Skin snips have no role in programmatic evaluations for onchocerciasis elimination: a reply to Bottomley et al.

A critique of the recommendation that skin snips be used for post-MDA surveillance of formerly endemic onchocerciasis areas is provided. After considering several fundamental aspects of the use of this methodology within the context of prolonged mass distribution of ivermectin, we argue that skin-snipping has no value for monitoring onchocerciasis elimination programs.

Importance of ivermectin to human onchocerciasis: past, present, and the future.

Ivermectin (registered for human use as Mectizan®) was donated by Merck & Co Inc in 1987 for the treatment and control of human onchocerciasis ("river blindness"). This philanthropic gesture has had a remarkable effect in reducing the incidence and prevalence of this serious ocular and dermatological disease, while changing health system support for millions of people worldwide. Over 800 million doses have been given to more than 80 million people for onchocerciasis during the past 23 years. As a result, onchocerciasis has been significantly reduced in more than 25 countries, transmission has been interrupted in foci in at least 10 countries, and the disease is no longer seen in children in many formerly endemic foci. Recent communications have suggested that the drug's efficacy as the major therapeutic agent for these control and elimination programs may be threatened, but alternative interpretations for suboptimal response/resistance suggest otherwise. Current research needs and control methods by which the public health community in endemic countries may respond to resistance, should it occur in their area, are discussed, along with the continuing importance of this anthelmintic as the mainstay in onchocerciasis control programs.

Processing of pro-thrombostasin by a recombinant subtilisin-like proprotein convertase derived from the salivary glands of horn flies (Haematobia irritans).

Thrombostasin (TS) is a thrombin inhibitor found in the salivary glands of horn flies (Haematobia irritans). It is produced as an inactive form with a 76-amino acid propeptide in the N-terminus preceding the mature TS. A minimal recognition sequence by subtilisin-like proprotein convertases, Arg-Xaa-Xaa-Arg, is localized C-terminal to the propeptide. This study demonstrated that a gene cloned from the salivary glands of the horn fly encodes a new convertase, subsequently named horn fly proprotein convertase (HFPC), and that the recombinant HFPC expressed in insect HighFive cell culture specifically cleaves recombinant pro-thrombostasin, produced in E. coli, at the expected site. The relative cleavage efficiency of rHFPC was compared with that of recombinant human furin, a commercially available proprotein convertase. The result indicated that this newly identified proprotein convertase is of importance for the proteolytic maturation of thrombostasin, a protein secreted in horn fly saliva and used by the insect to counteract its host's haemostatic response.