Argentine Hemorrhagic Fever - An Overview

What Is Argentine Hemorrhagic Fever?

• Argentine hemorrhagic fever (AHF) is a severe viral hemorrhagic fever endemic to the fertile farming plain of central Argentina, known as the humid pampas. Junin virus, which belongs to the family Arenaviridae, is the etiologic agent of Argentine hemorrhagic fever, a rodent-borne virus. The principal reservoir of this virus is Calomys musculinus (rodent species). The infection occurs through human exposure via inhalation of aerosolized body fluids or excretions of infected rodents.

• Humans generally become prone to this infection during agricultural work. Alterations of the habitat concerning agricultural methods are assumed to be the leading causes of Argentine hemorrhagic fever. These environmental mutations tend to increase the population of Calomys musculinus, the pool of argentine hemorrhagic fever.

What Are the Clinical Features of Argentine Hemorrhagic Fever?

There are three clinical phases of Argentine hemorrhagic fever. These three phases are prodromal, neurological–hemorrhagic, and recovery.

1. Prodromal Phase: This stage stays for the first week from the beginning of symptoms. The onset is insidious. That is, it spreads slowly or sometimes unnoticed, but it still causes severe harm to the patients. The following are the symptoms of this phase:

• Chills.

• Malaise (a general feeling of being ill).

• Anorexia (loss of appetite).

• Headache.

• Myalgia (pain in muscles) mainly over the lower back.

• Hyperthermia (sight increase in the body temperature, that is, 38 to 39 degrees Celsius).

• Retro-orbital pain (pain behind the eyes).

• Nausea.

• Vomiting.

• Epigastric Pain (pain that occurs in the upper abdomen).

• Photophobia (discomfort due to light in the eye).

• Dizziness.

• Constipation.

• Diarrhea.

While on physical examination, the following symptoms are noted below:

• Flushing of the face, neck, and chest area.

• Conjunctival congestion: Diffuse congestion around the eyes and watery secretions.

• Periorbital edema: Swelling around the eyes.

• Gum bleeding.

• The soft palate shows petechiae (tiny round, brownish-purple-colored spots due to bleeding under the skin) and small blisters. These petechiae are also seen in the arms, chest, and the regions around the axilla.

• Cervical lymph nodes are dilated.

• Bradycardia (abnormally slow heart rate) and orthostatic hypotension (a form of low blood pressure while standing up from sitting or lying down).

• Hepatomegaly (abnormal liver enlargement), splenomegaly (spleen enlargement), and jaundice are irregular.

The following symptoms are seen at the spike of this phase:

• Irritability, lethargy, and fine tremors of the hand and tongue.

• Moderate ataxia (poor muscle control that causes clumsy voluntary movements).

• Cutaneous hyperesthesia (excessive physical sensitivity of the skin).

• Decrease in plunging tendon reflexes and muscular tonicity (continuous and partial contraction of the muscles).

• Metrorrhagia (pain during menstrual bleeding).

• Oral candidiasis (oral thrush).

2. Neurologic - Hemorrhagic Phase: This phase starts between eight and 12 days after the initial onset of symptoms. Following are the symptoms of the neurologic-hemorrhagic stage:

• Severe hemorrhagic or neurologic indications include nose bleeding, gingival bleeding, hematomas, stroke, seizures, shock, and bacterial infections like sepsis.

• Hemorrhagic signs are hematemesis (vomiting of the blood), melena (dark stools with or without blood), hemoptysis (coughing of blood), epistaxis (nosebleed), hematomas (collection of blood outside the blood vessels), metrorrhagia (abnormal bleeding in the menstruation) and hematuria (blood in urine).

• Neurological signs are mental confusion, marked ataxia (impaired balance due to damage to the brain, nerves, or muscles), increased irritability and tremors (rhythmic shaking of any part of the body), delirium (severe disturbances in mental abilities), generalized convulsions (violent movement of the body), and coma.

• Primary bacterial infections such as pneumonia and septicemia are seen. Acute tubular necrosis can also appear. Acute renal failure is irregular.

3. Convalescence Phase: This phase lasts from one to three months. The common symptoms in this phase are asthenia (lack of energy), irritability, memory transitions, and hair loss (alopecia). Some patients also acquire late neurological syndrome (LNS). The late neurological syndrome is represented by febrile symptoms (fever), cerebellar signs, and cranial nerve palsies.

What Is the Pathogenesis of Argentine Hemorrhagic Fever?

• The inhalation of aerosols from infected rodents is the primary cause of Argentine hemorrhagic fever. Viral replication occurs in the lungs, followed by contamination of different parenchymal tissues. Many organs get affected, including vascular endothelium, myocardium, kidneys, and the central nervous system (brain and spinal cord).

• Factors such as thrombocytopenia, an abnormal platelet function generated by a plasma component, and alterations in blood coagulation with fibrinolysis activation are responsible for causing bleeding in Argentine hemorrhagic fever.

• Hemostatic abnormalities (caused by blood clotting due to an injury) lead to prolonged activated partial thromboplastin time (APTT), inadequate amount of factor VIII, increased values of factor V, von Willebrand factor, and fibrinogen, reduction in antithrombin III and plasminogen.

• Viremia (presence of viruses in the blood) is prominent in Argentine hemorrhagic fever because of the appearance of enormous amounts of endogenous interferon-α (IFN-α). The quantities of IFN-α (interferon-alpha) get reduced, and tumor necrosis factor-α (TNF-α) titers improve.

What Is the Treatment of Argentine Hemorrhagic Fever?

• Ribavirin: Ribavirin (1.β.D. ribofuranosyl.1.2.4. triazole-3-carboxamide) is an appropriate antiviral used in patients suffering from Argentine hemorrhagic fever. The clinical trials were conducted on humans suffering from Argentine hemorrhagic fever and having symptoms for more than eight days. These studies were accomplished in two stages: In the first phase, researchers introduced seven patients to Ribavirin, and in the second phase, eight patients have introduced to Ribavirin, and the other received placebo. Ribavirin is delivered intravenously as per the following plan: 34 mg/kg as a loading dose, followed by 17 mg/kg every 6 hours for four days, and by 8 mg/kg every 8 hours for the following six days.

• Other Therapeutic Approaches:

  • Immune Globulins from Human Immune Plasma: These globulins get injected intravenously.

  • Monoclonal Antibodies: These antibodies are useful for therapeutic purposes. The current treatment method is premature transfusion of immune plasma in standardized doses of equalizing antibodies.

Conclusion

Argentine hemorrhagic fever is a severe hemorrhagic fever primarily caused by a virus found in rodents, known as the Junin virus. The inhalation of aerosols from infected rodents, genetic mutations, thrombocytopenia, and various hemorrhagic and neurologic abnormalities are responsible for causing the disease. Ribavirin is the primary therapeutic drug used to treat Argentine hemorrhagic fever.