Use of rhu-GM-CSF in pulmonary tuberculosis patients: results of a randomized clinical trial

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 (125æg/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

Cladophialophora bantiana (Previously Cladosporium trichoids): First report of a case in Brazil

Cladophialophora bantiana (Cladosporium trichoides) is a black fungus recorded rarely as a cause of brain abscess. Only 21 cases have been reported in the literature world-wide. We describe the first case seen in Brazil. A 30 year old, previously healthy female, HIV negative, came to the hospital with a clinical diagnosis of brain tumor. After biopsy and culture of the lesion, it was found that she had an abscess due to Cladosporium trichoides. During the following five months, the patient underwent three more surgical brain interventions to totally remove the area of compromised tissue. In addition to surgery, amphotericin B, both intravenously and intrathecally, was used followed by itraconazole orally, without sucess. Six months after the first surgical intervention, the patient died. The worldwide experience with diagnosis and treatment of patients with this diseases is reviewed.

Use od standard therapy for tuberculosis in associated with increased adverse reactions in patients with HIV

Hepatitis due to anti-tuberculosis therapy in an infrequent, but potentially devastating event. In HIV positive patients with tuberculosis (TB), the consequences are likely to be even greater, as they frequently require other hepatoptoxic medications. The object of our study was to determine the frequency to toxic hepatitis during therapy for TB. Included were 198 patients with a presumed or confirmed diagnosis of tuberculosis; of whom, 69 were HIV positive (35 percent), 75 were negative (38 percent) and 54 had unknown HIV status (27 percent). Toxic hepatitis occurred in 15/198 (8 percent) patients. The incidence of hepatitis in HIV patients was much greater than in HIV negative/unknown [RR=7.5 (2.2-25.6); p=0.0001] and the onset of hepatitis was short (median 7 days in HIV patients). During TB therapy, 1 in 8 (12.5 percent) patients taking ketoconazele developed hepatitis; 9/53 (17 percent) taking sulfamethoxazole-trimethoprim [RR=3.4 (1.1-9.3); p=0.03]. Among the 15 patients who developed hepatitis 11 required hospitalization (mean 19 days), 5 dfied (33.3 percent), 2/15 (13 percent) due to hepatitis. HIV positive patients had a significantly higher rate of toxic hepatitis during anti-tuberculosis therapy than those without HIV infection. Hepatitis occurred just after initiation of TB treatment. Clinical findings were non-specific and hepatic enzyme elevations were moderate, yet hospitalization and mortality rates were high. This suggests that in settings where careful monitoring of patients early in their course of TB treatment is routine, morbibity and mortality may be loe, but poor monitoring would have potentially serious consequences. There is a need for new drug treatments (schedules or regimens) for TB in an effort to reduce these adverse events.

Co-infection of tuberculosis and HIV/HTLV retroviruses: Frequency and prognosis among patients admitted in a Brazilian hospital

During 2½ year period, 378 patients diagnosed with tuberculosis and admitted to a general hospital for care of the poor in Salvador, Bahia, were tested serologically for HIV-1, HTLV-I, and HTLV-II. The patients' mean age was 41.8 (range 14-89); they were hospitalized for a mean of 62 ñ 43 days; 70 percent were being treated for the first time; most of the remainder were being retreated after non-compliance with previously recommended anti-tuberculosis medication and a few required second-line therapy for relapsed disease. None had had previous serologic testing for retroviruses. Among the study population, 59 (16 percent) were found to be positive for retroviral infection. The distribution was as follows: 18 (4.8 percent) had HIV-1, 32 (8.5 percent) had HTLV-I, 2 of these had both HTLV-I and HTLV-II, 9 (2.4 percent) had both HIV-1 and HTLV-I. The rates of positive serologic tests for retroviral infection in this Salvador is 0.2 percent for HIV-1 and 1.0 percent for HTLV-I. Thus, there is a higher than expected frequency of retroviral infections among patients hospitalized for treatment of tuberculosis. The prognosis for treated patients was determined by recording the cause of death and the mortality rate. In the 319 patients with negative serologic testing for retroviruses the were 25 death (8 percent). In 32 patients with HTLV-I infection there were 8 death (25 prcent), and in 18 patients with HIV-1 infection there were 6 deaths (33 percent). In 9 patients with both HIV-1 and HTLV-I there were 5 deaths (56 percent). The causes of death in each serological group were primarily related to progression of tuberculosis rather than complications of rapid progression of the retroviral infection. We conclude that co-infection and disease due to either HIV-1 or HTLV-I/II infection and tuberculosis is common, that the ocurrence of HTLV-I in this population is higher than previously recognized, and that prognosis associated with the management of tuberculosis is adversely affected by the presence of either retroviral infection. In a few patients with both retroviral infections, mortality was very high. All patients with tuberculosis should be tested for retroviral infection because of the prognostic and therapeutic implications.

Aedes aegypti surveillance and correlation with the occurrence of dengue fever in Bahia, Brazil

Due to the high frequency of dengue fever cases and the presumed association of such an epidemic with an increase in the population of the mosquito vector, Aedes aegypti, we examined the records of the Ministry of Health in the state of Bahia, Brazil, regarding the monitoring of domestic mosquito larvae in municipalities throughout the state. The "House Index" number for larvae in domestic water reservoirs was determined for each municipality based on annual surveys from 1990 to 1994, and in 1996. In 1996, 69 percent of the municipalities surveyed in Bahia were positive, and 30 percent had indices above 5 percent. During 1990 and 1991, the level of larvae identified was low and stable; however, during November and December, 1992, a dramatic increase was recorded. The increase continued until 1996, when over 100-fold increases in house indices were recorded in Feira de Santana and Ilhéus, and 60-fold in Salvador. The dengue fever epidemic was documented in the region beginning in 1994. A strong correlation has been demonstrated between an increase in the mosquito larvae population and the emergence of dengue fever.