Approach
There is no specific approved antiviral treatment for VEEV infection. Some patients with VEEV infection are asymptomatic and do not require treatment. Most cases of VEEV infection result in symptoms that resemble influenza or dengue fever (e.g., acute onset fever, headache, malaise) that are mild in severity and self-limiting, and require only supportive care. If neurological symptoms develop, however, hospitalisation with administration of anticonvulsants and airway protection may be necessary. In the event of haemorrhage, transfusion of blood products may be required.
Supportive care for symptomatic patients
Supportive care for mild infection includes ample oral fluid intake (i.e., enough fluids to be passing clear urine) and use of analgesics and/or antipyretics (e.g., paracetamol).
Vomiting occurs in around 55% to 60% of patients with VEEV infection, and diarrhoea occurs in around 23% of patients.[4][5][27] If there is severe dehydration due to vomiting and diarrhoea, the patient is hospitalised, if possible, and treated with oral or intravenous fluids, along with an anti-emetic agent (e.g., ondansetron). Initial administration of a single oral dose of ondansetron may obviate the need for intravenous fluids or hospitalisation in children.[41] Other anti-emetics are not recommended due to lack of benefit and risk of adverse effects.
Pregnant women with symptomatic VEEV infection are monitored carefully, because of reports of stillbirth and spontaneous abortion associated with maternal infection.[32]
Management of neurological symptoms
Neurological complications resulting from encephalitis (e.g., disorientation, ataxia, and seizures) are seen in up to 14% of patients with VEEV infection, with the highest prevalence in children.[30] Patients with neurological involvement are admitted to hospital, if possible, and evaluated for seizures. Anticonvulsants are administered if there is seizure activity or a history of seizures. Benzodiazepines are preferred for the initial management of seizures, with lorazepam being most effective due to its long half-life. Phenytoin is recommended if a second drug is needed to terminate seizures. In pregnant women, phenytoin is only used in life-threatening infection, because it is potentially teratogenic. If a patient is taking certain anticonvulsants, serum drug levels are monitored to ensure that therapeutic levels are achieved. The airway is secured by intubation if the patient has altered mental status (e.g., obtundation), and mechanical ventilation is initiated.
A cranial nerve examination, fundoscopic examination, and head CT or brain MRI is performed to evaluate for cerebral oedema and elevated intracranial pressure. If intracranial pressure is elevated, head elevation, hyperventilation, and intravenous mannitol may be considered to reduce pressure.[42]
Treatment with intravenous aciclovir, to cover for possible herpes simplex virus infection, is recommended in patients with cerebrospinal fluid or imaging findings suggesting viral encephalitis; or if these results will not be available within 6 hours; or if the patient is deteriorating.[39] Empirical antibiotic therapy should also be started until bacterial encephalitis has been ruled out.[38]
Treatment of haemorrhage
If a patient has a history of haemorrhage, the severity of the bleeding is assessed and the source investigated. Nasogastric aspiration may help to identify the source of the bleeding (to differentiate upper versus lower gastrointestinal [GI] bleeding). It is unclear whether bleeding may be stopped by endoscopic or surgical methods, but GI and surgical consultations are warranted.
Serial haemoglobin (Hb) measurements are performed. If Hb is <7 g/dL (<4.3 mmol/L), blood transfusions and fluid resuscitation are usually initiated. Once typed and cross-matched, blood transfusions are administered with the goal of maintaining Hb ≥7g/dL (≥4.3 mmol/L). Intravenous access is established with bilateral, peripheral, large bore (16 g) lines, and fluid resuscitation commenced with crystalloids or colloids (administer 3 mL for every 1 mL lost).
If bleeding is brisk and the patient is hypovolemic, blood transfusions can be considered even if Hb is normal (i.e., 13.5 to 17.5 g/dL for men; 12.0 to 15.5 g/dL for women). For patients with comorbidities that put them at risk of fluid overload (e.g., heart failure), monitoring by pulmonary artery catheter may be necessary.
The pathogenesis of GI bleeding as a result of VEEV infection is not fully understood, but histopathological studies demonstrate massive depletion of lymphocytes due to lymphoid follicle necrosis of the GI tract, suggesting that GI bleeding may be a consequence of tissue breakdown and inflammation in the GI tract.[35]
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