Lassa fever overview

# Overview
Lassa fever is an acute viral hemorrhagic fever caused by Lassa virus, a zoonotic, single-stranded RNA virus that is transmitted to humans by the Mastomys natalensis rodent. Lassa fever is endemic to West Africa with an annual incidence of 300,000 to 500,000 cases and a case fatality rate of approximately 5%-15%. Risk factors in the development of Lassa fever include travel to endemic regions (West Africa), exposure to infected individuals or rodents, and occupational exposure in healthcare settings. Pregnant women, immunosuppressed patients, and young patients are at high risk of developing Lassa fever-associated complications. Following exposure, infected patients remain asymptomatic for approximately 3 to 21 days. The majority of patients experience no or mild clinical manifestations. Typically, patients first develop persistent high-grade fever and other non-specific signs and symptoms. If left untreated, the majority of cases self-resolve. However, clinical manifestations may progress, and patients may experience hemorrhage, deafness, edema, seizures, coma, and death. Lassa fever is usually diagnosed by detection of Lassa antibodies in the patient's serum using ELISA. The mainstay of therapy of Lassa fever is antiviral therapy with ribavirin. Ribavirin has been demonstrated to be most effective when administered intravenously early in the course of the disease (optimal efficacy when administered early within the first 6 days of symptom-onset). In addition to antiviral therapy, patients should receive supportive care to adequately maintain respiratory status and fluid and electrolyte balance. While there is no vaccine against Lassa fever, avoiding infected individuals or rodents and proper handling of infected waste products are recommended for the primary prevention of Lassa fever.

# Historical Perspective
The first case of documented Lassa fever was reported in 1969 following the death of 2 nurses in Lassa, Nigeria.

# Pathophysiology
Lassa fever may be transmitted from either infected animals (typically rodents) or humans following exposure to body fluids and excretions/secretions from the respiratory tract or GI tract. Following transmission, Lassa virus infects the endothelium and replicates intracellularly using an L-polymerase enzyme and nucleocapsid protein NP, which synthesize ribonucleoprotein (RNP) that produces mRNA and antigenomic RNA required for transcription. NP protein helps the virus evade the host immune system. Following transcription, vascular dysfunction ensues, resulting in the development of clinical manifestations of the disease. Although all organs may potentially be infected, the liver is a common target organ, and hepatitis/hepatic necrosis is typical following Lassa fever infection.

# Causes
Lassa fever is caused by the Lassa virus, a member of the zoonotic Arenaviridae family. It is an enveloped, single-stranded, bisegmented RNA virus. The natural reservoir of Lassa virus is the Mastomys natalensis rodent (multimammate rat/mouse) that sheds the virus in urine and fecal droppings.

# Differentiating Lassa fever from other Diseases
Lassa fever must be differentiated from other diseases that cause hemorrhagic fever, diarrhea, muscle fatigue, such as Ebola infection, Typhoid fever, Malaria, Diphtheria, Legionellosis, Congo-hemorrhagic fever, yellow fever, and Shigellosis.

# Epidemiology and Demographics
Lassa fever is endemic in West Africa and is rare in developed countries. The annual incidence of Lassa virus is 100,000-300,000 individuals with a case fatality rate typically reaching 1-5% but may be as high as 65% during outbreaks. There is no predilection to specific age groups, gender, or race. However, young age and pregnancy are associated with increased risk of Lassa fever-associated

# Risk Factors
Risk factors for Lassa fever include travel to endemic regions (West Africa), exposure to infected individuals or rodents, and occupational exposure in healthcare settings. Pregnant women, immunosuppressed patients, and young patients are at high risk of developing Lassa fever-associated complications.

# Natural History, Complications and Prognosis
Following exposure, infected patients remain asymptomatic for approximately 3 to 21 days. The majority of patients experience no or mild clinical manifestations. Typically, patients first develop persistent high-grade fever and other non-specific signs and symptoms. If left untreated, the majority of cases self-resolve without intervention. However, in the minority of cases, clinical manifestations may progress to hemorrhage, deafness, abdominal/chest pain, pleural/pericardial effusions and ascites, and facial edema. Eventually, manifestations progress to include convulsions, hypovolemic shock, coma, and eventually death. The most common complications of Lassa fever are neurosensory deafness and hepatic injury, which may be a mild hepatitis or fulminant hepatic necrosis. Although prognosis of Lassa fever is generally good but development of complications, pregnancy, infancy, and immunosuppression are associated with poorer prognosis and increased risk of death.

# Diagnosis

## History and Symptoms
Common symptoms of Lassa fever typically include persistent, high-grade fever and other non-specific symptoms, such as headache, myalgia/arthralgia, cough, conjunctival injection, and vomiting. Less commonly, patients may present with more severe symptoms, such as GI bleeding, deafness, confusion, seizures, and coma.

## Physical Examination
Persistent, high-grade fever is the most common sign on physical examination. Other common signs on physical examination include tachycardia, tachypnea, conjunctival injection, abdominal/chest tenderness, pharyngitis with tonsillar exudates, and hepatosplenomegaly.

## Laboratory Findings
Acute Lassa fever is usually diagnosed by detection of IgG Lassa antibodies in the patient's serum using ELISA. Additional investigations are also required following diagnosis to monitor the course of the disease for development of complications and target organ damage.

## Other Diagnostic Studies
Other diagnostic tests to confirm the diagnosis of lassa fever include reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry using either skin, tissue or liver tissue.

# Treatment

## Medical Therapy
Management of Lassa fever includes supportive care and administration of intravenous (IV) ribavirin. Data on the efficacy of antiviral agents in Lassa fever are scarce. IV ribavirin was previously evaluated for treatment of Lassa fever and demonstrated a reduction in mortality when administered anytime during the course of the disease, especially early within the first 6 days of symptom-onset. Ribavirin is administered intravenously for a total of 10 days using the following regimen: first, loading dose of 30 mg/kg (max. 2g) followed by a dose of 16 mg/kg (max. 1g) IV q6h for 4 days, followed by a dose of 8 mg/kg (max. 500mg) IV q8h for 6 days. In addition to antiviral therapy, management includes supportive care to adequately maintain respiratory status, as well as fluid and electrolyte balance.

## Primary Prevention
There is no vaccine for Lassa fever. Primary transmission of the Lassa virus can be prevented by avoiding contact with Mastomys rodents, especially in the geographic regions where outbreaks occur. When caring for patients with Lassa fever, further transmission of the disease through person-to-person contact or via nosocomial routes can be avoided by taking preventive precautions against contact with patient secretions.