Lassa Fever Edited

7/31/2019 Lassa Fever Edited

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OUTLINE Introduction

History

Epidemiology

The Recent Outbreak

Mastomys natalensis

The Lassa virus Pathogenesis

Clinical Features Pathology

Diagnosis

Treatment

Prevention and Control

Conclusion


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INTRODUCTION

Lassa fever is a viral haemorrhagic disease caused bythe Lassa virus

The virus was first identified in 1950 but later namedin 1969 after the town where the first outbreakoccurred

Lassa is a town in Borno state , Yedesram valley, near

the Lake Chad Laura West was a missionary nurse who had been

resident in Lassa for the past 4 years


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HISTORY Laura developed a sudden onset of fever, back pain and

sore throat, she was manged by Dr Hammer the onlydoctor in Lassa.

The doctor was worried about her deteriorating clinicalstate as she developed petechiae, anuria even after she hadbeen given CQ and procaine penicillin

When she later developed convulsion , she was flown to

Evangel hospital in Jos, then known as Bingham Memorialhospital

A nurse , by name Charlotte Shaw, at the hospital had afinger prick at home and covered her thumb with a gauze.


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HISTORY She used her finger to clean Laura s throat and later

became ill, she died on the 11th day of her illness

Postmortem was carried out on her by Dr Troupe,

assisted by Penny Pineo, a head nurse. Blood andtissue samples were taken for studies

A week later, Penny Pineo became ill ,his conditiondeteriorated over 2 weeks. He was flown to New York

while his specimen was also sent to Yale arboviralresearch Lab

The Lassa virus was isolated in the lab by Drs, Down,Jordi, Casal and Sonja Buckley


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HISTORYJordi Casal came down with Lassa and was given

antiserum from Penny pineo, he survived.

A patient on admission as well as her mother and hersister became infected. Four health care workers alsosuddenly became ill with similar symptoms.

Dr Troup while carrying out autopsy on one of the staff

that died, accidentally cut herself, she became ill anddied after 10 days .

Her death brought the number of cases to 19 andmortality to 10.


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HISTORY The disease became almost forgotten till 1989 when a

family was nearly erased completely in IhumudumuEkpoma.

The diagnosis was made in the United States throughtissues taken at post mortem when a team came fromthe CDC, Atlanta Georgia

The team visited the family and the then nearestMedical school. ( the University of Benin/University ofBenin Teaching Hospital).


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HISTORY For the second time Lassa was again forgotten till 1993

when, with the inception of the located near Ekpoma. A strange pattern of disease was noticed among some

patients admitted at Irrua Specialist Teaching . It started with fever ,the patients later became anuric, hadbleeding diasthesis and eventually died.

Those that had dialysis survived while some people becamedeaf on recovery.

Blood samples were sent to Prof Tomori in UniversityCollege Hospital, Ibadan. Information arrived later thatthe strange disease was Lassa Fever

From then on clinicians have become more vigilant and ahigher index of suspicion has since been maintained.


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EPIDEMIOLOGY

Endemic in West Africa countries and has beenreported in Nigeria, Liberia, Sierra Leone and Guinea

Casesof Lassa fever have been imported to Europe.

300,000 to 500,000 cases of Lassa fever and 5000

deaths occur yearly across West Africa. Lassa virus antibodies were detected in

21.3% of serum samples from Nigeria.

8-22% in Sierra Leone 4-55% in Guinea.

E i


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Epi .cont

Rodent to human transmission occurs majorly throughmultimammate rats (Mastomys natalensis) whichserves as reservoir for the virus.

a) Ingestion of food and materials contaminated byinfected rodent excrement

b) Inhalation of aerosolized virus from dead mastomysc) Ingestion of mastomys as a delicacy

Person to person transmission through contact withan infected person(Fluids, tissue, secretions and

excretions) urine, feces, saliva, vomitus, blood andsemen.


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Epid.contd

Affects people of all age groups irrespective of

their sex .

Asymptomatic in ~ 80% of infected cases, but20% come down with severe multisystem disease.

Incubation period is 6-21 days.

Cases used to be highest during the dry seasonand lowest during the wet season.

Recently: highest during the change from the dry

to the wet season.

d d


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Epidcontd

Case fatality rate increases from about 1% in sporadic

cases to about 35% -65% during outbreaks.

High rate of maternal death (29%) and foetal andneonatal loss (87%).

The illness lasts for 7 - 31 days in non-fatal cases, and7 - 26 days in fatal cases.

Fatal cases among Doctors include; Dr JM Troup (Pathologist) died in Jos (1970).

Consultant Surgeon in Adamawa state (April 2011).

Two doctors have also died in the present outbreak

d d


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Epid contd

Among the VHFs, Lassa fever affects by far the

largest number of people.

It now affects larger communities in WestAfrica, outside its already broad area of ruralendemicity.( 7 cases sin the UK since 1980)

May affect between 2 to 3 million people each

year in certain portions of the West Africanregion, causing a mortality of about 10000during the same period.


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Epidemics in Nigeria

Epidemics.

Community-based: Rat to Man.Hospital-based: Human to Human.

Lassa (Borno state)- 1969.Jos (Plateau state)- 1970, 1993.

Onitsha (Anambra state)- 1974.

Vom (Plateau state)- 1975, 1977.Zankwa (Kaduna state)- 1975.

Aba (Imo state)-1989

Aboh-Mbaise (Imo state)-1989


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Epidemics contd

Lafia (Nassarawa state)-1993.

Ekpoma (Edo state)- 1989, 1993, 1999, 2005Irrua (Edo state)- 2004

Abuja (FCT)- 2009

Sporadic primary cases are probably common in somemore remote areas but underreported.


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Epidemics in other countries

Sierra Leone: Panguma, Kenema, 197183, 1997, Liberia: Zorzor, 1972; Phebe 1972, 1977, 1982;

Ganta 1977, 1982


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THE 2012 SAGA By the 5th week of the year 2012, 29 suspected cases of

Lassa fever had been reported , 8 laboratoryconfirmed with 12 deaths( CFR OF 41.4%) all from 4states( Taraba, Rivers, Nasarawa and Plateau)

So far a total of 196 suspected cases of Lassa fever, 51laboratory confirmed with 29 deaths( CFR of 14.8%)have been reported.


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Reported outbreaks of Lassa fever

as at 10th

February, 2012As at 4 days ago the virus is said to have spread to 16

states across the federation- Anambra, Edo,Nassarawa, Ondo, Plateau, Rivers, Taraba, ,Yobe,Lagos, Ebonyi, Gombe,

A total of 40 deaths have been reported including 6health care workers

More recently the MOH has reported a total of 397cases with 87 confirmed positive for Lassa

In Oyo state, there have been two suspected cases,both were confirmed negative by PCR


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Map of West Africa: Outbreaks and

Serological Evidence of Human Infection.

W d C l Af i l i f ll (1951 1989) L


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West and Central Africa mean annual rainfall (19511989), Lassa

fever nosocomial outbreaks (stars) and human seroprevalence

(%).

f f h b h


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Map of West Africa showing both Community and

Nosocomial Outbreaks

f h f


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Map of Nigeria showing sites of Lassa

virus circulation.

Mastomys nata ensis
http://jcm.asm.org/cgi/content/full/49/3/1157/F2


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Mastomys nata ensis

Taxonomyunresolved; 8 distinct species arerecognized, and several coexist in Lassa feverendemic areas. Family: Muridae.

Other Names: Natal Multimammate Rat,

Common African Rat, Soft-furred or African Soft-furred Rat.

One of the commonest African rodents.

Females possess a superfluity of teats, more thanany other rodent. (Multimammate = Latin,meaning literally "many-breasted".)

M nata ensis cont


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M nata ensis.cont Occupies a wide range of habitat, absent only

from desert, semi-desert and mountains, but

most often seen in and around humanhabitation(peri-domestic rodent).

It avoids large metropolises because it cannotcompete with the Black Rat.

It has been increasing in number since1972, whenit was found to be the natural host of Lassa virus.

It is persistently carries the Lassa virus and shed

the virus in their excreta.


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MASTOMYS NATALENSIS

THE LASSA VIRUS


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THE LASSA VIRUS

A member of the arenaviridae; enveloped, round,

pleomorphic virus.A single-stranded, bisegmented RNA virus.

Consists of two (S and L) single strands of RNAenclosed within a spherical protein coat.

The S segment codes for the major structuralcomponents such as the internal proteins (NP)and the glycoproteins, while the L segment codes

for RNA polymerase and a few structural proteins. The protein coat has a number of T-shaped

glycoproteins protruding from it, composed ofGP2 which is the base and GP1 which is the T-bar.


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THE ARENAVIRIDAEArenaviruses Origin of name YearLassaJuninMachupo

GuanaritoSabiaLCMV

Town, NigeriaTown, ArgentinaRiver Bolivia

Area, VenezuelaTown, BrazilClinical disease

196919571962

198919901933


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Physicochemical properties The virus is inactivated by:

Low level disinfectants such as QAC, Phenols, chlorinebased products and iodophor formulations( 37minutes at 60C

3% Acetic acid for 15 minutes

Ultaviolet radiation ( 1200-2000 W/CM2) for 20

minutes Heating up to 560c

Exposure to a PH of < 5.5 or . 8.5

Lassa virus cont


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Lassa virus.cont

.

Lassa Virus contd


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Lassa Virus cont d

A lifelong and silent virus carried by theM.

natalensis.

Can transiently infect asymptomatically a widerange of mammals including domestic herdsand, possibly, birds.

Lassa virus is the most virulent of the arena

viruses known to cause haemorrhagic fever.

PATHOGENESIS


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PATHOGENESIS

Pathogenesis is poorly understood.

Circulatory instability

Increased vascular permeability

Diffuse haemorrhagic manifestations

Viraemia is detectable 3-4 days after inoculation

and may last 2 weeks or more.


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Pathogenesis

Virus enters thru either RS, GIT, blood or lymphatics

Lassa fever infection is initiated in the victim.

Generalised infection with haemorrhagicdissemination to multiple organs and systems via theblood stream, lymph vessels, RT and GIT

The blood vessels are always the most affected and the

virus multiplies in cells of the RES causing capillarylesions.

Infects macrophages and vascular epithelial cells


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Pathogenesis

Cell mediated immune response generated

The capillary permeability is increased, RBC andplatelet loss followed by peripheral vasoconstrictionwith the presence of DIC that leads to haemorrhagicsyndrome.

Loss of platelet function loss of aggregation,

impaired clotting haemorrhage Inhibition of neutrophil actions

IgM produced wks later. Antibodies may persist for 4 -5yrs after an infection

Pat ogenesis cont


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Pat ogenesis.cont

Summary:

Attachment to the cellular receptor for Lassavirus; -dystroglycan.

This subunit of dystroglycan is an important cellsurface receptor for proteins of the extracellular

matrix (ECM) and is crucial for normal functionand development of the organism.

Lassa virus efficiently competes with ECMproteins for receptor binding and likely affects the

function of dystroglycan in the host cell. Upon receptor binding, the virus undergoes

endocytosis and is delivered to acidifiedendosomes.

Pat ogenesis cont


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Pat ogenesis cont Generally the virus causes:

Endothelial cell damage/capillary leak

Platelet dysfunction

Suppressed cardiac function

Release of cytokines and other soluble mediators ofshock and inflammation.

Virological & immunological parameters


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Virological & immunological parameters

in a patient with fatal Lassa fever

Biochemical parameters


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Biochemical parameters



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Haematological parameters


CLINICAL FEATURES


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CLINICAL FEATURES

SYMPTOMS:

Asymptomatic-90% of cases Early, Insidious symptoms

Fever

Chills

RigorsHeadache

Malaise

Myalgia

Second week symptomsLower Abdominal Pain

Intractable Vomiting

Other symptoms: Tinnitus,Epistaxis,Bleeding gums,Maculopapular rash, Cough,Dizziness.

C inica eatures cont


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C inica eaturescont

SIGNS:

EarlyFever

Flushing of face and neck area

Pharyngitis (progressive over first week)

Raised patch of whitish exudate on tonsillar pillar

Pseudomembranes may develop

Oral Ulcerations

Generalized non-tender Lymphadenopathy

LaterFacial and neck swelling

Conjunctivitis

C inica eatures cont


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C inica eaturescont

Severe, Acute Phase

Systolic Blood Pressure below 90mmHg

Pulse Pressure less than 20

Relative Bradycardia

Onset and duration of principal signs & symptoms


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Onset and duration of principal signs & symptoms

C in Features cont


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C in Features cont LASSA FEVER IN CHILDREN AND INFANTS:

Significant cause of paediatric hospitalizations insome areas of West Africa.

Signs and symptoms most often similar to adults.

Swollen Baby syndrome:Anasarca, Abdominal

distension & Bleeding.Poor prognosis.

LASSA FEVER IN PREGNANCY:

Maternal mortality. Placental Infection.Foetal/Neonatal mortality. Level of viraemia.

Evacuation of uterus improves survival.

Clin features contd


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Clin features cont dSENSORINEURAL HEARING DEFICIT: common

Typically appears during early convalescence.

Not related to severity of acute illness.

Occurs in one-third of cases (>other viral infns).

May be bilateral or unilateral.

May persist for life in up to 1/3 of cases.

DIFFERENTIAL DIAGNOSIS:

Malaria Bacterial meningitis

Typhoid fever Arboviral infection

Strep Pharyngitis Leptospirosis

Bacterial sepsis Anicteric hepatitis

Bacterial or Viral conjunctivitis


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COMPLICATIONS Mucosal bleeding (17%),

Sensorineural hearing deficit (4%),

Pleural effusion (3%), and

Pericardial effusion (2%).

Alopecia

Loss of coordination

Psychiatric disorders

Sleep disorders

PATHOLOGICAL FEATURES


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PATHOLOGICAL FEATURESDescriptions of pathological findings are

limited Liver and Spleen has most striking

histopathological changes.

Gross FindingsConstant but non specific findings include:Congestion of the visceraOedema of the soft tissue

Petechiae (especially of the GIT)Pleural effusion and ascitisLuminal intestinal bleedingCongestion of meningeal blood vessels

Oedema of the vocal cords

Pathological features contd


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Pathological featurescont d

HISTOPATHOLOGICAL FINDINGS

Liver: Has most distinctive features and ishistologically the main target organ.

Necrosis of individual hepatocytes and foci ofhepatocellular destruction with multiple porto-portal and porto-central necrotic Bridges.

Eosinophilic cytoplasmic inclusions withpyknosis of the nucleus. Councilman-like bodies

with prominent nucleoli.

Path findingscontd


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g

Heart: Congestion, Slight interstitial oedema andnon specific pericardial infiltrates.

Lungs: Congestion and oedema, interstitialpneumonitis with mononuclear cells infiltration.

Kidneys: Occasional focal tubular and glomerular

necrosis.Spleen: Congestionand atrophy of the white pulp

with deposition of amorphous eosinophiliccellular debris and fibrin in the white pulp andinfiltration of the intima of splenic veins bylymphoid cells.

Laboratory Diagnosis


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Laboratory DiagnosisNine specialist centers have been opened across the

country where diagnosis of Lassa fever can be

made.

The first of such is the Lassa Fever DiagnosticLaboratoryCommissioned at Irrua (Edo state) in2008. It has ultramodern diagnostic equipmentdonated and installed by the Harvard University,Boston, USA and Benerd-Nocht Institute ofTropical Medicine, Hamburg, Germany.

Lassa Fever Isolation Ward also underconstruction in the same centre.

DIAGNOSIS


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DIAGNOSIS

Early diagnosis is still difficult in almost all

Nigerian health care institutions. Clinical diagnosis often difficult.


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LABORATORY DIAGNOSISSpecimens include; Blood, urine, pleural fluid, throatswab

In case of death, pathological materials from liver,kidney, spleen and heart

Lab diagnosis of Lassa fever is best done in a BiosafetyLevel 4 laboratory where there are adequate facilitiesfor ensuring safety such as;


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Lab Diagnosis Microscopy

Electron microscopy

Culture

Intracerebral infection of Albino mice or guinea pigs

First 7 to 10 days positive cell cultures (Vero cells)

Serology Sero diagnosis IgM antibody detection either by

ELISA or IFA , CF, RIBA

ELISA Can diagnose past infections


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PRP Molecular method

RT-PCR- Useful for detecting glycoprotein precursorprotein

Useful for confirmation of cases

Supportive tests

Liver function tests- ALT & AST 10x normal, raised LDH

Urinalysis proteinuria (may be massive)

FBC lymphocytopenia, thrombocytopenia

Chest x-rays, obtained if lung involvement is suspected,may show basilar pneumonitis and pleural effusions.

TREATMENT


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TREATMENT Key to effective treatment is early diagnosis

within 6 days of infection

Ribavirin (guanosine analogue)

Most effective when started within the first six

days of illness.Best given intravenously (IV)

Major toxicity: Mild haemolysis and suppressionof erythropoiesis. Both reversible.

NB: Presently contraindicated in pregnancy butmay be warranted if mothers life is at risk.

Does not appear to reduce incidence and severity

of deafness.

Diagnostics contd


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Diagnostics cont dNine specialist centers have been opened across the

country where diagnosis of Lassa fever can be

made.The first of such is the Lassa Fever Diagnostic

LaboratoryCommissioned at Irrua (Edo state) in2008. It has ultramodern diagnostic equipmentdonated and installed by the Harvard University,Boston, USA and Benerd-Nocht Institute ofTropical Medicine, Hamburg, Germany.

Lassa Fever Isolation Ward also underconstruction in the same centre.

Treatment contd


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Treatment cont d

Dosage:

Load: 2 grams

First Maintenance: 1 gram every 6 hours for 4days

Next Maintenance: 0.5 grams every 8 hours for6 days

NB: Post-exposure prophylaxis is now

practiced empirically using oral ribavirin, butits usefulness has not been systematicallystudied.


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Treatment ctd Supportive measures include; Fluid and electrolyte

balance, hemodynamic measures, ventilation anddialysis support. Treatment of superimposed bacterial

infection. The following drugs are contraindicated in patients

with Lassa fever;

Anticoagulants

Acetylsalicylate

NSAIDS

Clin.. Features contd


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Clin.. Features cont d

INDICATORS OF POOR PROGNOSIS:

High viraemiaSerum AST level >150IU/L

Bleeding

Encephalitis

Oedema

Third trimester of pregnancy

PREVENTION AND CONTROL


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PREVENTION AND CONTROLVillage-based programmes for rodent control and

avoidance.Awareness campaigns to farmers who live on the

hinterland to discourage drying their grains onroad shoulders along the highway

All rodent holes should be blocked and rat trapsshould be used for trapping and killing rodents

Food should be stored in rodent proof

containers Rodents should be avoided as food source


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PREVENTION AND CONTROL Hospital training programmes to avoid nosocomial spread:Barrier nursing and use of PPE

The Federal Government has inaugrated a 23-man Lassa

fever Rapid Response Committee to investigae, prevent andcontrol further spread of the disease

More Lassa fever testing centre have been established

Specific antiviral chemotherapy (Ribavirin) should bereadily available and accessible at no cost to the patient

However, there is need for more concerted effort to wardsproducing an effective vaccine for prevention andtreatment of disease


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HOSPITAL BASED CONTROL

PROGRMAMMESA patient with VHF can come to the hospital at any

point in his or her illness, including during the IPwhen the possibility of exposure is often highest.

Because a health worker cannot always know when apatient's body fluids are infectious, StandardPrecaution should be used with all patients in thehealth care setting, regardless of their infection status.

Standard Precautions are designed to preventunprotected contact between the health care workerand


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PROGRAMME Standard Precautions are designed to prevent

unprotected contact between the health care workerand blood and all body fluids whether or not they

contain blood.When a specific diagnosis is made, additional

precautions are taken, based on how the disease istransmitted.


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PROGRAMMEHealth facilities should establish and maintain a basic,practical level of Standard Precautions that can be used .

All Hospitals must have baseline protocool /guideline forensuring safety of health workers from highly infectiousdisease agents.

The following must be established- A source of clean water- Routine handwashing before and after

contact with a patient who has fever- Safe handling and disposal of sharp instruments

and equipment, including needles and syringes.- VHF Isolation facilities


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PROGRAMME Isolate the patient in rooms with negative pressure

ventilation.

Wear protective clothing in the isolation area, in the

cleaning and laundry areas and in the laboratory. ThePPE includes; a scrub suit, gown, apron, two pairs ofgloves, mask, hood, eyewear, and rubber boots.

All spills and waste must be disinfected before

cleaning and reusable equipment must be properlydisinfected.

All soiled linens must be disinfected and safe laundryshould be ensured.


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PREVENTION AND CONTROL Use safe disposal methods for non-reusable supplies

and infectious waste.

Provide information about the risk of VHF

transmission to health facility staff.

Reinforce use of VHF Isolation Precautions with allhealth facility staff.

Provide information to families and the communityabout prevention of VHFs and care of patients.


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PPE


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LASSA FEVER VACCINE


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Research is still underway to develop an effective

vaccine for Lassa fever. Preferably a live vaccine which may be given as a

single shot.

A killed vaccine is more stable, but usuallyrequires repeated shots.

Live vaccine could be combined with a yellowfever vaccine, using the same cold chains.

None of the vaccines underway have reachedclinical trial.

Programmatic use of a vaccine in endemic areas

could reduce the incidence of Lassa fever.

LASSA VIRUS AN AGENT OF BIOTERRORISM


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Bioterrorism has brought new resources to Lassa

virus science. Research on the use of Lassa virus as a weapon of

bioterrorism as been concluded

This is because the virus can be disseminated viaaerosolization, it has a low infectious dose, it isassociated with high morbidity and mortality andit also causes fear and panic in the public.

All these has helped to draw a lot of publicattention to Lassa fever


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SO MANY QUESTIONS???

Who would have related his job to his illness?

Who would remember that he said he saw ratdroppings in the store room?

How many of this modern super stores are free fromrats

How many times have we bought canned drinks,

refused to wash , but opened them and drank directlyfrom the can?

How sure are we that those cans are not encrusted withdried rat urine ?

FINALLY


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FINALLY

Lassa remains a disease of great public health

significance . It is endemic in West Africa,particularly Nigeria. The pathogenesis is stilllargely poorly understood but it affects almostevery organ of the body

Clinical diagnosis is often difficult whileLaboratory diagnosis not always available.Ribavirin is effective if given early but for now

there are no vaccines available Hence good Infection control practice remains

the mainstay of prevention for now.

REFERENCES:


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1- Ehichioya DE et al: Current molecular epidemiology ofLassa virus in Nigeria. J Clin Microbiol; 2011; 49:1157-61

2- Ehichioya DE et al (2010); Lassa fever Nigeria 2005-2008:CDC Letter volume16 Number 6.

3- Scott M (2011); Lassa fever: Family practice notebook LLC.

4-Inegbenebor U et al (2010); Prevention of lassa fever in

Nigeria: Transaction of the royal society of tropicalmedicine and hygiene.

5- Gnther S & Lenz O (2009); Lassa virus: Crit Rev Clin LabSci.

6- Senior K (2009); Lassa fever: current and future controloptions, The Lancet.

References contd7 Adewuyi GM Fowotade A & Adewuyi BT (2009); Lassa


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7- Adewuyi GM, Fowotade A, & Adewuyi BT (2009); Lassafever: Another infectious menace, Afr Jnl Cli ExpMicrobiology.

8- Premium papers on Lassa fever (2011); History, pathology,and effects on the indigenous populations:essaysample,com

9- Idemyor V (2010); Lassa virus infection in Nigeria:

Clinical perspective overview, J Natl Med Assoc.10- Ogbu O, Ajuluchukwu E, & Uneke CJ (2007); Lassa fever

in West African Sub region: An Overview, J vector BorneDis.

11- CDC Lassa Fever Fact Sheet.12- Elisabeth F & David JR (2009); Risk maps of lassa fever in

West Africa: Neglected Tropical Diseases.

13- Russel Tofts (2009); Multimammate Mice:

http://homepage,ntlworld.com/jean.wright93/mm.htm

References contd


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14- Susan PF et al (2004); Lassa fever vaccine: Expert reviewof vaccines.

15- Tribune newspaper 6th April 2011.

17- Vanguard newspaper 2nd March 2011.

18- Cummins et al (1990); Acute sensorineural deafness inlassa fever: J Amer Med Assoc.

19- Fisher-Hoch SP et al (1995); Review of cases of

nosocomial Lassa fever in Nigeria: the high price of poormedical practice, BMJ.

20- Jinn WC Jr & Walker DH (1975); The pathology ofhuman lassa fever: Bulletin WHO Vol 52.

21- Fisher-Hoch SP (2005); Lessons from nosocomial viralhaemorrhagic fever outbreaks: Br Med Bull

22- Emilie Lecomte et al (2006); Mastomys natalensis andlassa fever, West Africa: Emerging infectious diseases.

References contd


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23- Bannister B (1991); Lassa fever: BMJ.

24- Peters CU et al (1989); Pathogenesis of viral

haemorrhagic fevers: Rift valley fever and Lassa fevercontrasted, Reviews of infectious diseases.

25- Wikipedia, The free encyclopedia: Natal MultimammateMouse (updated sept, 2011)

26- Edington GM & White HA (1972); The pathology ofLassa fever: A tribute to the late Dr JM Troup, Trans ofRoyal Soc Trop Med & Hygiene.

27- Maria SS & Igor SL (2009); Vaccines against Lassa fever,

Levine Ch 82, Informa Publishing, USA.


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