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LEVEL 4
Filoviruses
(Filum-Thread)
• Despite of frequent outbreaks with high
fatality, the reservoir of EBOLA virus & its
natural history remain unclear.
"Filoviridae“
• A- MARBURG
• B- EBOLA
1.Sudan
2. Zaire
3. Reston
4. Ivory Coast ebola virus
5. Bundibugyo ebola virus
Eugene M. Johnson – ( Best field Virologist)
• They are related to
Varicella,Influenza,Mumps,
Rabies & syncytial viruses.
• What HIV does in 10 years,
EBOLA does in 10 days
• Pray to GOD that combination of
E.Zaire & E. Reston should never
take place.
KINSHASA HIGHWAY
• It connects
Kinshasa
( Place in Zaire ) to
Sudan.
• In-between there is
a cave called
KITUM CAVE.
• Near the cave there
is a mountain called
as MOUNT
ELGON.
KITUM CAVE
• KITUM CAVE ( situated in Rain Forest )-
LASA , VEE , Rift valley ( Kenya ) fever.
Rokio , Monkey pox , Guanarito virus ,
Dengue , Chikungunya , HIV , Ebola ,
Semiliki forest agent , Crimean Congo ,
Sindbis , Ononglong , Mokola , Machupo ,
Durenheg, Lentek
• And many more will come definitely – Dr.
John Johnson & Dr. Eugene M. Johnson.
Ebola river (Headstream of Mongola,Tributory of Congo )
LEVEL-4 ( Mortality Rate )
• Marburg – 25 to 30 %
• E.Sudan - 50 to 60 %
• E.Zaire - 90 % & above
• E. Reston- no mortality in human beings
• E. Ivory Coast – (Tai Ebolavirus ) on 1 November
1994 , more dead chimpanzees were discovered . Many
testings were positive to Ebola. No human deaths.
• Bundibugyo ebolavirus - On November 24, 2007, in
Uganda an outbreak of Ebola was confirmed in Bundibugyo district.
CDC & WHO confirmed the presence of the new species. 149 were
affected .37 died. (24.83 %)
FAMILY FILOVIRIDAE
• These viruses appear to be among the least successful
of negative strand RNA viruses in that they have a
restricted host range and limited distribution. They are
among the most feared by humans because of their
spectacular symptomatology and often fatal outcome of
infection
• - 80 x 800-1000nm or filaments sometimes longer
• - very long branched, 6-shaped or U shaped particles
• - helical nucleocapsids
• - genome is single negative sense ssRNA, 19Kb
• -only 2 antigenically unrelated member viruses - Marburg
virus & Ebola virus, several strains of the latter
Cont…
• Have surface spikes ( 7 nm )
• Enveloped viruses
• Virion is tubular in appearance.
• Virion contains 7 known structural protiens.
• Marburg & Ebola – almost same structure, but
antigenecity differs, thus outcome differs.
• In both types clinical presentation is same. Electron
microscopy & serological tests can differentiate them
• Crashed & bled out (Army term ) is terminal event in
both.
• They spare only bones & tendons.
• NOT ONLY ATTACK COLLAGEN TISSUE BUT
DESTROY IT.
Cont….
• The Ebola genome codes for 4 virion structural proteins
(VP30, VP35, nucleoprotein, and a polymerase protein )
and 3 membrane-associated proteins (VP40,
glycoprotein [GP], and VP24). The GP gene is
positioned fourth from the 3' end of the 7 linearly
arranged genes.
• Lethal dose of E.Zaire is 500 virions
Clinical picture
• Illness is characterized by the rapid onset of fever,
malaise, muscle pain, headache, and the inflammation of
the pharynx.
• Six days following vomiting and bloody diarrhea,
individuals may develop maculopapular rash with
bleeding at needle sites and bodily orifices.
• Bleeding (Platelet dysfunction – abnormalities of
coagulation, DIC formation )- internal bleeding to start
with, then from every orifice of body, even from EYES.
• Necrosis of liver , spleen , lungs & lymph nodes.- giving
their own symptoms.
• Attack on collagen & cartilage.
• Pharyngitis, cough, dyspnoea, abd.pain.
• Multi organ failure
Cont….
• Patients look like zombie.
• Irritability,amnesia,control
of higher centers is lost
• Haematamasis along with
pieces of intestines
• Filoviruses have very
special affinity for Testes
(orchitis) & ovaries
(ovaritis )
• Death in 7 to 15 days.
Marburg
• 1967 - Lab. Workers in Marburg (Frankfurt, Germany) &
Belgrade (Yugoslavia) – handling green (Vervet ) monkeys
(Imported from Uganda )- 31 were caught with unknown
haemorrhagic fever.
• Behring institutes- vaccine production – monkey renal
cells- Clous F. is the 1st
known victim of Marburg.
• Now accepted – 1963 – many died near mount Elgon –
this was the 1st
outbreak of Marburg.
• 1980- Charles Monet – visited Kitum cave & captured the
condition. During treatment he vomited on the face & eyes
of Dr. Shem Musoke. Subsequently he became Marburg
patient. Monet died & Musoke survived. ( Dr. David
Silverstien )
• Dr. Musoke- his blood has been preserved. Serology test
developed contains his antibodies.
• It is Musoke strain of Marburg
• In 1975, three people in Johannesburg, South Africa were
infected by the Marburg virus by a man returning from
Zimbabwe, resulting in one death. Two similar cases in 1980
and 1987 occurred in Kenya after European visitors went to
Kitum Cave. Both later died. The next major outbreak occurred
in the Democratic Republic of Congo from 1998 to 2000,
where 128 of 154 cases were fatal. This outbreak originated
with miners in Durba and Watsa in Orientale, Congo.
• Angola - On March 22, 2005, as the death toll neared 100, the
cause of the illness was identified as the Marburg virus. By
July 2005, Angola's health department reported more than 300
cases.
• On July 10, 2008, a Dutch woman, who had visited the
Python Cave during her holiday in Uganda, had been infected
with the Marburg virus. The woman died when under
treatment on 11 July. The Ugandan Ministry of Health closed
the cave after this case.
• Transmission- The disease is spread through bodily
fluids, including blood, excrement, saliva, and vomit.
• Needles – was commonest cause in African Hospitals.
• Rarely it is S.T.D.
• Diagnosis-
• Serology using Musoke antibodies.
- Marburg- Musoke
- E. Sudan – Boniface 76
- E. Zaire – Mayinga
• Microscopy
• G.pig innoculation- orchitis & ovaritis & large eosinophilic
cytoplasmic inclusion bodies.(Ebola)
• ELISA or RIA.
Ebola
• Frederick A Murphy
• EBOLA SUDAN – (July 1976 )
• Virus hosts
• › Homo sapiens (Human), Epomops franqueti
(Franquet's epauleted bat), Myonycteris torquata (Little
collared fruit bat)
• second species of Ebola emerging simultaneous with
the Zaire virus. Believed to have originated amongst
cotton factory workers in Nzara, Sudan, workers
exposed to a potential natural reservoir. Scientists tested
all animals and insects in response to this; however,
none tested positive for the virus. The carrier is still
unknown. The most recent outbreak occurred in May
2004. . The average fatality rates for were 54% in 1976,
68% in 1979, and 53% in 2000 and 2001
Cont….
• The 1st
cotton meal worker died was Mr. U.G.
• From Boniface the antibodies are obtained. Thus
this type is also called as Ebola Boniface 76.
Ebola Zaire
Sept.1976- 55 villages
around Zaire started
epidemic of unknown.
Before reaching of
rescue team, nothing
was left behind.
Most efficient & cruel
agent ( like Shark )
had its ugly game-
WHO pathology
report.
• The Zaire Ebola Virus, has the highest case-
fatality rate, up to 90% in some epidemics, with
an average case fatality rate of approximately
83% over 27 years. There have been more
outbreaks of Zaire ebola virus than any other
species. The first outbreak took place on 26
August 1976 in Yambuku. Mabalo Lokela, a 44-
year-old schoolteacher, became the first
recorded case. The symptoms resembled
malaria, and subsequent patients received
quinine. The initial transmission was believed to
be due to reuse of the needle for Lokela's
injection without sterilization. Subsequent
transmission was also due to lack of barrier
nursing and the traditional burial preparation
method, which involves washing
and gastrointestinal tract cleansin
Medical Care
• Presently, no specific therapy is available that has demonstrated
efficacy in the treatment of Ebola hemorrhagic fever.
– Ribavirin, an antiviral drug previously used in other types of viral
hemorrhagic fever, has no demonstrable anti-Ebola activity in
vitro and has failed to protect Ebola-infected primates.
– During the 1995 outbreak in Kikwit, DRC, human convalescent
plasma was used to treat 8 patients with proven Ebola disease.
Only 1 of these patients died.
– Human recombinant interferon alpha-2b used in conjunction with
hyperimmune equine IgG delayed but did not prevent death in
Ebola-infected cynomolgus macaques.
– Four laboratory workers in Russia who had possible Ebola
exposure were treated with a combination of a goat-derived anti-
Ebola immunoglobulin plus recombinant human alpha-2
interferon. One of these patients had a high-risk exposure and
developed clinical evidence of Ebola infection. All 4 patients
recovered. Equine IgG containing high-titer neutralizing
antibodies to Ebola protected guinea pigs and baboons but was
not effective in protecting infected rhesus monkeys.
• Supportive therapy with attention to intravascular volume,
electrolytes, nutrition, and comfort care is of benefit to the
patient.
– Such care must be administered with strict attention to barrier isolation.
– All body fluids (blood, saliva, urine, stool) contain infectious virions and
should be handled with great care.
– Patients who have died of Ebola should be buried promptly and with as
little contact as possible.
• Experimental therapies are being investigated.
– DNA vaccines expressing either envelope GP or nucleocapsid protein
(NP) genes of Ebola virus have been demonstrated to induce protection
in adult mice exposed to Ebola virus. These vaccines were administered
by coating gold beads with DNA expressing the genes for either GP or
NP, and they were delivered by skin particle bombardment using a
PowderJect-XR gene gun. Both vaccines induced measurable antibody
responses detected by ELISA and induced cytotoxic T-cell immunity.
– Another approach has been to raise neutralizing antibodies in goats or
horses that are specific for the GP of Ebola. These may be useful in both
vaccine design and prophylactic use.
Complications
• Ocular complications have been reported in 3 of 20 survivors (15%)
of the 1995 Ebola outbreak in the DRC. Patients reported ocular
pain, photophobia, increased lacrimation, and decreased visual
acuity. All had documented uveitis, and all improved with topical
application of 1% atropine and steroids.
• Survivors have developed the following late
manifestations:
– Myalgias
– Asymmetric and migratory arthralgias
– Headache
– Fatigue
– Bulimia
– Amenorrhea
– Hearing loss
– Tinnitus
– Unilateral orchitis
– Suppurative parotitis
Ebola Reston
• Peter B. Jahrling
• Discovered during an outbreak of Simian
hemorrhagic fever virus (SHFV) in crab-eating
macaques from Hazleton Laboratories (now
Covance) in 1989. Since the initial outbreak
in Reston, Virginia, it has emerged in the
Philippines, Siena Italy, Texas, and among pigs
in the Philippines. Despite its status as a Level-
4 organism, it is non-pathogenic to humans
however hazardous in monkeys ( 100 % deaths)
• Reston house is a monkey house in Virginia
near Washington.470 monkeys were brought
from Philippines. (From Africa). Suddenly they
started dying. Four animal handlers got infected.
None died. All recovered in 15 days.
• It is mutant of Zaire ( fortunately sleeping one )
• Among all Filoviruses , Reston is only one which
shows spread by droplet .( Respiratory Entry )
• Humans as a rule are always spared.(0 % mort.)
• Peter Jahrling & Tom Gijbert have named this
type as Reston.( found in Reston monkey house
& is taking rest )
• John Johnson – Cleaned the monkey house by
killing all monkeys.

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Filoviridae

  • 2. • Despite of frequent outbreaks with high fatality, the reservoir of EBOLA virus & its natural history remain unclear.
  • 3. "Filoviridae“ • A- MARBURG • B- EBOLA 1.Sudan 2. Zaire 3. Reston 4. Ivory Coast ebola virus 5. Bundibugyo ebola virus
  • 4. Eugene M. Johnson – ( Best field Virologist) • They are related to Varicella,Influenza,Mumps, Rabies & syncytial viruses. • What HIV does in 10 years, EBOLA does in 10 days • Pray to GOD that combination of E.Zaire & E. Reston should never take place.
  • 5. KINSHASA HIGHWAY • It connects Kinshasa ( Place in Zaire ) to Sudan. • In-between there is a cave called KITUM CAVE. • Near the cave there is a mountain called as MOUNT ELGON.
  • 7.
  • 8. • KITUM CAVE ( situated in Rain Forest )- LASA , VEE , Rift valley ( Kenya ) fever. Rokio , Monkey pox , Guanarito virus , Dengue , Chikungunya , HIV , Ebola , Semiliki forest agent , Crimean Congo , Sindbis , Ononglong , Mokola , Machupo , Durenheg, Lentek • And many more will come definitely – Dr. John Johnson & Dr. Eugene M. Johnson.
  • 9. Ebola river (Headstream of Mongola,Tributory of Congo )
  • 10. LEVEL-4 ( Mortality Rate ) • Marburg – 25 to 30 % • E.Sudan - 50 to 60 % • E.Zaire - 90 % & above • E. Reston- no mortality in human beings • E. Ivory Coast – (Tai Ebolavirus ) on 1 November 1994 , more dead chimpanzees were discovered . Many testings were positive to Ebola. No human deaths. • Bundibugyo ebolavirus - On November 24, 2007, in Uganda an outbreak of Ebola was confirmed in Bundibugyo district. CDC & WHO confirmed the presence of the new species. 149 were affected .37 died. (24.83 %)
  • 11. FAMILY FILOVIRIDAE • These viruses appear to be among the least successful of negative strand RNA viruses in that they have a restricted host range and limited distribution. They are among the most feared by humans because of their spectacular symptomatology and often fatal outcome of infection • - 80 x 800-1000nm or filaments sometimes longer • - very long branched, 6-shaped or U shaped particles • - helical nucleocapsids • - genome is single negative sense ssRNA, 19Kb • -only 2 antigenically unrelated member viruses - Marburg virus & Ebola virus, several strains of the latter
  • 12. Cont… • Have surface spikes ( 7 nm ) • Enveloped viruses • Virion is tubular in appearance. • Virion contains 7 known structural protiens. • Marburg & Ebola – almost same structure, but antigenecity differs, thus outcome differs. • In both types clinical presentation is same. Electron microscopy & serological tests can differentiate them • Crashed & bled out (Army term ) is terminal event in both. • They spare only bones & tendons. • NOT ONLY ATTACK COLLAGEN TISSUE BUT DESTROY IT.
  • 13. Cont…. • The Ebola genome codes for 4 virion structural proteins (VP30, VP35, nucleoprotein, and a polymerase protein ) and 3 membrane-associated proteins (VP40, glycoprotein [GP], and VP24). The GP gene is positioned fourth from the 3' end of the 7 linearly arranged genes. • Lethal dose of E.Zaire is 500 virions
  • 14. Clinical picture • Illness is characterized by the rapid onset of fever, malaise, muscle pain, headache, and the inflammation of the pharynx. • Six days following vomiting and bloody diarrhea, individuals may develop maculopapular rash with bleeding at needle sites and bodily orifices. • Bleeding (Platelet dysfunction – abnormalities of coagulation, DIC formation )- internal bleeding to start with, then from every orifice of body, even from EYES. • Necrosis of liver , spleen , lungs & lymph nodes.- giving their own symptoms. • Attack on collagen & cartilage. • Pharyngitis, cough, dyspnoea, abd.pain. • Multi organ failure
  • 15. Cont…. • Patients look like zombie. • Irritability,amnesia,control of higher centers is lost • Haematamasis along with pieces of intestines • Filoviruses have very special affinity for Testes (orchitis) & ovaries (ovaritis ) • Death in 7 to 15 days.
  • 17.
  • 18. • 1967 - Lab. Workers in Marburg (Frankfurt, Germany) & Belgrade (Yugoslavia) – handling green (Vervet ) monkeys (Imported from Uganda )- 31 were caught with unknown haemorrhagic fever. • Behring institutes- vaccine production – monkey renal cells- Clous F. is the 1st known victim of Marburg. • Now accepted – 1963 – many died near mount Elgon – this was the 1st outbreak of Marburg. • 1980- Charles Monet – visited Kitum cave & captured the condition. During treatment he vomited on the face & eyes of Dr. Shem Musoke. Subsequently he became Marburg patient. Monet died & Musoke survived. ( Dr. David Silverstien ) • Dr. Musoke- his blood has been preserved. Serology test developed contains his antibodies. • It is Musoke strain of Marburg
  • 19. • In 1975, three people in Johannesburg, South Africa were infected by the Marburg virus by a man returning from Zimbabwe, resulting in one death. Two similar cases in 1980 and 1987 occurred in Kenya after European visitors went to Kitum Cave. Both later died. The next major outbreak occurred in the Democratic Republic of Congo from 1998 to 2000, where 128 of 154 cases were fatal. This outbreak originated with miners in Durba and Watsa in Orientale, Congo. • Angola - On March 22, 2005, as the death toll neared 100, the cause of the illness was identified as the Marburg virus. By July 2005, Angola's health department reported more than 300 cases. • On July 10, 2008, a Dutch woman, who had visited the Python Cave during her holiday in Uganda, had been infected with the Marburg virus. The woman died when under treatment on 11 July. The Ugandan Ministry of Health closed the cave after this case.
  • 20. • Transmission- The disease is spread through bodily fluids, including blood, excrement, saliva, and vomit. • Needles – was commonest cause in African Hospitals. • Rarely it is S.T.D. • Diagnosis- • Serology using Musoke antibodies. - Marburg- Musoke - E. Sudan – Boniface 76 - E. Zaire – Mayinga • Microscopy • G.pig innoculation- orchitis & ovaritis & large eosinophilic cytoplasmic inclusion bodies.(Ebola) • ELISA or RIA.
  • 22.
  • 23. • EBOLA SUDAN – (July 1976 ) • Virus hosts • › Homo sapiens (Human), Epomops franqueti (Franquet's epauleted bat), Myonycteris torquata (Little collared fruit bat) • second species of Ebola emerging simultaneous with the Zaire virus. Believed to have originated amongst cotton factory workers in Nzara, Sudan, workers exposed to a potential natural reservoir. Scientists tested all animals and insects in response to this; however, none tested positive for the virus. The carrier is still unknown. The most recent outbreak occurred in May 2004. . The average fatality rates for were 54% in 1976, 68% in 1979, and 53% in 2000 and 2001
  • 24. Cont…. • The 1st cotton meal worker died was Mr. U.G. • From Boniface the antibodies are obtained. Thus this type is also called as Ebola Boniface 76.
  • 25. Ebola Zaire Sept.1976- 55 villages around Zaire started epidemic of unknown. Before reaching of rescue team, nothing was left behind. Most efficient & cruel agent ( like Shark ) had its ugly game- WHO pathology report.
  • 26. • The Zaire Ebola Virus, has the highest case- fatality rate, up to 90% in some epidemics, with an average case fatality rate of approximately 83% over 27 years. There have been more outbreaks of Zaire ebola virus than any other species. The first outbreak took place on 26 August 1976 in Yambuku. Mabalo Lokela, a 44- year-old schoolteacher, became the first recorded case. The symptoms resembled malaria, and subsequent patients received quinine. The initial transmission was believed to be due to reuse of the needle for Lokela's injection without sterilization. Subsequent transmission was also due to lack of barrier nursing and the traditional burial preparation method, which involves washing and gastrointestinal tract cleansin
  • 27. Medical Care • Presently, no specific therapy is available that has demonstrated efficacy in the treatment of Ebola hemorrhagic fever. – Ribavirin, an antiviral drug previously used in other types of viral hemorrhagic fever, has no demonstrable anti-Ebola activity in vitro and has failed to protect Ebola-infected primates. – During the 1995 outbreak in Kikwit, DRC, human convalescent plasma was used to treat 8 patients with proven Ebola disease. Only 1 of these patients died. – Human recombinant interferon alpha-2b used in conjunction with hyperimmune equine IgG delayed but did not prevent death in Ebola-infected cynomolgus macaques. – Four laboratory workers in Russia who had possible Ebola exposure were treated with a combination of a goat-derived anti- Ebola immunoglobulin plus recombinant human alpha-2 interferon. One of these patients had a high-risk exposure and developed clinical evidence of Ebola infection. All 4 patients recovered. Equine IgG containing high-titer neutralizing antibodies to Ebola protected guinea pigs and baboons but was not effective in protecting infected rhesus monkeys.
  • 28. • Supportive therapy with attention to intravascular volume, electrolytes, nutrition, and comfort care is of benefit to the patient. – Such care must be administered with strict attention to barrier isolation. – All body fluids (blood, saliva, urine, stool) contain infectious virions and should be handled with great care. – Patients who have died of Ebola should be buried promptly and with as little contact as possible. • Experimental therapies are being investigated. – DNA vaccines expressing either envelope GP or nucleocapsid protein (NP) genes of Ebola virus have been demonstrated to induce protection in adult mice exposed to Ebola virus. These vaccines were administered by coating gold beads with DNA expressing the genes for either GP or NP, and they were delivered by skin particle bombardment using a PowderJect-XR gene gun. Both vaccines induced measurable antibody responses detected by ELISA and induced cytotoxic T-cell immunity. – Another approach has been to raise neutralizing antibodies in goats or horses that are specific for the GP of Ebola. These may be useful in both vaccine design and prophylactic use.
  • 29. Complications • Ocular complications have been reported in 3 of 20 survivors (15%) of the 1995 Ebola outbreak in the DRC. Patients reported ocular pain, photophobia, increased lacrimation, and decreased visual acuity. All had documented uveitis, and all improved with topical application of 1% atropine and steroids. • Survivors have developed the following late manifestations: – Myalgias – Asymmetric and migratory arthralgias – Headache – Fatigue – Bulimia – Amenorrhea – Hearing loss – Tinnitus – Unilateral orchitis – Suppurative parotitis
  • 30. Ebola Reston • Peter B. Jahrling
  • 31. • Discovered during an outbreak of Simian hemorrhagic fever virus (SHFV) in crab-eating macaques from Hazleton Laboratories (now Covance) in 1989. Since the initial outbreak in Reston, Virginia, it has emerged in the Philippines, Siena Italy, Texas, and among pigs in the Philippines. Despite its status as a Level- 4 organism, it is non-pathogenic to humans however hazardous in monkeys ( 100 % deaths) • Reston house is a monkey house in Virginia near Washington.470 monkeys were brought from Philippines. (From Africa). Suddenly they started dying. Four animal handlers got infected. None died. All recovered in 15 days.
  • 32. • It is mutant of Zaire ( fortunately sleeping one ) • Among all Filoviruses , Reston is only one which shows spread by droplet .( Respiratory Entry ) • Humans as a rule are always spared.(0 % mort.) • Peter Jahrling & Tom Gijbert have named this type as Reston.( found in Reston monkey house & is taking rest ) • John Johnson – Cleaned the monkey house by killing all monkeys.