ABDULRAHMAN MOHAMMEDL-2012-V-21-D

SCHOOL OF PUBLIC HEALTH AND ZOONOSES, GADVASU

INTRODUCTION• Acute 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

Also endemic in countries of the Manu river basin in West Africa- Sierra Leone, Guinea and Liberia.

Zoonosis, with reservoir in the multimammate rat Mastomys natalensis.

Naturally causes disease only in humans.

HISTORY AND CASE STUDIES19th January 1969 Laura Wine, 65 year old femaleAmerican missionary nurseDescribed as very hardworking and hardly taking a

holidaybecame acutely ill, she had been in Lassa for four

years Had fever, back pain, sore throat

LAURA WINE• Dr Hamer the only doctor at the

station became worried over her deteriorating condition

• She had – petechiae haemorrhage, – anuria. – Cloroquine, procaine penicillin – but no improvement – She started convulsing,

• Flown to Evangel hospital formerly Bingham Memorial hospital in Jos.

Laura wine

Evangel Hospital Jos• Dr Jeanette Troup continued treatment• But Laura Wine

– had internal haemorrhage, – went into shock – and DIED.

• Charlotte Shaw – nurse at the Evangel Hospital in Jos – Described as kind, loving and generous. – nursed Laura Wine intimately

Charlotte Shaw

• On the day before Laura Wine died,

– Charlotte Shaw had given her oral toileting

– cleaning her mouth with gauze wrapped round her index finger.

– She had earlier that morning pricked her finger while plucking flowers for another patient.

• Soon after Laura Wine died, Charlotte Shaw became ill.

• Dr. Jeanette Troup, the female doctor again began to treat Charlotte Shaw. – Her note describes an illness similar to the

one that killed Laura Wine. • 11 days after she became ill, Charlotte

Shaw died.

Charlotte Shaw

CHARLOTTE SHAW

• Dr. Jeanette Troupe– Worried and confused by the death of Laura Wine and

Charlotte Shaw– decided to do an autopsy on Shaw.

• She was assisted by the head nurse Penny Pinneo. • A week later Penny Pinneo became ill. • Realizing this illness does not respond to Chloroquine and

Penicillin injections • Penny Pinneo was flown to New York.

• Dr. Jeanette Troup herself later developed similar illness and died

Penny Pinneo arrived New York alive. Her specimens were sent to the Yale Arbovirus

research laboratory.

In Yale, a new virus was isolated by a team of scientists led by Jordi Casals after a couple of them got infected and one died.

Penny Pinneo survived and returned to Nigeria to continue her missionary work.

The virus that was isolated was named Lassa Virus.This was the pattern for all haemorrhagic fevers. They were

named after the town where the index case got infected. In this case in Lassa town, in the Yedseram river valley in

the southern part of Lake Chad, Borno State, North Eastern Nigeria.

In this way, Lassa virus first announced itself, by claiming a team of missionary health workers.

That has continued to be the pattern of epidemic outburst.Between 1969 and 1987, 17 reported outbreaks (11 hopspital-

44% fatality-,2 lab, 2 community), 386 patients, 27% morality

Lassa Fever has been known to erase families, teams of health workers and communities

The Ihumudumu epidemic was equally dramatic. In 1984 in Ihumudumu Community of Ekpoma, Edo

state, a woman had just died

while her burial arrangements were being made, her husband also died of a similar febrile illness.

They had 2 sons One was a Medical doctor in Ekpoma The second was a Chicago-based Engineer. They had all attended the burial. • Shortly after, the medical doctor in Ekpoma became ill.• with fever, sore throat and proteinuria, • a couple of days later he was bleeding from all orifices

including injection sites • His colleagues desperately tried to save him• A few days after burying his parents, he died

LASSA VIRUS: GENUS:ARENAVIRUSFAMILY: ARENAVIRIDADE• 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:

– heating to 56o C – pH<5.5 or >8.5– UV/gamma irradiation– detergents

LASSA FEVER VIRUS

LASSA VIRUS

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

Rodent ReservoirMastomys species complexTaxonomy still unclear

M. huberti: more common in peridomestic habitatM. erytholeucus: more common in brush habitatOthers

Known Distribution of Mastomys

LASSA FEVER IN AFRICA

The dissemination of the infection can be assessed by prevalence of antibodies to the virus in populations:

Sierra Leone 8-52%,

Guinea 4-55%

Nigeria 21%.

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

TransmissionHuman-to-human:

Direct contact with blood, tissues, secretions or excretions of infected humans

Needle stick or cut

Inhalation of aerosolized virus

PathogenesisEndothelial cell damage/capillary leak

Platelet dysfunction

Suppressed cardiac function

Cytokines and other soluble mediators of shock and inflammation

Clinical courseOnce the virus enters human body, it is

asymptomatic in 80% It is only in 20% that it takes a complicated course of

varied symptoms incubation period of 1-3 weeks, thereafter, illness last for another 3-weeks resulting in

death or recovery

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% but only 1% of

overall cases• Particularly severe in pregnant women and their offspring• Deafness a common sequela

Clinical Signs and Symptoms

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 FeverTypically 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

Lassa Fever in Animals• Natural infection in M. natalensis• Persistent infection with viremia and viruria• Carrier females give birth and offspring infected

within 2 weeks• No clinical signs observed• Carriers smaller, weighed less and had more frequent

inflammatory lesions than non-carriers -follicular hyperplasia of the skin, myocarditis, myocitis

Definition for a Suspected Case of LassaFever > 38oC for LESS than 3 weeks AND

ABSENCE of a clinical response after 72 hours of anti-malarial treatment and/or a broad-spectrum antibiotic AND

2 major signs OR1 major sign AND 2 minor signs

Major and minor signs for surveillance

Major SignsAbnormal bleeding (from the mouth, nose, rectum, and/or vagina)Edema of the neck and/or faceConjunctival or sub-conjunctival haemorrhageJaundiceSpontaneous abortionBuzzing in the ears or acute deafnessPersistent hypotensionConfirmed contact with a patient suffering from Lassa feverElevated liver transaminases (SGOT/AST

Minor SignsGeneral malaiseHeadacheRetrosternal painMuscle or joint painVomitingCoughSore throatAbdominal painDiarrhoeaProteinuriaLeucopenia < 4000/μL

Differential Diagnosis of Lassa Fever• Malaria• Typhoid fever• Streptococcal pharyngitis• Leptospirosis• Bacterial sepsis• Bacterial meningitis• Arboviral infection• Anicteric hepatitis• Enterovirus infection• Bacterial or viral conjuctivitis

DiagnosticsClinical diagnosis often difficultELISA (Enzyme-linked immunosorbent assays) for

antigen, IgM, and IgGAs research tools:

Virus isolationImmunohistochemistry (for post-mortem diagnosis)RT-PCR (Reverse transcription-polymerase chain

reaction)

Treatment• Supportive measures (monitor fluid, electrolyte

and oxygen levels)• Ribavirin(60mg/kg/day for 4 days IV, then

orally 30mg/kg/day orally thereafter)– 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

Associated with Poor Prognosis in Lassa Fever if…High viremia ≥ 10(3.6) TCID50 per milliliter on

admission associated with a case-fatality rate of 76% Serum AST level >150 IU/L at admission associated

with 55% mortality rateIntravenous ribavirin within first 6-7 days of fever

associated with reduced mortality (5-9% vs 55-76%)BleedingEncephalitisEdemaThird trimester of pregnancy

Prevention and ControlVillage-based programs for rodent control and

avoidanceSafe food storageWet down surfaces before sweeping

Hospital training programs to avoid nosocomial spread: barrier nursing manual

Diagnostic technology transfer

Specific antiviral chemotherapy (ribavirin)Research is currently underway to develop a vaccine

Rodent ControlProper 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 sourceAvoid bush burning

Lassa fever in Nigeria

Lassa Fever in Nigeria as at 27 September 2013 • Disease has spread from six states of the country in 2009 to 23 in 2013.

Institute of Lassa Fever Research and Control at the Irrua Specialist Teaching Hospital, Irrua, Edo the 2013 World Lassa Fever Day.

• At least 93 persons have died from complications associated with Lassa fever between January, 2011 and September, 2013 even as 377 patients that were diagnosed with the disease were admitted within the period under review.

• Of the number of deaths recorded, 17 people have so far died in 2013• Decline in the number of deaths attributed to the awareness that is being

created by the institute.

• Through the activities of the Institute of Lassa Fever Research and Control at the ISTH, the case of fatality from Lassa at the hospital, has dropped from between 60 to 80 per cent in the start of the new millennium to between 30 to 45 per cent.

• Millions of Nigerians are unaware of the dangers posed by Lassa fever and as a result are not taking preventive measures to avoid the disease.

• before vaccination is available, access to the right information about Lassa fever would drastically reduce its incidence.

LASSA FEVER: RE-EMERGING?

Morens et al 2004

Emerging infectious diseases are diseases that (1) have not occurred in humans before (this type of emergence is difficult to establish and is probably rare); (2) have occurred previously but affected only small numbers of people in isolated places (AIDS and Ebola hemorrhagic fever are examples); or (3) have occurred throughout human history but have only recently been recognized as distinct diseases due to an infectious agent (Lyme disease and gastric ulcers are examples)Re-emerging infectious diseases are diseases that once were major health problems globally or in a particular country, and then declined dramatically, but are again becoming health problems for a significant proportion of the population (malaria and tuberculosis are examples)NIH (US)

Factors Responsible For Emergence and Re-Emergence of Diseases Human demographic factorsHuman behaviourDeforestationBush burningInternational travel and commerceLand useHealth infrastructure

REFERENCES WHO websiteCDC websitePANO (2006). Richmond and Baglore (2003)Morens et al. (2004)Becker and Barry (2009)Adewuyi et al. (2009)Palmer et al. (2011)Punch newspaper (September27, 2013)

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