Transcript No Slide Title - National Orthopaedic Hospital

THE LASSA FEVER STORY
Abdulrazaq G. Habib
Infectious & Tropical Diseases Unit
College of Health Sciences
Bayero University & Aminu Kano Teaching Hospital
Kano, Nigeria
(Member WHO-Nigerian Immunization Technical Advisory Group)
Bayero University Kano
Nigeria
President
www.nigerianidsociety.com
Fauci A (2001). Global emerging and reemerging infectious diseases
Lassa
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Lassa fever
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12 Jan 1969- 1st recognised case an American missionary nurse in Lassa,
NE- Nigeria
25 Jan 1969- Air lifted to Evangel. Hospital Jos, N. Nigeria
26 Jan 1969- Pt was cared by two american nurses but died that day
One of the two caring nurses fell sick after an 8d IP and died after an illness
lasting 11d
20 Feb 1969- Head Nurse of the hospital where autopsy for 1st case was
done fell sick
Pt evacuated to USA by air on a commercial Boeing 707, separated with
curtain only
Pt recovered after severe protracted illness at ICU of Columbia University
NY
Lassa fever
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A virus was isolated and later named Lassa at Yale Arbovirus Research
(YAR) Unit
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9 Jun 1969- One of YAR virologists fell ill and survived only as a result of an
immune plasma transfusion donated by the surviving third case
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30 Nov 1969- A Laboratory technician at YAR fell ill and died
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Jan-Feb 1970- a devastating hospital outbreak at Vom and Jos: Outbreak
affected 28 patients with 12 deaths, including the American doctor who first
identified the disease and did autopsies
General Facts
• Viral hemorrhagic fever caused by the Arenavirus
Lassa
• Transmitted from rodents to humans
• Discovered in Nigeria, 1969
• Endemic in portions of West Africa
• Seasonal clustering: Late rainy and early dry season
• Affects all age groups and both sexes
Arenaviridae
• Name derived from “arenosus” (Latin “sandy”) describing
appearance of virions on examination by electron microscopy
• Enveloped virus, round or pleomorphic, 50-300 nm in diameter
• Single-stranded genome divided into 2 RNA segments: small
(~3.4 kb) and large (~7.1 kb)
• 2 genes on each segment, arranged in unique “ambisense”
orientation, encoding 5 proteins
• Inactivated by:
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heating to 56 F
pH<5.5 or >8.5
UV/gamma irradiation
detergents
Arenaviridae
• Arenaviruses associated with human disease
Virus
Lassa
Junin
Machupo
Guanarito
Sabia
LCMV
Origin of Name
Town, Nigeria
Town, Argentina
River, Bolivia
Area, Venezuela
Town, Brazil
Clinical disease
Year
1969
1957
1962
1989
1990
1933
Distribution
West Africa
South America
South America
South America
South America
Worldwide
Lassa Virus
Image source: C.S. Goldsmith and M. Bowen (CDC).
Epidemiology
• Endemic in areas of West Africa, including Nigeria,
Liberia, Sierra Leone, and Guinea
• Estimated 300,000-500,000 infections/year, with 5000
deaths
• Rodent-to-human transmission (the “multimammate rat”,
Mastomys species-complex)
• Secondary human-to-human transmission with the
potential for nosocomial outbreaks with high case-fatality
• CDC undertook serological studies in Sierra
Leone
• 2.2 cases/1000 inhabitants
• Some areas had seroprevalence of 52%
• Most infections benign
• 200,000-300,000 cases p.a.
• 5,000-10,000 deaths p.a.
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LASSA FEVER IN WEST AFRICA
Fichet-Calvet & Rogers 2009
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States that reported Lassa fever 2007/2008
Lassa
fever
2007/08
Current Nigerian epidemic: Kano
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Started Nov 2015
Two patients admitted 3rd / 4th December
Diagnosis came out Lassa Fever
112 people had contacted them, 75% HCW
4 had symptoms, positive sera and on Ribavirin
Unguwa Uku, Tiga and Bunkure
38 being monitored now
Rijiyar Lemo?
(A case in 2012?)
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• 2015 Wk 42: 337 cases, 13 lab confirmed, 7
dead, CFR2.08%
• 2014: 974 cases 95 lab confirmed, 33 dead,
CFR 3.39%
• Taraba, Rivers
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Epidemiology in Nigeria
• Many cases of Lassa fever are un
accounted
• Poor lab support
• Inadequate surveillance systems
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Tarauni
Kura
Bebeji
Bunkure
Fagge
Dala
Gwale
Kumbotso
KMC
Gwarzo
Shanono
T/Wada
Rano
Total
Description
New Cases
New Confirmed
New Probable
New Suspected
Cumulative Cases
Total Confirmed
Total Probable
Total Suspected
Total
Total No. currently in isolation
Deaths
Newly Reported on 18th Jan 2016
Total Deaths in Confirmed cases
Total Deaths in Probable cases
Total Deaths in suspected cases
Total Deaths
Contacts
New Contacts listed on 18th Jan 2016
Cumulative contacts listed
Contacts currently under follow up
Contacts seen on 18th Jan 2016
Contacts who completed 21 days FU
Contacts lost to follow Up
Contact Dropped after negative result
Laboratory
Specimen collected on 18th Jan 2016
Specimen Pending testing
Total Specimen tested
Garun
Mallam
KANO DATA AS AT 18th JANUARY 2016
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
2
0
5
7
0
0
0
1
1
0
0
0
1
1
1
0
0
1
1
0
0
0
1
1
0
0
0
0
0
0
0
0
1
1
0
0
0
0
0
0
0
0
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
0
0
0
1
1
0
0
0
1
1
0
2
0
14
16
1
0
2
0
1
3
0
0
0
1
1
0
0
0
0
0
0
0
0
1
1
0
0
0
1
1
0
0
0
0
0
0
0
0
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
1
0
0
0
0
0
0
0
2
0
7
9
0
45
0
0
45
0
0
0
115
11
4
78
7
26
0
29
0
0
24
0
5
0
34
11
0
23
11
0
0
7
0
0
7
0
0
0
4
4
0
0
4
0
0
14
14
7
0
7
0
0
12
12
11
0
1
0
0
7
7
3
0
4
0
0
2
1
1
1
0
0
0
4
0
0
4
0
0
0
6
0
0
6
0
0
0
0
0
0
0
0
0
0
27
27
0
0
27
0
0
306
87
26
188
61
31
0
0
6
0
0
1
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
1
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Known Distribution of Mastomys
MASTOMYS
DISTRIBUTION
LASSA 1969
Reservoir
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Rodent Reservoir
• Mastomys species
complex
• Taxonomy still unclear
– M. huberti: more
common in
peridomestic habitat
– M. erytholeucus: more
common in brush
habitat
– Others
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Transmission
• Rodent-to-human:
– Inhalation of aerosolized virus
– Ingestion of food or materials contaminated
by infected rodent excreta
– Catching and preparing Mastomys as a food
source
Transmission
• Human-to-human:
– Direct contact with blood, tissues,
secretions or excretions of infected
humans
– Needle stick or cut
– Inhalation of aerosolized virus
Pathogenesis
• Endothelial cell damage/capillary leak
• Platelet dysfunction
• Suppressed cardiac function
• Cytokines and other soluble mediators of
shock and inflammation
Clinical Aspects
• Incubation period of 5-21 days
• Gradual onset of fever, headache, malaise and other non-specific
signs and symptoms
• Pharyngitis, myalgias, retro-sternal pain, cough and
gastrointestinal symptoms typically seen
• A minority present with classic symptoms of bleeding, neck/facial
swelling and shock
• Case fatality of hospitalized cases: 15-20%
• Particularly severe in pregnant women and their offspring
• Deafness a common sequela
Clinical Signs and Symptoms
Fever
Headache
Arthralgias/Myalgias
Retro-sternal Pain
Weakness
Dizziness
Sore throat/Pharyngitis
Cough
Vomiting
Abdominal Pain/Tenderness
Diarrhea
Conjunctivitis/Sub-conjunctival
Hemorrhage
Chills
Deafness
Lymphadenopgathy
Bleeding
Confusion
Swollen Neck or Face
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Percent
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70
80
90
100
Lassa Fever in Pregnancy
• Increased maternal mortality in third trimester
(>30%)
• Increased fetal and neonatal mortality (>85%)
• Increased level of viremia in pregnant women
• Placental infection
• Evacuation of uterus improves mother’s chance
of survival
Sensorineural Hearing Deficit in
Lassa Fever
• Typically appears during early convalescence
• Not related to severity of acute illness
• Occurs in one-third of cases
• May be bilateral or unilateral
• May persist for life in up to one-third of those
affected
Lassa Fever in Children and Infants
• Significant cause of pediatric hospitalizations
in some areas of West Africa
• Signs and symptoms most often similar to
adults
• “Swollen Baby Syndrome”
- Edema/Anasarca
- Abdominal distension
- Bleeding
- Poor prognosis
Differential Diagnosis of
Lassa Fever
• Malaria
• Bacterial sepsis
• Typhoid fever
• Bacterial meningitis
• Streptococcal
pharyngitis
• Arboviral infection
• Leptospirosis
• Enterovirus infection
• Anicteric hepatitis
• Bacterial or viral
conjuctivitis
Diagnostics
• Clinical diagnosis often difficult
• ELISA (Enzyme-linked immunosorbent
assays) for antigen, IgM, and IgG
• As research tools:
– Virus isolation
– Immunohistochemistry (for post-mortem
diagnosis)
– RT-PCR (Reverse transcription-polymerase
chain reaction)
Treatment
• General support
Fluids and electrolytes
Antipyretics
Oxygen
Intensive care
(Antibiotics)
• Ribavirin
• Infection control
Barrier nursing
• Report!
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Treatment
• Supportive measures
• Ribavirin
– Most effective when started within the first 6 days
of illness
– Major toxicity: mild hemolysis and suppression of
erythropoesis. Both reversible
– Presently contraindicated in pregnancy, although
may be warranted if mother’s life at risk
– Does not appear to reduce incidence or severity
of deafness
Ribavirin dose
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Loading dose 2g
1g 6 hourly x 4d
500mg 6 hourly days 5-10
30mg/kg, 15mg/kg, 7mg/kg
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Side effects
• Fatigue, headache, alopecia, fever, anxiety,
N. V, D, impaired concentration
• Haemolytic anaemia
• Neutropenia
• Thrombocytopenia
• Embryocide
• Suicide ideation
• Pregnancy benefits Vs risks
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• Hypersensitivity
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Associated with Poor Prognosis in
Lassa Fever
• High viremia
• Serum AST level >150 IU/L
• Bleeding
• Encephalitis
• Edema
• Third trimester of pregnancy
Nosocomial Lassa fever in Nigeria
Fisher-Hoch SP, Tomori O, Nasidi A et al. BMJ 1995; 311: 857-9
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Two hospital outbreaks in Imo state
34 patients
6 nurses; 2 surgeons; 1 physician
Diagnosis: All clinically consistent; 11 serological; 5 virus isolation
Attack rate = 55%
22 deaths (65%)
Likely cause: Parenteral drug rounds and sharing of needles
Inference: Elucidates the high price of poor medical practice
Key points: High priority must be given to education of medical staff,
equiping hospitals, promoting infection control practices and use of
guidelines for safe operation of clinics and hospitals in developing
countries.
Prevention
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Early patient identification
Barrier nursing
Universal precautions
PPE
Waste disposal
Rodent control
Rodent hunting/ eating
No vaccine
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Prevention and Control
• Village-based programs for rodent control
and avoidance
• Hospital training programs to avoid
nosocomial spread: barrier nursing manual
• Diagnostic technology transfer
• Specific antiviral chemotherapy (ribavirin)
Rodent Control
• Proper storage of food in rodent-proof
containers
• Cleaning around homes
• Trapping and killing rodents with proper and
safe disposal of carcasses
• Avoid rodents as a food source
Negative Pressure Isolation Room
Natural Ventilation
Cohorting Room
1 meter
Use PPE on patient contact
Put on and Remove PPE
PAPRs are available
Ongoing Lassa Fever Research in
Guinea, West Africa
• Natural history of disease
– Where it came from
– How clinical course progresses
– Whom it affects
• Diagnosis: Clinical/Laboratory
• Immunopathogenesis
• Treatment
• Rodent population dynamics
• Prevention and control
Collaboration between CDC/SPB and the Guinean Institute for Research and Applied Biology
Infections as Strategic and Security issue:
Daniel Defoe’s Journal – A Visitation of The Plague
‘It was indeed, that man withered like grass and that his brief
earthly existence became a fleeting shadow. Contagion was
rife in all our streets and so baleful were its effects, that the
church yards were not sufficiently capacious to receive the
dead. It seemed for a while as though the brand of an
avenging angel had been unloosed in judgement ….’
‘..panic spread over the city of London. Trapped by poverty, a
gullible populace became prey to an army of astrologers,
charlatans and quack doctors who offered false promises of
hope in the face of impending horror’
Distribution of Reported Epidemics in Nigeria from 2003 – 2007 and Jan 2008
KEY
Cholera/Gastro
Enteritis
2003
2004
2005
2006
2007
CSM
NE
Measles
Yellow Fever
2007/2008
2004
2005
Lassa Fever
2003
2003
2003
2006
2004
2004
2005
2005
2006
2006
2007/2008
2007/2008
NE: No Epidemics reported
2007
AI Human
2007
“Humanity has but three
great enemies: fever,
famine and war; of
these by far the greatest,
by far the most terrible,
is fever”
William Osler
Thank you