Evaluation of Crimean-Congo hemorrhagic fever virus in vitro inhibition by chloroquine and chlorpromazine, two FDA approved molecules.

Crimean-Congo hemorrhagic virus (CCHFV) causes hemorrhagic fever with high case mortality rates and is endemic in south-eastern Europe, Africa, and Asia. The limited catalog of specific treatment, highlight the necessity to look for additional therapeutic solutions. Previous experiments suggested that CCHFV enters the cells via a clathrin dependent pathway. Therefore, we have evaluated the potential anti-CCHFV activity of several molecules targeting this entry possibility. We identified two molecules chloroquine and chlorpromazine. Neutralization and virus yield reduction assays were tested in Vero E6 and Huh7 cells on two different CCHFV strains. Several combinations, including ribavirin, were assayed to test a potential synergistic effect. The two molecules inhibited CCHFV, and depending on the virus and the cell lines, the 50% inhibitory concentration (IC50) values for chloroquine and chlorpromazine ranged from 28 to 43 and 10.8-15.7 µM, respectively. Time-of-addition studies demonstrated that these molecules had a direct effect on CCHFV infectivity and spread. The antiviral activity of the two molecules was still effective even when added up to 6h post-infection and up to 24h. The selectivity index ranging from 3 to 35 lead us to evaluate combinations with ribavirin. Combinations of ribavirin and chloroquine or chlorpromazine were synergistic against CCHFV. Though the low chlorpromazine selectivity index suggests the need for a chemical improvement, our present study highlights chloroquine as the main drug having the potential for drug repurposing.

Genetic disposition to deafness in maternal rubella: fact or myth?

Eleven parental pairs, each having a child deaf from maternal rubella, were evaluated with a battery of specialized audiologic tests. The tests which included measurement of Békésy hearing threshold and the stapedial reflex threshold at 0.5, 1.0, and 2.0 kHz were used to test the theory that these parents have a predisposition to elevated reflex thresholds, Békésy hearing threshold dips, and a history of familial deafness. The present study failed to find any history of familial deafness or Békésy dips. Elevated reflex thresholds were noted in seven couples. This proportion was shown to be significant (p less than 0.03). The relevance of these findings in light of current clinical practice is discussed. A comparison of pure tone hearing levels of the children of parents with and without elevated reflex thresholds, failed to show a significant difference.

A neonatal hearing screening research program using brainstem electric response audiometry.

Results of brainstem electric response audiometry (BERA) for intensive care nursery graduates and babies from the general nursery are described. At-risk babies received both screening and more detailed BERA before hospital discharge. The latter test was repeated after four months. From 2,597 risk assessments, 421 were at risk and 379 have been tested. The specificity of 40 dB click screening is good, but its sensitivity is only moderate. Follow-up BERA detected 25 cases of hearing loss, 12 having moderate loss in at least one ear. Discrepancies between predischarge and follow-up tests occurred, especially for mild losses. There was substantial resolution of hearing loss, but also some emergent mild loss. These changes support BERA at about four months as the determinant of habilitation, as opposed to predischarge testing. Differences between click and frequency-specific BERA were found, suggesting that click evaluations alone are insufficient.

A review of cis-platinum ototoxicity.

A review of the ototoxic effects of cis-diamminedichloroplatinum (II) (cis-platinum) is presented. Cis-platinum impairs auditory function by preferentially destroying the outer hair cells of the organ of Corti in the basal turn of the cochlea. Hair cell loss in the vestibular labyrinth has also been observed. Auditory sequelae include tinnitus and/or hearing loss, both of which are usually reversible. The incidence of tinnitus in clinical studies is about 7%. Hearing loss is noted in about 69% of patients, usually in the 4,000-8,000 Hz range, although speech frequencies (1,000-4,000 Hz) may occasionally become involved. The hearing losses range from 15-65 dB, and only 7% of all patients complain of difficulty in understanding speech. A direct dose effect relationship does not appear to exist for either tinnitus or hearing loss. The onset of hearing loss, however, appears to be related to cumulative levels of the drug. Vestibular dysfunction has also been shown to be a side effect of therapy. Case management strategies are discussed.