IL-17-mediated antifungal defense in the oral mucosa is independent of neutrophils.

Interleukin-17 (IL-17)-mediated immunity has emerged as a crucial host defense mechanism against Candida albicans infections in mucosal tissues and the skin. The precise mechanism by which the IL-17 pathway prevents fungal outgrowth has not been clarified. Neutrophils are critical for limiting fungal dissemination and IL-17 is generally thought to act by regulating neutrophil mobilization and trafficking to the site of infection. Using a mouse model of oropharyngeal candidiasis (OPC), we found that strikingly the IL-17 pathway is not required for the neutrophil response to C. albicans. Mice deficient for the IL-17 receptor subunits IL-17 receptor A (IL-17RA) or IL-17RC or mice depleted of IL-17A and IL-17F exhibited a normal granulocyte colony-stimulating factor (G-CSF) and CXC-chemokine response and displayed no defect in neutrophil recruitment or function. Instead, the inability of these mice to clear the fungus was associated with a selective defect in the induction of antimicrobial peptides (AMPs) in the epithelium that resulted in persistent fungal colonization. Importantly, this antifungal mechanism of IL-17A and IL-17F did not extend to the closely related family member IL-17C. Together, these data uncouple IL-17-dependent effector mechanisms from the neutrophil response and reveal a compartmentalization of the antifungal defense in the oral mucosa providing a new understanding of IL-17-mediated mucosal immunity against C. albicans.

Phase IV study of the injection Norigest in Pakistan.

A field study of the injectable contraceptive, norethisterone enanthate (NET-EN), was conducted in family planning clinics in Sind and Punjab provinces of Pakistan, to determine the acceptability and feasibility of providing NET-EN in government family planning clinics staffed by Family Welfare Visitors (FWVs). A total of 2147 women were recruited to the study, of whom approximately three-fourths had never previously used contraception. The overall discontinuation rate at one year was 78 per 100 women; the most common reason for discontinuation was bleeding disturbances, including amenorrhea, although returning to the clinic too late for an injection also accounted for a substantial proportion of the discontinuations. Given adequate training, FWVs were shown to be capable of providing NET-EN in family planning clinics, including managing the bleeding disturbances common with this method of contraception. No pregnancies were reported, demonstrating that the method is highly effective when used in a usual family planning clinic situation.

A clinical study of norethisterone enanthate in rural Mexico.

Clinical trials of norethisterone enanthate (NET-EN), a long-acting, injectable progestogen, have demonstrated its short-term safety and effectiveness as a method of contraception in a controlled trial setting. Family planning programs interested in providing NET-EN need information on its efficacy and acceptability under usual field conditions. This first field study of NET-EN was conducted in family planning clinics in rural areas of Mexico. Women admitted to the study were followed up at two-month intervals to receive an injection of 200 milligrams of NET-EN, and to be asked about possible side effects of the drug. Among the 5,792 women recruited, the overall life-table discontinuation rate was 57.0 per 100 women at 12 months and 69.0 at 18 months. The single most common reason for discontinuation was amenorrhea, followed by bleeding problems. Women who were older and who already had several children were most likely to continue using NET-EN. Nine pregnancies were reported during the study, with a cumulative pregnancy rate of 0.3 per 100 women at 18 months. NET-EN appears to be an effective method of contraception that is acceptable to a substantial proportion of women from rural areas in Mexico who choose to use it, when it is provided through a national family planning program.

Vaginal bleeding disturbances associated with the discontinuation of long-acting injectable contraceptives. From the World Health Organization Special Programme for Research, Development, and Research Training in Human Reproduction; Task Force on Long-acting Systemic Agents for the Regulation of Fertility.

A randomized comparative trial of 832 women receiving norethisterone oenanthate (NET-OEN) and 846 women receiving depot medroxyprogesterone acetate (DMPA) injections at 12 week intervals was conducted in 10 centers. The pregnancy rate with NET-OEN was significantly higher than with DMPA. The termination rate for amenorrhoea was substantially lowe with NET-OEN than DMPA, whereas the discontinuation rates for bleeding problems were similar with the two drugs. Analysis of bleeding patterns among continuing and discontinuing users suggests that women tolerated frequent bleeding episodes, but found prolonged bleeding or prolonged bleeding-free intervals unacceptable. Bleeding for more than 30 days during an injection interval and complete amenorrhoea for a whole injection interval were jointly associated with 43.7% of all terminations among NET-OEN users and 64.5% of all terminations among DMPA users. In future efforts to improve the acceptability of long-acting injectable contraceptives, more attention should be given to the control of prolonged amenorrhoea and prolonged bleeding.

PIP: A randomized comparative trial of 832 women receiving (NET-EN) norethisterone enanthate and 846 women receiving (DMPA) depot medroxyprogesterone acetate injections at 12 week intervals was conducted in 10 centers. The pregnancy rate with NET-EN was significantly higher than with DMPA. The termination rate for amenorrhea was substantially lower with NET-EN than DMPA, whereas the discontinuation rates for bleeding problems were similar with the 2 drugs. Analysis of bleeding patterns among continuing and discontinuing users suggests that women tolerated frequent bleeding episodes, but found prolonged bleeding or prolonged bleeding-free intervals unacceptable. Bleeding for more than 30 days during an injection interval and complete amenorrhea for a whole injection interval were jointly associated with 43.7% of all terminations among NET-EN users and 64.5% of all terminations among DMPA users. In future efforts to improve the acceptability of long acting injectable contraceptives, more attention should be given to the control of prolonged amenorrhea and prolonged bleeding.

Characteristics of the spread of a wildlife rabies epidemic in Europe.

The control of rabies in wildlife by reducing the fox population has led in Europe to inconsistent results, since little was known of the dynamics of the fox population and the interaction between rabies epidemics, host populations, and control measures. As part of the WHO/FAO Coordinated Research Programme on Wildlife Rabies in Europe, data on epidemics and persisting reservoirs of the disease were processed by computer. The results led to a better understanding of the mechanism of spread of the epidemic and to proposals for the improvement of rabies control in animals and the protection of man.