Ottesen EA et al. (1994) J Antimicrob Chemother "Ivermectin in human medicine."

Campbell WC, Ottesen EA

[J Antimicrob Chemother, 1994]

Ivermectin is a potent macro-cyclic lactone causing paralysis in many nematodes and arthropods through an influx of chloride ions across cell membranes. It is currently the drug of choice for human onchocerciasis and shows potent microfilaricidal activity against the other major filarial parasites of human (Wuchereria bancrofti, Brugia malayi, Loa loa and Mansonella ozzardi) but not against M. perstans. Whether or not it also kills the adult-stage of these parasites is currently under study. Ivermectin also has excellent efficacy in both human strongyloidiasis and cutaneous larva migrans for which good alternative treatments have not been available; and it is as effective as currently available drugs against the intestinal nematodes Ascaris lumbricoides, Trichuris trichiura and Enterobius vermicularis; against the human hookworms it shows only partial efficacy. Preliminary studies indicate that ivermectin has the potential to become the drug of choice for ectoparasitic infestations (mites, lice) of humans as well.

Ottesen EA et al. (1992) Annu Rev Med "Tropical pulmonary eosinophilia."

Nutman TB, Ottesen EA

[Annu Rev Med, 1992]

Tropical pulmonary eosinophilia is one of the many PIE syndromes [pulmonary infiltrates with eosinophilia (of the peripheral blood)]. It is caused by immunologic hyperresponsiveness to the filarial parasites Wuchereria bancrofti or Brugia malayi. Its clinical presentation includes nocturnal cough, dyspnea, wheezing, fever, weight loss, fatigue, interstitial mottling on chest radiograph, predominantly restrictive but also obstructive lung function abnormalities, and peripheral blood eosinophilia of more than 3000 per microliter. It can be distinguished from other PIE syndromes by the patient's history of residence in the tropics, by the presence of extraordinarily high levels of both serum IgE and antifilarial antibodies, and by the dramatic clinical improvement after treatment with the antifilarial drug diethylcarbamazine. Recent studies indicate that the compromised lung diffusion capacity of patients with acute tropical pulmonary eosinophilia is a function of the degree of the eosinophilic alveolitis present and that, despite a 3-week course of diethylcarbamazine, low-grade alveolitis persists in almost half of such patients; this persistent alveolitis is likely to be the cause of the progressive interstitial fibrosis seen in many untreated or inadequately treated patients with tropical pulmonary eosinophilia.

Bucher EA et al. (1994) Seminars in Developmental Biology "Gastrulation in the nematode Caenorhabditis elegans."

Bucher EA, Seydoux GC

[Seminars in Developmental Biology, 1994]

Gastrulation in Caenorhabditis elegans has been described by following the movements of individual nuclei in living embryos by Nomarski microscopy. Gastrulation starts in the 26-cell stage when the two gut precursors, Ea and Ep, move into the blastocoele. The migration of Ea and Ep does not depend on interactions with specific neighboring cells and appears to rely on the earlier fate specification of the E lineage. In particular, the long cell cycle length of Ea and Ep appears important for gastrulation. Later in embryogenesis, the precursors to the germline, muscle and pharynx join the E descendants in the interior. As in other organisms, the movement of gastrulation permit novel cell contacts that are important for the specification of certain cell fates.

Brown KR et al. (2000) Parasitology "Ivermectin: effectiveness in lymphatic filariasis."

Ottesen EA, Brown KR, Ricci FM

[Parasitology, 2000]

This detailed review of the published studies underlying ivermectin's recent registration for use in lymphatic filariasis (LF) demonstrates the drug's single-dose efficacy (over the range of 20-400 microg/kg) in clearing microfilaraemia associated with both Wuchereria bancrofti and Brugia malayi infections of humans. While doses as low as 20 microg/kg could effect transient microfilarial (mf) clearance, higher dosages induced greater and more sustained mf reduction. The single dose of 400 microg/kg yielded maximal responses, but a number of practical considerations suggest that either 400 microg/kg or 200 microg/kg doses would be acceptable for use in LF control programmes. Associated safety assessments indicate that adverse events, which occur commonly following treatment of microfilaraemic individuals, develop not because of drug toxicity but because of host inflammatory responses to dying microfilariae killed by the ivermectin treatment. Ivermectin is, therefore, a highly effective and generally well tolerated microfilaricide that may soon become an essential component of many public health initiatives to interrupt transmission of lymphatic filarial infection in an effort to eliminate LF globally.