Tuberculosis is one of the most important infectious diseases in the world. Only 68% of the estimated new tuberculosis (TB) cases in Brazil are diagnosed. Our aim was to determine the risk of infection among household contacts. Study design. Cohort of tuberculin-negative household contacts followed for 12 Months. Methods. Household contacts of randomly selected index acid-fast bacilli (AFB)-positive TB cases were evaluated through clinical examination, thorax X-ray, tuberculin, AFB smear and culture. Contacts with a negative response to the tuberculin test (less than 10 mm diameter) were retested after 90 days. Tuberculin reversal (used as a parameter of infection risk) was defined as an increase of at least 10 mm from the last measurement. Results. 269 household contacts were followed. The prevalence of disease in this population was 3.7%. The prevalence of infection after the 12-month follow-up period was 63.9%. The risk of infection was 31.1% within 120 ± 48 days. Conclusion. Household contacts of AFB positive tuberculosis patients have a very high prevalence and risk of tuberculosis infection. TB preventive or therapeutic measures directed towards this group should be implemented in Brazil.

Forty-nine AIDS patients, most of who were antiretroviral therapy (ARV) naïve, with active tuberculosis, were treated with Rifampin 600mg, Isoniazid 400mg and Pirazinamide 2g daily. They also received ARV, consisting of Efavirenz (600mg/day) plus 2 NRTIs. All patients were prospectively followed for at least 24 months. Baselines were: male/female ratio 2:1, mean age 34.7 ± 9.4 yrs; weight 51 ± 9.0 kg, viral load 5.6 ± 0.6 logs, CD4 cell count 101 ± 128 cells/ mm³. Follow up mean values of data logs of VL and CD4+ cell /mm³ counts were: VL 1.7 and CD4+ 265; VL 1.3 and CD4+ 251; VL 1.4 and CD4+ 326 at 6, 12 and 24 months, respectively. Weight gain changes were: 5 ± 9.9 ± 12 and 21 ± 16 kg respectively at 6, 12 and 24 months. A non-concomitant ARV regimen was introduced at least three weeks after TB treatment initiation. Severe adverse reactions included rash (two), toxic hepatitis (six), Immune Reconstitution Syndrome (seven), and four deaths. We conclude that Efavirenz at a daily dose of 600 mg is sufficient and safe to treat HIV/TB patients using a Rifampin containing regimen.

It has been postulated that deficient or incomplete clinical and/or microbiological response to tuberculosis treatment is associated with cell-mediated immunological dysfunction involving monocytes and macrophages. A phase 2 safety trial was conducted by treating patients with either recombinant human granulocyte-macrophage colony-stimulating factor (rhu-GM-CSF) or a placebo, both in combination with anti-tuberculosis chemotherapy. Thirty-one patients with documented pulmonary tuberculosis were treated with rifampin/isoniazid for six months, plus pyrazinamide for the first two months. At the beginning of treatment, rhu-GM-CSF (125µg/M²) was randomly assigned to 16 patients and injected subcutaneously twice weekly for four weeks; the other 15 patients received a placebo. The patients were accompanied in the hospital for two weeks, then monthly on an out patient basis, for 12 months. Clinical outcomes were similar in both groups, with no difference in acid-fast bacilli (AFB) clearance in sputum at the end of the fourth week of treatment. Nevertheless, a trend to faster conversion to negative was observed in the rhu-GM-CSF group until the eighth week of treatment (p=0.07), after which all patients converted to AFB negative. Adverse events in the rhu-GM-CSF group were local skin inflammation and an increase in the leukocyte count after each injection, returning to normal 72 hours after rhu-GM-CSF injection. Three patients developed SGOP and SGPT > 2.5 times the normal values. All patients included in the GM-CSF group were culture negative at six months, except one who had primary TB resistance. None of the patients had to discontinue the treatment in either group. We conclude that rhu-GM-CSF adjuvant immunotherapy could be safely explored in a phase 3 trial with patients who have active tuberculosis.

Sulfonamides are drugs extensively used in the management of AIDS patients. However, the use of sulfonamides is often associated with the development of allergic reactions, provoking the substitution of the drug (by another that may be less effective); alternatively attempts are made to desensitize the patient. OBJECTIVE: Compare two drug regimens (full vs. escalating doses) for the oral desensitization of AIDS patients allergic to sulfonamides. MATERIAL AND METHODS: AIDS patients with previous allergic reactions to sulfonamides and requiring prophylaxis against Pneumocistis carinii, central nervous system toxoplasmosis and diarrhea caused by Isospora belli were randomly assigned to a group receiving a routine dose of cothrimoxazole, or another that received escalating doses of an oral suspension of the same drug, initiating with 75mg/day of sulfamethoxazole that was doubled every 48 hours till the full dose was reached, if no allergic reaction occurred. Patients were monitored for at least 6 months after enrollment in the trial. The major end-point was the ability to maintain prophylactic treatment after that period of time. Plasma viral load (PVL) and CD4/CD8 counts were measured at baseline. Liver enzymes and hematological parameters were measured at baseline and after 1, 3 and 6 months. RESULTS: Eighteen patients were enrolled in the study (15 men and 3 women), with ages ranging from 30 to 57 years (mean 39.9). The mean CD4 counts were slightly higher for patients receiving a full dose; there was also a trend towards higher baseline CD8 counts among patients developing new reactions. The mean PVL was similar among the patients in both desensitization groups. The incidence of new allergic reactions was identical (40%) in the two groups. All adverse reactions were mild and no significant increase in liver enzymes were observed. CONCLUSON: Dose regimen is not a predictor of the development of new allergic reactions amongst patients challenged with sulfonamides after an initial allergic reaction.