Lassa fever natural history, complications and prognosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]

Overview

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, development of complications, pregnancy, infancy, are associated with poorer prognosis and increased risk of death.

Natural History

Incubation Period

• Infected patients remain asymptomatic for 3 to 21 days following exposure.

Development of Clinical Manifestations

• The majority of patients experience no or mild symptoms. Only a minority (approximately 15-20%) of patients experience multiorgan dysfunction, and typically 5-15% of infected patients die of Lassa fever.
• Patients typically first develop persistent high-grade fever (39 °C to 41 °C) and other non-specific symptoms, such as muscle aches, conjunctival injection, headache, sore throat, nausea, and vomiting.
• If left untreated, the majority of patients self-resolve without any intervention.
• In a minority of cases, patients may develop worsening abdominal/chest pain, temporary/permanent deafness, facial edema, mucosal bleeding and hemorrhage, pulmonary edema, pleural/pericardial effusions or ascites, multi-organ failure, and shock.
• Prolonged and worsening symptoms are usually associated with worsening prognosis, typically resulting in convulsions, encephalitis, seizures, coma and finally death.

• The following table demonstrates the 4 clinical stages of Lassa fever (adapted from McCarthy et al. 2002 and Richmond et al. 2003)

Stage	Typical Symptoms	Days Since Symptom-onset
Stage 1	High-grade fever (39-41 °C), malaise, weakness	day-1 to day-3
Stage 2	Headache, backache, chest pain, sore throat with exudation, abdominal pain, diarrhea, nausea, vomiting, hypotension, anemia, proteinuria, conjunctivitis	day-4 to day-7
Stage 3	Mucosal bleeding, internal bleeding, facial edema, confusion, disorientation and convulsion	Beyond day-7
Stage 4	Coma, death	Beyond day-14

Complications

Complications of Lassa fever include the following:

• Sensorineural Deafness
  • The most common complication of Lassa fever is deafness (1/3 of patients)
  • Deafness may be either temporary or permanent and may either by unilateral or bilateral.
  • Deafness does not seem to be associated with the severity of disease and may develop equally among patients with mild or severe infections.
• Spontaneous abortion among pregnant women
• Hepatitis and hepatic necrosis
• Splenic necrosis
• Adrenocortical necrosis
• Pulmonary alveolar edema
• Interstitial pneumonitis
• Lymph node histiocytosis
• Mucosal (e.g. GI) bleeding
• Renal tubular injury and interstitial nephritis
• Swollen baby syndrome (edema and bleeding among fetuses)

Prognosis

• Approximately 5-15% of patients hospitalized for Lassa fever die from the illness. The following factors are associated with poorer prognosis of Lassa fever:
  • Infection during the third trimester of pregnancy or during infancy
  • Increased viremia concentration
  • Serum AST level > 150 IU/L
  • Bleeding, hypotension, and shock
  • Development of encephalitis, confusion, or coma
  • Edema (facial edema, pleural/pericardial effusion, ascites)