Two-stage activity-safety study of daily rifapentine during intensive phase treatment of pulmonary tuberculosis.

BACKGROUND: Rifapentine (RPT) has potent activity against Mycobacterium tuberculosis; however, the optimal dose for anti-tuberculosis treatment is unknown. OBJECTIVE: To determine the antimicrobial activity, safety and tolerability of RPT 450 mg or 600 mg administered daily during the first 8 weeks of treatment for pulmonary tuberculosis (TB). DESIGN: In a two-stage, randomised open-label study, adults with sputum smear-positive TB were randomised to receive RPT 450 mg, RPT 600 mg or rifampicin (RMP) 600 mg daily for 8 weeks with isoniazid, pyrazinamide and ethambutol. The primary endpoint was sputum culture status on Löwenstein-Jensen (LJ) medium at completion of 8 weeks of treatment. RESULTS: A total of 153 participants were enrolled. Both RPT regimens met pre-specified criteria to advance to stage 2. At completion of 8 weeks of treatment, LJ culture conversion occurred in 85% (35/41), 96% (43/45) and 94% (34/36) of participants in the RPT 450 mg, RPT 600 mg and RMP groups, respectively. The proportions of participants discontinuing treatment were similar (respectively 1/54 [2.0%], 1/51 [2.0%] and 4/48 [8.3%] in the RPT 450 mg, RPT 600 mg and RMP groups), as were ⩾grade 3 adverse events (0/54 [0%], 1/51 [2.0%] and 4/48 [8.3%]). CONCLUSIONS: There was a trend towards greater efficacy with RPT 600 mg than with RPT 450 mg. Daily RPT was safe and well-tolerated.

Tuberculosis control in a socially vulnerable area: a community intervention beyond DOT in a Brazilian favela.

OBJECTIVES: To evaluate the population-based impact of a comprehensive intervention to strengthen tuberculosis (TB) control in Rocinha, the largest urban slum in Rio de Janeiro, Brazil. DESIGN: In July 2003, 40 lay persons were hired and trained as community health workers to supervise treatment, implement educational activities and establish a supportive social network for anti-tuberculosis treatment. Between July 2005 and June 2008, a door-to-door active case finding campaign was conducted. Data were obtained from the Brazilian National Reporting System, which collects information from the TB notification form for every reported case. RESULTS: Between January 2001 and December 2008, 2623 TB cases were reported, 852 before and 1771 after the start of the program. Following the intervention, treatment success rates increased (67.6% vs. 83.2%, P < 0.001) and default rates dropped (17.8% vs. 5.5%, P < 0.001). Compared to the pre-intervention period, the TB case rate declined by an average of 39 cases per 100,000 population per 6 months (P = 0.003) in the post-intervention period, although this may have been due to secular trends already in place at the start of the intervention. Case rates declined from 591/100,000 in 2001 to 496/100,000 in 2008. CONCLUSION: With proper planning and effective community involvement, a successful intervention can lead to high cure rates and may contribute to a decrease in TB notification rates.

A serological and bacteriological survey of dogs to detect Brucella infection in Lomas de Zamora, Buenos Aires province.

Canine brucellosis caused by Brucella canis is a disease of the reproductive tract that may cause miscarriage in females, infection of the sexual organs in males and infertility in both sexes. The prevalence of brucellosis in dogs is unknown and little has been done to control the disease, except in certain breeds and some commercial dog kennels. In the course of a free neuter program in Lomas de Zamora, Buenos Aires province, prevalence of antibodies to Brucella sp., bacteriological isolation and clinical observations were performed. Of 224 dogs studied, 33 (14.7%) were found positive for the rapid slide agglutination test (RSAT), 24 (10.7%) of which were confirmed by IELISA. Of the 33 RSAT positive, 17 (51.5%) blood cultures were done, and B. canis were isolated from 2 cases. Since infected dogs have been shown to remain bacteremic for prolonged periods, our results also suggest a risk of human infections in this area.

Tuberculosis incidence among contacts of active pulmonary tuberculosis.

BACKGROUND: Treatment of latent tuberculosis (TB) infection (LTBI) in Brazil is recommended only in the case of contacts of pulmonary smear-positive TB patients agedor=10 mm and no previous bacille Calmette-Guérin (BCG) vaccination or with a TST>or=15 mm regardless of previous BCG vaccination. OBJECTIVE: To evaluate the 2-year incidence and predictors of TB among contacts who did not meet the Brazilian criteria for LTBI treatment. DESIGN: Retrospective cohort study. Contacts aged between 12 and 15 years and those aged>or=15 years who did not meet the Brazilian criteria for LTBI treatment were enrolled in the study. RESULTS: TB incidence was 3.2% (22/667), with an estimated TB rate of 1649 per 100000 population. Risk of TB was greater among the 349 contacts with TST>or=5 mm (5.4%) compared to the 318 contacts with TST<5 mm (0.9%; RR 6.04, 95%CI 1.7-20.6). CONCLUSION: The high incidence of TB among contacts who did not meet the Brazilian criteria for LTBI treatment strongly suggests that these criteria should be reviewed. Furthermore, even among BCG-vaccinated contacts, TST induration>or=5 mm was the only variable that predicted the development of TB disease within 2years.

Idiopathic giant-cell granulomatous hypophysitis mimicking acute meningitis.

A 32-year-old woman presented with severe headache, photophobia, fever, nausea, vomiting, and worsening vision. She had also noted several months of amenorrhea. She was febrile to 38.9 degrees C. Laboratory evaluation revealed a markedly elevated erythrocyte sedimentation rate. Lumbar puncture revealed a cerebrospinal fluid lymphocytic pleocytosis and an elevated protein level. Endocrine studies revealed evidence of panhypopituitarism without diabetes insipidus. A magnetic resonance imaging study showed a 2-cm pituitary mass with optic chiasmal compression. The patient had a trans-sphenoidal resection of the mass. Pathology revealed multinucleated giant cells in necrotic debris, but no evidence of pituitary tumor. Studies looking for evidence of systemic granulomatous disease were negative. The patient was considered to have idiopathic giant-cell granulomatous hypophysitis. After surgery, the patient's vision improved and hormone replacement therapy was initiated. This case illustrates that idiopathic giant-cell granulomatous hypophysitis should be considered in the differential diagnosis of a patient presenting with a pituitary mass, hypopituitarism, and meningitis-like symptoms.

Human infection by Brucella melitensis: an outbreak attributed to contact with infected goats.

Although several outbreaks of Brucella melitensis infection have been reported among laboratory workers or goat cheese consumers, outbreaks related to rural labour have been rarely studied. An outbreak of human brucellosis among farm workers of Argentina was studied and revealed a close relationship with an epidemic of caprine abortions which occurred shortly before on the same farm. High rates of B. melitensis infection were found among goats. Active brucellosis was diagnosed in 33 subjects (14 with positive blood culture for B. melitensis), while other 27 did not show evidence of illness. While 25 of the brucellosis active patients were rural workers, only 5 of the healthy subjects were engaged in rural labour. Active brucellosis was diagnosed in 91.3% of the subjects in continuous contact with goats and in 32% of those having an occasional contact with the animals. All the 60 subjects denied consumption of goat cheese or milk. As shown here, epidemic human infections by B. melitensis may develop among people frequently in contact with infected goat herds or goat manure.

Offspring of patients with affective disorders.

All the children (ages 5-15) of 14 consecutive patients admitted to hospital at the National Institute of Mental Health with a diagnosis of bipolar or unipolar affective disorder were studied. The children were seen twice, four months apart, and assessed by an interview and rating scales. The parents were also assessed. Of 14 boys, five were depressed on both interviews and three were depressed on one interview. Four of the 16 girls were depressed on both interviews and 11 were depressed on one interview. The clinical picture and the ratings showed the boys, but not the girls, to have a significant correlation for depression on both interviews. The children diagnosed as suffering from depression showed the symptoms of a primary unipolar affective disorder without other significant pathology.