viral haemorrhagic fevers in nigeria
DESCRIPTION
viral haemorrhagic fevers in NigeriaTRANSCRIPT
VIRAL HAEMORRHAGIC
FEVERS IN NIGERIA
Dr. T. O. OrichaDept. Of Medicine
Federal Teaching Hosptal, Gombe
Outline
• Introduction
• Epidemiology
• Pathogenesis
• Clinical features
• Differential diagnosis
• Diagnosis
• Management and Treatment
• Prevention
• Ebola virus disease
• Conclusion
• References
Introduction
• Viral haemorrhagic fever (VHF) is a term first
coined by Russian physicians in the 1940s
• Syndrome of:
Fever
Constellation of initially nonspecific signs and
symptoms
Propensity for bleeding and shock
• Caused by more than 30 RNA viruses
Introduction
• Pathogenic hallmarks:
Microvascular instability with capillary leak
Impaired haemostasis
• High case fatality rates
• Correct diagnosis depends on demonstration of the infecting virus or one of its products in acute serum samples
• Barrier nursing
• Avoidance of parenteral exposure
Introduction
• 4 taxonomic families:
Filoviridae: Marburg, Ebola
Arenaviridae: Junin, Machupo, Guanarito, Sabia, Chapare, Lassa, Lujo
Bunyaviridae: Rift Valley fever, Crimean-Congo, Hantaan, Seoul, Puumala and others, Sin Nombre, Black Creek Canal, Bayou, Andes and others
Flaviviridae: Yellow fever, Dengue, KyasanurForest disease, Omsk HF, Alkhurma
Introduction
• VHFs in Nigeria:
Yellow fever (YF)
Lassa fever (LF)
Dengue HF (DHF)
Ebola HF (EHF) / Ebola virus disease (EVD)
Marburg HF (MHF)
Crimean-Congo HF (CCHF)
Rift valley fever (RVF)
Introduction
• Common characteristics of HF viruses.
Enveloped viruses with a ssRNA genome
Cytoplasmic replication
Pantropic targeting prim dendritic and
monocyte/macrophage cells
Sporadic outbreaks
Both genders and all age groups affected
Introduction
Generally asymptomatic or flu-like symptoms
Severe cases associated with high levels of
virus in blood
Rodents/insects are natural reservoirs/vectors
Continuously emerging or re-emerging
Geographically restricted by presence of
natural host
Epidemiology
Epidemiology• Map showing cases/distribution of YF
Epidemiology
Epidemiology• LF: map of Nigeria 2012 and 2013 outbreaks
Epidemiology• Reported outbreaks of LF, 16th March, 2012
Epidemiology
• Geographic distribution of EHF outbreaks and
fruit bats of Pteropodidae family
Epidemiology
• Geographic distribution of MHF outbreaks and
fruit bats of Pteropodidae family
Epidemiology
Epidemiology
• Geographic distribution of CCHF
Epidemiology• Geographic distribution of RVF outbreaks
Epidemiology
• Tomori et al; 1988
• Serosurvey for abs to viral agents with hemorrhagic febrile infections
• 1,677 human sera from different parts of Nigeria
• 357 (21.3%) +ve for Lassa
• 42 (2.5%) +ve for Rift valley
• 30 (1.8%) +ve for Ebola
• 29(1.7%) +ve for Marburg
• Abs to Lassa and RVF viruses were found in all locations in Nigeria
• EV and MV abs found mainly in northern savanna zones
Epidemiology
• Olaleye et al; 1996
• 3,121 human sera from 6 ecological zones tested for presence of abs to RVF virus, 1985-1989
• 461 sera (14.8%) showed haemagglutination-inhibiting ab
• 390 of 461 reactive sera (84.6%) revealed neutralizing ab
• Of 461 sera tested for IgM, 107 gave +ve results (23.2%)
• Higher exposure among livestock workers/wild-life rangers
• Longitudinal study of 164 febrile pxs: infection rate 6.7%.
Epidemiology
• 25 countries at risk of YF in Africa
• Nigeria among 18 affected
• West Africa worst hit; 13 of 14 countries
• Increased cases in West Africa linked to high non-immunized subjects.
• Bt 1984-1994, multifocal epidemics in Nigeria, 23,958 cases and 6,350 deaths.
• Cases reported 2000-2004 was 42
• As of 8 Feb. 2013, 38 suspected cases in 10 states
Epidemiology• cases of YF reported in Nigeria, 1950-2004
Epidemiology
• Carey et al; Aug 1964 to Dec 1968
• 32 strains of dengue virus were recovered from
febrile patients seen at UCH, Ibadan.
• 18 strains identified as dengue type 1
• 14 as dengue type 2.
• 1 April 2014, FMOH reported case of death
from DHF: 15-year old lady at Irrua Teaching
Hospital, Edo state.
Epidemiology
• Idris A. N. et al; 2013
• Sero-prevalence of DENV-3 among 256
patients with febrile illnesses in UMTH
• 26 (10.1%) had neutralizing antibodies to
DENV-3
• Titres bt 1:10 and 1:320
Epidemiology
Umoh et al; 1983
• Sera from 1164 cattles in north; 25.7% had
pptg abs against CHF-C virus
David-West TS et al; 1974
• A survey for neutralizing abs to Congo virus.
• Total sample population of 250: 141 males and
109 females
• 9 males and 15 females had +ve ab levels
Epidemiology
• These viruses are zoonotic, maintained in
nature in mammals
• Exception of dengue virus, as humans are
considered to be reservoir
• Endemic area restricted by the distribution of
natural reservoir and/or arthropod vector
• Reservoir/vector to human
• Human to human
Epidemiology
• Transmission to Humans
Inoculation into mucus membranes or broken skin of body fluids/feces
Mosquitoes or ticks
Aerosol transmission
Sexual transmission
• Large outbreaks almost always result of amplification in healthcare settings
• Risk of transmission during incubation period or from asymptomatic persons is negligible
Epidemiology• Overview of the ecology and epidemiology of
these viruses
Disease Reservoir/Vector Distribution Clinical
cases/year
YF Monkey/mosquito (Aedes
aegypti, other Aedes spp.)
Sub-Saharan
Africa, South
America
5,000-200,000
LF Rodent (multimammate rat
or Mastomys Natalensis)
West Africa 30,000-50,000
EHF Fruit bat (Egyptian fruit bat
or Rousettus aegyptiacus);
non-human primates
West, Central, East
Africa
5-500
MHF Fruit bat (Egyptian fruit bat
or Rousettus
Aegyptiacus); non-human
primates
West, Central, East
Africa
5-300
Epidemiology• Overview of the ecology and epidemiology of
these viruses
Disease Reservoir/Vector Distribution Clinical
cases/year
DHF Human/mosquito (Aedes
aegypti and albopictus)
Tropics and
subtropics
100,000-
200,000
CCHF Wild and domestic
vertebrates /tick (primarily
Hyalomma
Species)
Africa, Balkans,
South Russia,
Middle East, West
China etc
~500
RVF Domestic livestock/
mosquitoes (Aedes and
Others)
Sub-Saharan
Africa,
Madagascar, Saudi
Arabia, Yemen
100-100 000
Epidemiology• Overview of the ecology and epidemiology of
these viruses
Disease Disease-to-
infection
Ratio
Case
fatality
Human-to-
Human
Transmissibility
Risk factors for
transmission
YF 1 : 2–20 20-50% No Not vaccinated.
Sporadic cases in
jungle, outbreaks in
semi-humid
savannah
LF 1 : 5–10 10-25% Moderate Contact with rodents
and their excreta
EHF 1 : 1 25-90% High Contact with caves
or diseased primates
MHF 1 : 1 25-90% High Contact with caves
or diseased monkeys
Epidemiology• Overview of the ecology and epidemiology of
these viruses
Disease Disease-to-
infection
Ratio
Case
fatality
Human-to-
Human
Transmissibility
Risk factors for
transmission
DHF 1 : 10–100 Untreated:
10-15%
Treated:<
1
None Crowded
population; bad
water, sewage waste
systems
CCHF 1 : 1–2 15-30% High Contact with blood
of diseased animals
(ruminants)
RVF 1 : 100 10–50% None Epizootics of
ruminants. Contact
with animal blood
Pathogenesis• Viral properties
Virus Virus family Physical
Type of
Nucleic
Acid
Virus
Particle
Size
(nm)
Size of
Nucleic
Acid
in Virion
(kb/kbp)
Gene products
YF Flaviviridae ss +ve
sense
RNA
40-60
spheroidal
10.9 3 structural proteins:
capsid, premembrane, and
envelope
7 non-structural
proteins: NS1, NS2A,
NS2B, NS3, NS4A,
NS4B, NS5
LF Arenaviridae ss bi-
segment
ed
ambisen
se RNA
110-130
round,
oval, or
pleomorp
hic
10-19 Large segment: Zn-
binding protein, RNA
polymerase
Small segment:
nucleoprotein, surface GP
precursor
Pathogenesis• Viral properties
E Filoviridae ss –ve
sense
RNA
800-1100
Cylindrical
or
tubular
18-19 Nucleoprotein,
polymerase
Cofactor, matrix protein,
sGP, Δ-peptide, GP1,2,
transcription activator,
secondary matrix protein,
RNA-dependent
RNA polymerase
M Filoviridae ss –ve
sense
RNA
800-1100
Cylindrical
or
tubular
18-19 Nucleoprotein,
polymerase
Cofactor, matrix protein,
GP1,2, transcription
activator, secondary
matrix protein, RNA-
dependent
RNA polymerase
Pathogenesis• Viral properties
D Flaviviridae ss +ve
sense
RNA
40-65
spherical
11 3 structural proteins
7 non-structural proteins
CCHF Bunyaviridae ss –ve
sense,
ambisens
e triple
segment
d RNA
80–120
spherical
or
pleomor
phic
L(11-
14.4)
M(4.4–
6.3)
S(1.7–2.1)
L segment: RNA
polymerase
M segment: envelope
proteins (Gc, Gn)
S segment: nucleocapsid
protein
RVF Bunyaviridae ss –ve
sense,
ambisens
e triple
segment
d RNA
90-110
spherical
or
pleomor
phic
L(6.6)
M(3.9)
S(1.7)
L segment: RNA
polymerase
M segment: 2 SPs (Gc,
Gn), 2 NSPs (78 kDa
and 14 kDa NSm
protein)
S segment: structural
nucleoprotein, small
NSP
PathogenesisInfection
Dendritic cells/Macrophages
Draining lymph nodes (Replication)
Tissue invasion
Bloodstream (Dissemination)
Inflammatory cells
Vasoactive mediators (TNF-α, NO, MCP-1)
Recovery
Capillary endothelial cell permeabilty
Plasma leakage/haemorrhage/shock
Recovery Death
Tissue damage (liver, kidney)
Viraemia
Secondary viraemia
Pathogenesis
Pathogenesis
Pathogenesis• Mechanism of endothelial dysfunction
Pathogenesis• Summary of pathogenesis of VHFs
Pathogenesis
• Major pathogenic mechanisms
Depletion of hepatic coagulation factors
Cytokine storm (TNF-α, IL-10, IL-1Ra, TRAIL, etc)
Increased vascular permeability
Complement activation, and DIC
Impaired innate immune response from non-lytic
viral replication
Thrombocytopenia & Inhibition of Platelet Fn.
Pathogenesis• Pathogenic mechanisms proposed for VHFs
Virus Leukopenia/
Immunesuppr
ession
Thromboc
ytopenia
Platelet
altered
function
Reduced
coagn
factors
DIC Endothelial
dyfn
YF + + ? + + +LF + +/N + - - +EHF + + + + + +MHF + + + + + +DHF + + + + + +CCHF + + ? + + +RVF + + ? + + +
Pathogenesis
• Pathobiological and Clinical Aspects of VHFs
VHF I.P
(day
s)
Onset Blee
ding
Rash Jaundi
ce
Heart Lung Kidney CNS Eye
YF 3-6 Abrupt +++ 0 +++ ++ + ++ ++ 0
LF 5-16 Gradual + + 0 ++ + 0 + 0
EHF 2-21 Abrupt ++ +++ + ++ + + + +
MHF 2-21 Abrupt ++ +++ + ++ + + + +
DHF 3-15 Abrupt ++ +++ + ++ + 0 + 0
CCHF 3-12 Abrupt +++ 0 ++ + + 0 + 0
RVF 2-5 Abrupt ++ + ++ + 0 + ++ +
Pathogenesis• Natural history
Clinical features
• Spectrum from mild or asymptomatic infection
to severe vascular permeability with shock,
multi-organ system failure and death
• Clinical presentation may differ for each viral
HF as it progresses
• Distinct phases of disease and recovery
• Biphasic illnesses with quiescent period of
days (YF and DHF)
Clinical features
Incubation period days to weeks
Fever and
Constitutional symptoms:
• General malaise
• Anorexia
• Headache
• Myalgia
• Arthralgia
• Sore throat
• Chest or retrosternal pain and lumbosacral pain
Clinical features
GIT features: Nausea/Vomiting, Abdominal pain/tenderness, Diarrhoea (may become bloody in later stages), Constipation
Conjunctival injection/haemorrhage
Skin rash: Morbilliform, Maculopapular, Petechial, Ecchymotic
Orthostatic hypotension
Neck pain/stiffness, retro-rbital pain/photophobia (RVF)
Clinical features
End of first week (vascular instability)
Facial flushing
Oedema
Bleeding
Haematemesis, melena/haematochezia, metrorrhagia, petechiae, purpura, epistaxis, bleeding from gums, venepuncture sites
Internal bleeding from GIT
Haemoptysis and haematuria are infrequent
Hypotension/shock
Proteinuria
Clinical features
CNS manifestations (end-stage disease)
• Disorientation
• Tremor
• Gait anomalies
• Convulsions
• Hiccups
Renal failure (end-stage disease)
Spontaneous abortion/vaginal bleeding, maternal/fetal mortality ~100% in 3rd trimester
Clinical features
• Persistent myalgia
• Arthralgia
• Anorexia
• Weight loss
• Alopecia
• Orchitis
• Irritability
• Memory changes
No permanent sequelae
in most cases
Depression
Post-traumatic stress
Social stigmatization
Convalescence (up to a year)
Differential diagnosis
• Initial misdiagnosis of more familiar
syndromes is common
• Malaria and bacterial septicaemia, most
common
• Possibility of co-infection should be
considered
Differential diagnosis
• Features making VHF less likely:
o Haemorrhage in the first few days of illness
o Conjunctival injection/sub-conjunctival
haemorrhage accompanied by itching
o Jaundice on presentation (except YF)
o Prominent pulmonary symptoms
o Response to antibiotics
Differential diagnosis
Viruses:
• Inluenza
• Viral hepatitis (hp.A, B, E, EBV and CMV)
• Herpes simplex or varicella-zoster (fulminant)
• HIV/AIDS
• Measles
• Rubella
• Haemorrhagic or flat smallpox
• Alphavirus infection (chikungunya, o’nyong-nyong)
Differential diagnosis
Bacteria:
• Typhoid fever
• Bacillary dysentery
• Meningococcaemia
• Staphylococcaemia
• Septic abortion
• Septicaemic plague
• Streptococcal pharyngitis
• PTB (advanced)
• Acute abd. emergencies
• Tularaemia
• Pyelonephritis
• Post-infectious GN
• Anthrax (inhalation or GI)
• Relapsing fever
• Leptospirosis
• Rickettsia
• Q fever
• Ehrlichiosis
Differential diagnosis
Parasites:
• Malaria
• Amoebiasis
• Giardiasis
• African tripanosomiasis
(acute stages)
Non-infectious
• Heat stroke
• ITP/TTP
• Acute glaucoma
• Haem. malignancies
• Drug sensitivity/overdose
• Chemical poisoning
• Haematoxic snake bite
envenomation
Diagnosis
Clinical Diagnosis
Laboratory Diagnosis
Case Definition
Diagnosis
Clinical Diagnosis
History of illness
Detailed epidemiological history
Physical examination
Preliminary basic laboratory results
Diagnosis
Clinical Diagnosis
Clinically compatible syndrome
Fulfills any epidemiologic linkage criteria
• High index of suspicion for persons in high-risk occupations: abattoir workers, veterinarians, farm workers/hunters/taxidermists.
• Acts of bioterrorism must be considered
• Alternative diagnoses should always be aggressively sought
Diagnosis
• Wbc & diff; ESR
• Hb/Hct
• Platelet count
• BUN/creatinine
• AST, ALT, lactate
• Blood gas
• Coagn studies (PT/PTT,
fibrinogen, FDP, D-dimer)
• Urinalysis
• Blood culture
• Stool culture
• Thick/thin blood smears
• Rapid test for malaria
• Assay for Salmonella
• Indicated Clinical Laboratory Tests
Diagnosis
Laboratory Diagnosis
• VHF still suspected after initial work-up/lab tests
• Specialized laboratory testing
ELISA
RT-PCR
Cell culture
IFA
Immunohistochemical staining of formalin-fixed tissue: skin, liver, spleen (Post-mortem diagnosis)
Diagnosis
Laboratory Diagnosis
• No test can reliably diagnose VHF before onset of illness
• Test of contacts/asymptomatic persons not recommended
Acute febrile stage
• Identify virus/virus antigen/nucleic acid
• Prognostic value
• Samples: serum, throat washings, urine, CSF, breast milk
ELISA antigen tests
RT-PCR
Multiplex PCR assays
Cell culture (high containment facility; 2–10 days)
Diagnosis
o False negative
Limitations: of the various lab assays
Inhibitory substances in the blood
• Repeat in 1-2 days and, if necessary, again in convalescence, if high clinical suspicion
• Discard diagnosis if virus, antigen or nucleic acid cannot be detected during first 7 days of illness and IgM is negative
o False-positive
Diagnosis
Laboratory Diagnosis
Sub-acute and convalescent stages
• IgM antibody (sub-acute stage)
• IgG antibody (convalescent stage)
• ELISA or IFA
• Antibody seroconversion (4-fold increase in
titre) retrospectively diagnose acute disease
Diagnosis
Case Definition
2011 Case Definition
Clinical Criteria
Laboratory Criteria
Epidemiologic Linkage
Diagnosis
Fever >40°C
One or more of:Severe headache
Muscle pain
Erythematous maculopapular
rash on trunk with fine
desquamation after 3-4 days
Vomiting
Diarrhea
Pharyngitis (LF)
Abdominal pain
Bleeding unrelated to injury
Retrosternal chest pain (LF)
Proteinuria (LF)
Thrombocytopenia
Clinical Criteria• Illness with ACUTE ONSET with:
Diagnosis
Laboratory Criteria• One or more of:
Detection of VHF viral antigens in blood by ELISA antigen detection
VHF viral isolation in cell culture of blood/tissues
Detection of VHF-specific genetic sequence by RT-PCR from blood or tissues
Detection of VHF viral antigens in tissues by immunohistochemistry
Diagnosis
Epidemiologic Linkage• One or more of the following exposures within 3wks:
Contact with blood/body fluids of VHF px
Residence in/travel to VHF endemic area
Work in lab that handles VHF specimens
Work in lab that handles bats, rodents, primates from endemic areas
Exposure to semen of confirmed acute/convalescent case of VHF in 10wks of the person's symptom onset
Diagnosis
o Case Classification
• Suspected
Clinical criteria
Epidemiologic linkage criteria.
• Confirmed
Clinical criteria
Laboratory criteria.
Management and Treatment
• Routine universal precautions
• Consultation with infectious disease specialists or clinicians with experience when diagnosis is suspected
• When to ‘sound the alarm’ of VHF is case-by-case decision
• All cases of confirmed VHF should be reported to
o Government health authorities
o WHO
Management and Treatment
• In Nigeria
Access to basic lab tests for broad range of dx
in diff. dx of VHF is limited
Empiric treatment to cover usual range of
infectious agents
Admission to isolation ward based on
nonspecific clinical/epidemiological features
On-site specialized diagnostics advocated
Management and Treatment
General supportive measures
Antiviral drugs
Antibody therapy
Immune modulators
Coagulation modulators
Management of convalescence
Management and Treatment
General supportive measures
Fluid Management
• Aggressive fluid replacement
Crystalloids (Ringers lactate or normal saline)
Vasopressors (dopamine or norepinephrine) to maintain CVP bt 8-12 mmHg or MAP >65 mmHg in adults
Dobutamine
Peritoneal/haemo-dialysis (renal syndrome)
Management and Treatment
Blood Products and Management of DIC
Packed rbc to maintain Hct > 30%
Platelet concentrate (1-2 U/10 kg) if platelet count <50,000/µL (<20 000/µL without bleeding)
FFP (15-20 mL/kg) if bleeding is present & fibrinogen levels <100mg/dL
Fibrinogen concentrates (total dose 2-3g) or cryoprecipitates (1U/10 kg)
VitK if underlying malnutrition or liver dx
Management and Treatment
Antibiotics and/or antiparasitics
Pain control and ulcer prophylaxis
Management of seizures
Nutrition
Management of pregnant patients
Uterine evacuation (extreme caution)
Lab parameters should be monitored closely
Management and Treatment
Antiviral drugs
Ribavirin
• Guanosine analogue
• Lethal mutagenesis
Efficacious in treatment of LF
Used for CCHF
• Not efficacious for EHF/MHF
Management and Treatment• Ribavirin Therapy
Indication Route Dose Interval
Treatment IV
IV
IV
30mg/kg
(max.2g)
15mg/kg
(max.1g)
7.5mg/kg
(max.500mg)
Loading dose, followed by:
Every 6hrs for 4days,
followed by:
Every 8hrs for 6days
Prophylaxis PO
PO
35mg/kg
(max.2.5g)
15mg/kg
(max.1g)
Loading dose, followed by:
Every 8hrs for 10days
Management and Treatment
Ribavirin
• Side-effect: haemolytic anaemia
• Contraindications (relative)
o Severe anaemia or haemoglobinopathy
o CAD
o Renal insufficiency
o decompensated liver disease
o breast-feeding
o Known hypersensitivity
o Pregnancy
Other antiviral drugs (Experimental therapies)
Management and Treatment
Antibody Therapy
• Severe/refractory cases when ribavirin is not
an option
Immune Modulators
• Corticosteroids if adrenal insufficiency
Coagulation Modulators (experimental)
Management and Treatment
Abstinence/condom use
for 3 months
Separate toilet facilities
Regular hand-washing
Avoid breast-feeding
Warm packs
Acetaminophen/NSAID
Cosmetics; hair-growth
stimulants
Anxiolytics/antidepressants
Nutritional supplements
Psychological counselling
Management of Convalescence
Prevention
Patient isolation
Personal Protective Equipment (PPE)
Nursing precautions
Contact tracing
Post-exposure prophylaxis
Environmental shedding and disinfection
Vaccines
Reservoir/vector control
Ebola virus disease
• First appeared in 1976 in 2 villages in Central Africa, the 2nd near Ebola river
• Index case 2yr-old boy Emile died on 6 Dec.2013, Guinea.
• WHO reported outbreak: 25, March 2014
• Countries affected: Nigeria, Senegal, Guinea, Liberia, Sierra Leone, US, Spain.
• By 14th October, 2014:
9,216 suspected cases; 4,555 deaths
4,995 cases; 2,729 deaths lab confirmed
• Average case fatality rate: 50%
Ebola virus disease
Country reports fall into 2 categories:
Widespread and intense transmission (Guinea,
Liberia, and Sierra Leone)
Initial case/cases, or localized transmission
(Nigeria, Senegal, Spain, USA)
• On August 8, WHO Director-General declared
this outbreak a Public Health Emergency of
International Concern
Ebola virus disease
• 20 July, 2014 first case in Nigeria Patrick
Sawyer (from Liberia); died, July 25.
• Cases in Nigeria
• Case fatality rate: 40%
• 891 contacts have now completed 21-day
follow-up (362 in Lagos, 529 in Port Harcourt)
CASE DEFINITION CASES DEATHS
Confirmed 19 7
Probable 1 1
Suspected 0 0
All 20 8
Ebola virus disease
5 species:
• Zaire ebolavirus (1976) - in present outbreak
• Sudan ebolavirus (1976)
• Côte d'Ivoire ebolavirus (1994; also known as
Tai Forest ebolavirus)
• Reston ebolavirus (1994)
• Bundibugyo ebolavirus (2007)
Ebola virus disease• Life cycle of the Ebolavirus
Ebola virus disease
Viral Proteins
Nucleoprotein (NP)
Polymerase cofactor (VP35)
Matrix protein (VP40)
soluble GP (sGP), GP1,2
Transcription activator (VP30)
Secondary matrix protein (VP24)
RNA-dependent RNA polymerase (L)
Ebola virus disease
• Entry via: conjunctiva and oropharynx, or injured skin, eating of freshly killed bats
• Extensive replication in lymph nodes, spleen, liver
GP1,2-mediated entry mechanisms:
Endocytosis
Macropinocytosis
sGP:
Anti-inflammatory
Endothelial barrier protector function
Induces cytopathic effects
Ebola virus disease
GP1,2 and VP40
Activate endothelial cells to express ICAM-1, VCAM-1, and E-selectin
Induce macrophages to secrete TNF-α, IL-6, IL-8, GPO-α
VP35 and VP24 inhibit IFN activity
• EV inhibits dendritic cell maturation/cytokine production, with reduced T cell proliferation
• Decreased CD4/CD8 T lymphocytes by apoptosis mediated by Fas/FasL
Ebola virus disease
• Multifocal necrosis occurs most severely in
liver, spleen, kidneys, testes, and ovaries
• Survivors develop IgG mainly against NP
early, and VP40
• Thereafter cytotoxic T cells are activated
• Terminally ill patients never develop IgG and
only 1/3 mount weak IgM response
Ebola virus disease• Replication cycle of EV
Ebola virus disease
• Clinical features
• Incubation period: 5 days (2-21 days)
Early features
Sudden onset fever, headache, myalgia, sore throat, extreme fatigue
Conjunctivitis
Relative bradycardia
Nausea/vomiting, abdominal pain and watery diarrhea
Perifollicular, non-itching, maculopapular rash (5th day)
Ebola virus disease
Haemorrhagic manifestations (5-7th day), in ˂50%:
Epistaxis/gum-bleeding
Haematemesis/melaena
Petechiae/ecchymoses
Haemorrhages from needle sticks
Visceral haemorrhagic effusions
Dehydration, prostration; ghost-like facial expression
Hepatosplenomegaly, oedema, orchitis, scrotal/labial reddening, myocarditis and pancreatitis
Ebola virus disease
Poor prognosis is marked by:
Haemorrhagic signs
Oliguria/anuria; shock
Tachypnoea
Neurological symptoms: confusion or coma
Death due to shock occurs 6-9 days after onset
Abortion is a common consequence
Recovery may last for wks: weakness, arthralgia, uveitis, orchitis, hearing loss
Ebola virus disease
• Oral bleeding • Rectal bleeding
Ebola virus disease
Other Lab. findings
• Low wbc
• Low platelet count
• Prolonged PT/aPTT
• Low fibrinonogen
• High FDP
• High liver enzymes
• Renal failure
Diagnosis
• RT-PCR assay
• Antibody-capture ELISA
• Antigen-capture detection tests
• Serum neutralization test
• Electron microscopy
• Cell culture.
• No test can detect infection in incubation period
Ebola virus disease• Case classification criteria
CLASSIFICATION CRITERIA
Suspected Sudden onset of high fever and contact; or
Sudden onset of high fever and at least 3 of:
headache, vomiting, anorexia, diarrhoea,
lethargy, abdominal pain, muscle/joint
aches, difficulty swallowing, breathing
difficulty, or hiccup; or
Any person with unexplained bleeding; or
Sudden, unexplained death
Probable Suspected case or death from suspected EVD
with epidemiological link to confirmed case but
no lab confirmation
Confirmed Probable or suspected case with lab confirmation
Non-case Suspected or probable case with a -ve lab result
Ebola virus disease
Management
• Isolation
• No specific antiviral therapy
• Supportive care
Rehydration with oral or intravenous fluids
Treatment of specific symptoms
• Activated protein C (experimental)
• rNAPc2 (completed phase 1 trial)
Ebola virus disease
o PEP and vaccine
(undergoing trials)
Vesicular stomatitis
virus vectored vaccine
DNA plasmid vaccine
• Proper case management
• Surveillance
• Contact tracing
• Good laboratory service
• Safe burials
• Social mobilisation
Prevention and control
Ebola virus disease
Focus of risk reduction measures
Reducing risk of wildlife-to-human transmission
Reducing risk of human-to-human transmission
Outbreak containment measures
Controlling infection in health-care settings
WHO response
Nigeria response
Conclusion
• VHFs are emerging infectious dxs caused by ssRNA viruses belonging to 4 families
• 7 have been shown to be present in Nigeria either by case identification or serological evidence
• They cause uniformly severe infections with high fatality rates to mostly asymptomatic infections
• Hallmark is vascular instability
• Important to spot due to public health implications
• Minimizing contact is essential
• Nigeria successfully contained EVD
• Efforts must continue to prevent re-emergence in the country and to contain the disease in worst hit areas
THANK YOU
FOR LISTENING
References
• David Mabey et al, Principles of Medicine in Africa, 4th Edition; 2013; Ch.34
• Jeremy Farrar et al; Manson’s Tropical Diseases, 23rd Edition; 2014; Ch.16
• http://wwwnc.cdc.gov/travel/yellowbook/2014/chapter-3-infectious-diseases-related-to-travel/viral-hemorrhagic-fevers
• https://www.gov.uk/lassa-fever-origins-reservoirs-transmission-and-guidelines; Lassa fever: map of Nigeria 2012 and 2013 outbreaks
• WHO. International Travel and Health: Situation as on 1 January 2010. Geneva: WHO; 2010; Appendix 1a: Yellow Fever countries at risk, 2008
• http://www.flutrackers.com/forum/showthread.php?t=181234; reported outbreaks of Lassa fever as of 16th March, 2012
• http://www.cdc.gov/vhf/lassa/resources/distribution-map.html
• http://www.health.gov.ng/index.php/news-media/9-uncategorised/162-health-minister-debunks-outbreak-of-ebola-virus-in-nigeria-says-is-dengue-fever
References
• Daily Trust (Abuja) 2 APRIL 2014Nigeria: Govt - We Have Case of Dengue Fever, Not Ebola Virus
• Umoh et al; Prevalence of antibodies to Crimean haemorrhagic fever-Congo virus in cattle in northern Nigeria; Int. J. Zoonoses. 1983, Dec; 10(2):151-4
• Tomori O et al; The American journal of tropical medicine and hygiene;1988 Mar; 38(2): 407-10. Viral hemorrhagic fever antibodies in Nigerian populations. OLALEYE et al; Rev. sci. tech. Off. int. Epiz., 1996,Sept. 15(3),923-935; Rift Valley fever in Nigeria: infections in humans
• Oyewale Tomori; Rift valley fever virus infection in man in Nigeria; Journal of Medical Virology; Volume 5, Issue 4, pages 343–350, 1980
• Overview of the epidemiological situation of yellow fever in Africa; The yellow fever situation in Africa and South America in 2004, Weekly Epidemiological Record. Vol. 80, 29, 2005 249–256; http://www.who.int/wer
• Epidemiological data 2000-2004; http://www.who.int/csr/disease/yellowfev/surveillance/en/#figures
References
• http://www.thetraveldoctor.com/nigeria-medical-alert; CASES OF YELLOW FEVER IN NIGERIA, Mar 01, 2013
• D. E. Carey et al; DENGUE VIRUSES FROM FEBRILE PATIENTS IN NIGERIA, 1964-68; The Lancet, Volume 297, Issue 7690, Pages 105 -106, 16 January 197
• David-West TS et al, (1974); Seroepidemiology of Congo virus (related to the virus of Crimean haemorrhagic fever) in Nigeria. Bull WHO 51: 543-546
• Idris A. N. et al; Sero-prevalence of dengue type-3 Virus among patients with febrile illnesses attending a tertiary hospital in Maiduguri, Nigeria; International Journal of Medicine and Medical Sciences; Vol. 5(12), pp. 560-563, December 2013
• http://ci.vbi.vt.edu/pathinfo/pathogens/Rift_Valley_Fever_virus.html
• http://vhfc.org/lassa_fever/virology
• Pathogenesis of the Viral Hemorrhagic Fevers, Annual Review of Pathology: Mechanisms of Disease; 2013; Vol. 8: 411-440
• https://microbewiki.kenyon.edu/index.php/Infection Mechanism of Genus Ebolavirus
References
• www.medscape.com/Clinical Aspects of Marburg Hemorrhagic Fever; Pathology & Pathophysiology; fig.3: Marburg hemorrhagic fever pathogenesis model
• http://wwwn.cdc.gov/ National Notifiable Diseases Surveillance System (NNDSS); 2011 Case Definition
• http://en.wikipedia.org/wiki/File:EbolaCycle.png
• http://virologytidbits.blogspot.com/2014/03/Molecular aspects of Ebola and other Filoviruses
• WHO: EBOLA RESPONSE ROADMAP UPDATE; 17, October, 2014
• http://www.who.int/mediacentre/factsheets/fs103/en/Ebola virus disease; September, 2013
• http://wwwnc.cdc.gov/travel/notices/watch/ebola-nigeria
• http://en.wikipedia.org/wiki/Ebola virus epidemic in West Africa