Can we use a lower intravaginal dose of misoprostol in the medical management of miscarriage? A randomised controlled study.

BACKGROUND: The optimal dose of misoprostol to be used in the medical management of miscarriage before 13 weeks has not been resolved. AIM: To evaluate the effectiveness and side effect profile of two different dosages of misoprostol. METHODS: A randomised controlled, equivalence study comparing 400 vs 800 µg misoprostol per vaginum (PV) on an outpatient basis. The allocated dose was repeated the next day if clinically the products of conception had not been passed. Complete miscarriage was evaluated using two methods: ultrasound criteria on Day 7 and the need for surgical management (clinical criteria). Equivalence was demonstrated if the 95% confidence interval [CI] of the observed risk difference between the two doses for complete miscarriage lay between -15.0 and 15.0%. Differences in side effects and patient satisfaction were evaluated using patient-completed questionnaires. RESULTS: One hundred and fifty-eight women were allocated to receive 400 µg and 152 women to 800 µg misoprostol for the management of missed (91.3%) or incomplete (8.7%) miscarriage. The rate of induced complete miscarriage was equivalent using both ultrasound criteria (observed risk difference (ORD) -4.6%, 95% CI -12.8 to 3.7%; P = 0.313) and clinical criteria (ORD -5.6%, 95% CI -14.8 to 3.6%; P = 0.273). Following the 400 µg dose, the reported rate of fever/rigors was lower (ORD -15.6%, 95% CI -28.1 to -3.0%; P = 0.015), and more women reported their decision to undergo medical management as a good decision (ORD 15.2%, 95% CI 2.8 to 27.7%; P = 0.018). CONCLUSION: Four hundred-microgram misoprostol PV can be recommended for the medical management of miscarriage on an outpatient basis.

Clinical strains of Mycobacterium tuberculosis display a wide range of virulence in guinea pigs.

Virtually all new tuberculosis vaccine candidates are tested in animals using the laboratory strains H37Rv or Erdman. However, naturally occurring M. tuberculosis infections are caused by strains that are widely different in phenotype and genotype. Very little is known about the characteristics of these clinical isolates in terms of basic biology, virulence and in vivo pathogenicity. In this study, we have used a standardized aerosol infection of guinea pigs to compare in vivo differences between clinical strains of M. tuberculosis. Strains consisted of both drug sensitive and multi-drug resistant (MDR) strains of Beijing and non-Beijing varieties. Collectively, these clinical isolates tested in the guinea pig model exhibited a wide range of virulence. Infection with certain isolates caused severe and rapidly progressive pulmonary and extra-pulmonary lesion necrosis, some of which progressed to atypical cavitary lesions in draining mediastinal and tracheobronchial lymph nodes. The two MDR-TB strains used in this study exhibited low level virulence as determined by bacterial growth, lesion scores and survival. Since infections with clinical M. tuberculosis isolates produce such varied disease, it is unknown whether new tuberculosis vaccines being developed will provide the same level of protection as seen when tested using laboratory challenge strains. The use of appropriate animal models allows for this important question to be addressed.

Cough-generated aerosols of Mycobacterium tuberculosis: a new method to study infectiousness.

The concentration and size distribution of infectious aerosols produced by patients with pulmonary tuberculosis (TB) has never been directly measured. We aimed to assess the feasibility of a method that we developed to collect and quantify culturable cough-generated aerosols of Mycobacterium tuberculosis. Subjects were recruited from a referral hospital and most had multidrug-resistant TB. They coughed into a chamber containing microbial air samplers while cough frequency was measured during two 5-minute sessions. Cough-generated aerosol cultures were positive in 4 of 16 subjects (25%) with smear-positive pulmonary TB. There was a rapid decrease in the cough-generated aerosol cultures within the first 3 weeks of effective treatment. Culture-positive cough aerosols were associated with lack of treatment during the previous week (p = 0.007), and there was a trend in the association with cough frequency (p = 0.08). The size distributions of these aerosols were variable, but most particle sizes were in the respirable range. Quantification of viable cough-generated aerosols is feasible and offers a new approach to study infectiousness and transmission of M. tuberculosis and other airborne pathogens.