Lassa Fever

1. LASSA FEVER

2. INTRODUCTION
 Lassa fever is a hemorrhagic illness caused
by Lassa virus.
 Lassa fever was first recognized in Lassa,
Nigeria, in 1969 and is endemic to West
Africa; there are approximately 300,000
cases and 5000 deaths annually.
 Lassa virus is a single-stranded RNA virus
belonging to the Arenaviridae family and
has been classified as a category A
bioterrorism agent

3. EPIDEMIOLOGY
 Lassa fever is endemic in parts of West
Africa including Guinea, Liberia, Sierra
Leone, Nigeria, Benin, Ghana, and Mali
 The prevalence of Lassa virus infections
varies within endemic areas; the incidence
is highest in the forested regions of West
Africa where Guinea, Liberia, and Sierra
Leone share a border.
 Cases of Lassa fever occur at all times of
year; the peak incidence occurs in March,
during the transition from dry to wet
season. In addition, there is a smaller
increase in incidence in December, during
the middle of the dry season.
 Imported cases of Lassa fever have been
described among returned travelers, with
a relatively high case fatality rate (>30
percent)

4. TRANSMISSION
 The primary mode of transmission to humans is via exposure
to infected Mastomys rodents via direct contact with rodent
urine and feces, inhalation of aerosolized rodent excretions,
or consumption of infected rodents as a food source
 Mastomys rodent infestation is associated with households
built of poor-quality materials, such as crumbling mud, which
facilitates rodent burrows.
 Person-to-person transmission may occur after exposure to
Lassa virus in the blood, urine, feces, or other bodily
secretions of an infected individual.
 Risk for person-to-person transmission of Lassa virus persists
after recovery; the virus is shed in the urine for three to nine
weeks and in the semen for up to three months .
RODENT CONTACT
PERSON-TO-PERSON CONTACT

5. TRANSMISSION
Reservoir Mastomys
rats
Primary human
infections
Secondary human
infections
 The virus maintains
itself in Mastomys rat
population
 Virus is present in urine
and feces of infected
rats
80 to 90 % of humans are
infected through:
 Food or household
items contaminated
by infected rat urine
and feces.
 Direct contact while
handling Mastomys
rats (food source)
 Secondary human-to-
human transmission
occurs through direct
contact with the blood
secretions, organs or
other body fluids of
infected persons

6. PATHOGENESIS
 Transmission occurs via the nasopharyngeal mucosa, where it infects dendritic cells,
monocytes, and macrophages. Subsequently, the virus spreads to regional lymph
nodes before disseminating to virtually all tissues.
 Inflammatory cell infiltrate of infected organs tends to be minimal; necrosis can occur,
particularly in the liver and spleen. Hepatic necrosis can be significant, involving up to
40 percent of hepatocytes. Splenic necrosis, adrenocortical and pituitary necrosis,
interstitial myocarditis, alveolar edema, and renal tubular injury are also
common.Severe disease appears to result from vascular instability and impaired
hemostasis.
 Lassa virus stimulates macrophages and dendritic cells to release soluble mediators
resulting in the endothelial dysfunction, insufficient effective circulating intravascular
volume, and multiorgan failure. This results in pleural effusions and pulmonary
edema, ascites, and hemorrhagic manifestations of the gastrointestinal mucosa.
Hemorrhage has also been associated with a circulating inhibitor of platelet
aggregation and thrombocytopenia.
 Among survivors, Lassa virus levels peak between days 4 and 9 of illness, and serum
viral RNA can be detected for up to three weeks after recovery. Cell-mediated

7. CLINICAL MANIFESTATIONS
 The incubation period is 1 to 3 weeks.
 Most infected individuals (approx. 80%) have mild symptoms (low-grade fever,
malaise, and headache) and may not seek medical attention.
 Disease progresses to more serious signs and symptoms in approx. 20% of
patients; these include pharyngitis, cough, nausea, vomiting, diarrhea,
myalgias, retrosternal chest pain, back pain, and abdominal pain.
 In severe cases, facial swelling, pulmonary edema, bleeding (from the mouth,
nose, vagina, or GI tract), and hypotension may develop. Proteinuria may be
noted.
 Shock, seizures, tremor, disorientation, and coma may be seen in the later
stages.

8.  The most common complication of Lassa fever is deafness, which occurs in
up to one-third of patients and may develop in the setting of mild or severe
illness. Hearing may improve after 1 to 3 months in approximately half of
cases.
 Patients who recover generally begin to improve after 8 to 10 days of
symptom onset. Poor prognostic factors include the presence of vomiting,
sore throat, tachypnea, bleeding, and diarrhea.
 Death usually occurs within 2 weeks after onset of symptoms in fatal cases.
Approximately 1 percent of Lassa virus infections result in death; among
hospitalized patients, case-fatality rates range from 15 to 30 percent.
Mortality rates can be high (≥50 percent) in the setting of nosocomial
outbreaks.

9. SYMPTOMS
 CNS – Sensorineural deafness occurs in up to 1/3 of patients, and it becomes
permanent in approximately 18%. In severe cases of Lassa virus infection,
disorientation, ataxia, and seizures can occur in as many as one-third of
patients
 Head and neck – Cervical lymphadenopathy is a common symptom of Lassa
virus infection. Pharyngitis and bilateral conjunctivitis occur in 70 and 40% of
cases, respectively. Edema of the head and neck is a distinctive feature of
Lassa fever and is seen in approx. 30% of hospitalized cases.
 Pulmonary – A dry cough may occur. Pulmonary edema and pleural
effusions may develop late in the course of disease
 Cardiovascular – Retrosternal chest pain occurs in approximately 70% of
patients. Myocarditis has been observed in some cases of Lassa fever

10.  GI – Diarrhea and vomiting are common. In severe cases, abdominal pain is
common, likely due to fluid accumulation
 Renal – Acute renal failure occurs in 28% of cases
 Rash – A maculopapular rash may appear on the thorax, face, and upper
extremities in less than 5% of cases.
 Hemorrhage –Manifestations generally consist of blood oozing from the
mouth, nose, vagina, GI tract, and cannulation and injection sites due to
endovascular leakage as well as inhibition of platelet aggregation

12. DIAGNOSIS
 The diagnosis of Lassa fever should be suspected in individuals with
suggestive signs and symptoms in the setting of relevant epidemiologic
exposure.
 Administration of empiric treatment with ribavirin is reasonable for patients in
endemic areas with symptoms strongly suggestive of Lassa fever, prior to
diagnostic confirmation.
 The preferred test for diagnosis of Lassa fever is serum reverse-transcription
polymerase chain reaction; however, this is rarely used in regions where Lassa
fever is endemic because it requires expensive equipment and technical
expertise .
 In addition, the genetic heterogeneity within and between the lineages makes
the molecular diagnosis of Lassa virus difficult.

13.  The diagnosis of Lassa fever in some endemic regions may be established via serum
enzyme-linked immunosorbent serologic assay, which can detect immunoglobulin (Ig)M and
IgG antibodies and Lassa antigen. Antigen is typically detectable at the time of symptom
onset. However, if initial testing is negative, but a high index of suspicion for Lassa fever
remains, the test should be repeated in 24 to 48 hours.
 Serum IgM is detectable 10 to 21 days after symptom onset; serum IgG is detectable
approximately 21 days after symptom onset .
 Enzyme-linked immunosorbent serologic and antigen assays take 4 to 18 hours to perform
depending on the individual platform used.
 Lassa virus may be cultured from blood, urine, or throat washings, but these are not routine
clinical diagnostic tools. A postmortem diagnosis may be established via
immunohistochemistry performed on formalin-fixed tissue specimens.
 Diagnostic evaluation of patients with suspected Lassa fever infection should also include
diagnostic testing for malaria, blood cultures, and evaluation for other infections

14. LAB FINDINGS
 Leukopenia –Patients generally have a mild leukopenia in the early stages. Subsequently,
patients may develop a leukocytosis with neutrophilia.
 Thrombocytopenia – Mild thrombocytopenia has been observed. Patients with severe Lassa
fever have significantly decreased platelet aggregation
 Elevated transaminases and amylase – Both alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) are elevated; AST is usually significantly greater than ALT. Amylase is
frequently elevated as well.
 Renal abnormalities – Renal insufficiency has been associated with increased risk of
mortality due to Lassa fever. Proteinuria is common
 Spinal fluid findings – Lassa virus has been isolated from the spinal fluid in a small number
of cases. Spinal fluid analysis in patients with Lassa fever has demonstrated mild to
moderate pleocytosis.

15. TREATMENT
 It consists primarily of supportive care, including maintenance of oxygenation and blood
pressure. Fluid replacement is important although care must be taken to avoid volume
overload due to the risk of capillary leak and renal dysfunction. Aspirin and NSAIDs should
be avoided because these agents can adversely affect clotting.
 In addition to supportive care, it is suggested to administer ribavirin for all symptomatic
patients with a confirmed diagnosis of Lassa fever.
 Ribavirin has been reported to be most effective when given within the first six days after
onset of symptoms
 Intravenous (IV) administration is preferred because higher serum concentrations can be
achieved than with oral formulations
 Loading dose 30 mg/kg (maximum 2 g), followed by 15 mg/kg (maximum 1 g) every six
hours for four days, followed by 7.5 mg/kg (maximum 500 mg) every eight hours for six
days

16. PREVENTION
 There is no vaccine for prevention of Lassa virus infection. Preventive measures include
avoiding Mastomys rodents and minimizing risk of person-to-person transmission
 Patients with known or suspected Lassa fever should be managed in healthcare facilities
whenever possible; community-based care should be avoided to minimize the risk of person-
to-person transmission. Patients with signs and symptoms of infection should be considered
contagious, even if the clinical manifestations are mild
 Blood and body fluid specimens from patients with suspected Lassa fever infection should be
considered highly infectious and handled with extreme caution.
 The body of a deceased patient should not be returned to family members; it should be
placed in a sealed body bag and trained personnel in PPE should handle and bury the body.
 Individuals should wait at least three months following resolution of Lassa fever infection
before unprotected sex.