The document summarizes the 1969 outbreak of Lassa fever that originated in Nigeria. It describes how the American missionary nurse Laura Wine became the first known case and infected the nurse Charlotte Shaw who cared for her. Their deaths prompted an investigation that led to the discovery of the Lassa virus. The virus is endemic in West African countries and transmitted from rodents to humans. It can also spread between humans. The document provides details on the epidemiology, clinical presentation, diagnosis and treatment of Lassa fever.

1. ABDULRAHMAN MOHAMMED
L-2012-V-21-D
SCHOOL OF PUBLIC HEALTH
AND ZOONOSES, GADVASU

2. 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

3. 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.

4. HISTORY AND CASE STUDIES
19th January 1969
Laura Wine, 65 year old female
American missionary nurse
Described as very hardworking and hardly taking a
holiday
became acutely ill, she had been in Lassa for four
years
Had fever, back pain, sore throat

5. 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

6. 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

7. 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

8. • 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

9. 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.

10. 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

11. 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.

12. 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

13. LASSA VIRUS:
GENUS:ARENAVIRUS
FAMILY: 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

14. LASSA FEVER VIRUS

15. LASSA VIRUS

17. 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

18. Rodent Reservoir
Mastomys species
complex
Taxonomy still unclear
M. huberti: more
common in peridomestic
habitat
M. erytholeucus: more
common in brush habitat
Others

19. Known Distribution of Mastomys

20. LASSA FEVER IN AFRICA

22. 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%.

23. 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

24. Transmission
Human-to-human:
Direct contact with blood, tissues,
secretions or excretions of infected
humans
Needle stick or cut
Inhalation of aerosolized virus

25. Pathogenesis
Endothelial cell damage/capillary leak
Platelet dysfunction
Suppressed cardiac function
Cytokines and other soluble mediators of shock and
inflammation

26. Clinical course
Once 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

27. 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

28. Clinical Signs and Symptoms

30. 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

31. 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

32. 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

33. 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

34. Definition for a Suspected Case of
Lassa
Fever > 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 OR
1 major sign AND 2 minor signs

35. Major and minor signs for surveillance
Major Signs
Abnormal bleeding (from the mouth,
nose, rectum, and/or vagina)
Edema of the neck and/or face
Conjunctival or sub-conjunctival
haemorrhage
Jaundice
Spontaneous abortion
Buzzing in the ears or acute deafness
Persistent hypotension
Confirmed contact with a patient
suffering from Lassa fever
Elevated liver transaminases
(SGOT/AST
Minor Signs
General malaise
Headache
Retrosternal pain
Muscle or joint pain
Vomiting
Cough
Sore throat
Abdominal pain
Diarrhoea
Proteinuria
Leucopenia < 4000/μL

36. 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

37. 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)

38. 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

39. 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 rate
Intravenous ribavirin within first 6-7 days of fever
associated with
reduced mortality (5-9% vs 55-76%)
Bleeding
Encephalitis
Edema
Third trimester of pregnancy

40. Prevention and Control
Village-based programs for rodent control and
avoidance
Safe food storage
Wet 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

42. 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
Avoid bush burning

43. Lassa fever in Nigeria

44. 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.

45. LASSA FEVER: RE-EMERGING?
Morens et al 2004

46. 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)

47. Factors Responsible For Emergence
and Re-Emergence of Diseases
Human demographic factors
Human behaviour
Deforestation
Bush burning
International travel and commerce
Land use
Health infrastructure

48. REFERENCES
WHO website
CDC website
PANO (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)

49. THANK YOU FOR
LISTENING