of this strain.  One researcher studying this outbreak became ill, but recovered.

Chronology of Ebola Outbreaks
When
Where
Cases (Deaths)
June 1976 Nzara, Sudan
284 (151)
August 1976 Yambuku, Zaire (now Democratic Republic of the Congo [DRC])
318 (280)
1979 Nzara, Sudan
34 (22)
1989 and 1990 Reston, Virginia
(also found in other animal research facilities in Texas and Pennsylvania)
0 (0)*
*all cases of illness were confined to monkeys imported from one facility in the Philippines; although no human was sickened by the virus, some who had contact with these monkeys were later found to have developed antibodies to the virus
1992 Siena, Italy *see comments above
1994 Minkebe, Gabon
52 (31)
1995 Kikwit, DRC
315 (255)
1996 Mayibout, Gabon
Boue, Gabon
37 (21)
60 (45)
          Alice, Texas
Philippines
0 (0)*

*see comments above

2000-2001 Gulu, Uganda
425 (224)

Patients receive care at Lacor Hospital in Gulu.

Corpses of ebola victims are handled with great care...

...to prevent the virus from spreading.

Bodies are placed in graves by staff wearing protective clothing.

2001-2002 Mbisyangandu, DRC
59 (44)
  Mekambo, Gabon
65 (53)
2003 Mbomo, Rep. of Congo
35 (29)
2004 Yambio, Sudan
17 (7)
2005 Mbomo, Rep. of Congo
12 (9) as of 25 May 2005

 
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