In vitro praziquantel test capable of detecting reduced in vivo efficacy in Schistosoma mansoni human infections.

Although great reductions in human schistosomiasis have been observed after praziquantel (PZQ) mass drug administration (MDA), some individuals remain infected after multiple treatments. Many MDA programs now require monitoring for drug efficacy as a key component. No molecular tools for PZQ resistance currently exist and investigations into the dose of PZQ required to kill 50% of adult worms in vivo (ED(50)) present ethical, logistical, and temporal restraints. We, therefore, assessed the feasibility and accuracy of a rapid, inexpensive in vitro PZQ test in the laboratory and directly in the field in Uganda under MDA in conjunction with highly detailed infection intensity, clearance, and reinfection data. This test strongly differentiated between subsequently cleared and uncleared infections as well as differences between parasite populations pre- and post-PZQ treatments, advocating its use for on-the-spot monitoring of PZQ efficacy in natural foci. After only a few treatments, uncleared parasites were identified to be phenotypically different from drug-sensitive parasites, emphasizing the urgent need for monitoring of these repeatedly PZQ-treated populations.

Impaired binaural hearing in children produced by a threshold level of middle ear disease.

Otitis media with effusion (OME), a form of middle ear disease, is the most common reason for young children both to visit their family doctor and to have surgery. Almost all children have at least a single episode of OME before their first birthday and annual incidence rates exceed 50% in each of the first five years. For most children, OME occurs infrequently, but about 10-15% of children have OME during more than half of their first six years. Middle ear effusions attenuate and delay sound, causing conductive sound distortion during the crucial years for language acquisition. The many studies of OME effects on language and other indices of development have produced mixed results. However, a consensus is emerging of mild language impairment in the preschool years, with subsequent performance, emotional, and behavioral difficulties. In addition to the peripheral hearing loss produced directly by the disease, binaural and other central auditory deficits can outlive the OME. It has been unclear which children are at risk of central impairment following OME, since the children studied have generally been recruited from otolaryngology clinics. Consequently, a detailed prospective history of the middle ear status of participants has not been available. By studying six-year-old children with a lifetime known history of OME, we show in this study that only those children with a cumulative OME experience of more than about half the time during the first five years consistently have residual impaired binaural hearing.