Recent Progress in the Treatment of Crimean–Congo Hemorrhagic Fever and Future Perspectives

Masayuki Saijo; Shigeru Morikawa; Ichiro Kurane

Disclosures

Future Virology. 2010;5(6):801-809. 

In This Article

Therapy

General Considerations

No specific therapies have been confirmed to be efficacious in the treatment of patients with CCHF. Differential diagnosis is extremely important, and it is necessary to consider other possible causes of the symptoms. After performing a septic work-up, broad-spectrum antibiotics should be considered. Supportive therapies to improve hemostasis are required, and red blood cells, fresh–frozen plasma and/or thrombocyte solutions should be administered, if necessary.[67] Preventive measures should be installed to minimize the risk of nosocomial infections.

Supportive Therapies

Essentially, maintenance therapies, such as hydration, blood transfusion and other specific supportive therapies (i.e., the administration of diuretics and/or antibiotics – if necessary), should be initiated as soon as possible. If findings consistent with DIC are demonstrated, the treatment strategy becomes more complicated because the treatment for DIC itself carries the risk of exacerbating the tendency toward bleeding. Recently, it was reported that the administration of high doses of methylprednisolone showed promise for CCHF patients, in whom findings consistent with VAHPS were demonstrated.[51] Methylprednisolone was administered to five patients at a dose of 20–30 mg/kg/day intravenously for approximately 5 days. Although one of the five patients died due to septicemia, the prognosis was good in the other patients. Although methylprednisolone administration is still purely observational, this therapy should be one of the choices for CCHF patients with VAHPS.

Specific Therapies

Antiviral Drug: Ribavirin Ribavirin is the only antiviral drug that has been used to treat CCHF. Ribavirin inhibits the replication of CCHFV in vivo and in vitro.[68,69] Ribavirin has been administered to patients orally and intravenously[10,70–78] and, although there are a relatively large number of case reports in which ribavirin was used for the treatment of CCHF, and clinical studies in which the efficacy of ribavirin was assessed, we have not yet obtained conclusive results on its efficacy. The papers describing the efficacy of ribavirin in patients with CCHF are summarized in Table 1. Some studies demonstrated its efficacy, especially when administered in the early stage of disease onset,[71,72,77,78] although other studies did not.[70,73,76] Since there are some reports on the efficacy of ribavirin, especially when prescribed at an early phase of illness, ribavirin is considered to be one of the choices for patients with CCHF under the present circumstances. A current recommended regimen, adjusted for bodyweight, is 30 mg/kg as an initial loading dose, then 15 mg/kg every 6 h (4 × 1 g) for 4 days, and 7.5 mg/kg every 8 h (4 × 0.5 g) for 6 days.[67] Ribavirin should be one of the choices for treatment of CCHF, and should be administered as early as possible.

Hematological and neurological abnormalities are common side effects induced by ribavirin treatment. In the treatment of patients with CCHF by ribavirin, adverse events due to ribavirin treatment were described, and severe adverse events were not reported in the randomized study on the efficacy of ribavirin in the treatment of CCHF patients.[73,74,79]

Passive Antibody Transfer Since viremia is prominent in the early stage of CCHF, the transfer of antibodies to CCHFV is expected to be effective as a treatment.[67] Vassilenko et al. reported the prompt recovery of seven severely ill CCHF patients treated with the passive transfer of two different immunoglobulin preparations, CCHF bulin (for intramuscular use) and CCHF venin (for intravenous use), which were prepared from the plasma of CCHF survivor donors, boosted with one dose of CCHF vaccine.[80] It appears that this therapy, based on the intramuscular and intravenous transfer of human immunoglobulin active against CCHFV, was effective as a treatment. As the number of patients treated with this drug was too small to draw definite conclusions, the treatment of CCHF with the passive transfer of immunoglobulin remains controversial. In addition, as there are no standard therapeutics with this kind of drug to date, further study, such as a placebo-controlled trial of this therapy, is required to assess its efficacy. The passive transfer of immunoglobulin against CCHFV should be administered as early as possible, once it becomes available.

Interferon It was reported that IFN-α inhibited the growth of CCHFV in human endothelial and hepatoma cells.[81,82] It was demonstrated that the IFN-induced MxA, which is induced exclusively by α and β IFNs and belongs to the dynamin superfamily of large GTPases, is a major factor mediating the antiviral effect against CCHFV. CCHFV replication was inhibited in the cells, in which recombinant MxA was inhibited, and the inhibition was due to the interaction of MxA with the viral nucleocapsid protein. However, IFN therapy in CCHF patients have not been reported, except for in one paper.[17] In the literature, IFN therapy was terminated owing to severe side effects. IFN therapy is experimental for patients with CCHF.

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