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To evaluate the risk of developing active tuberculosis (TB) in a cohort of HIV-1-infected patients.Prospective longitudinal follow-up of 839 HIV-infected patients, of whom 505 (60%) were parenteral drug users and 269 (32%) homosexual men. Tuberculin skin tests were performed at baseline and annually thereafter. Prophylaxis with isoniazid (300 mg daily for 9 months) was offered to those with a positive tuberculin test (indurationor = 5 mm). Diagnosis of TB was accepted if it could be confirmed microbiologically (acid-fast bacilli seen in Ziehl-Neelsen stains or grown in Lowenstein-Jensen cultures) or pathologically (presence of caseating granulomas) and patients had consistent clinical manifestations.Active TB developed in 23 out of the 733 (3.1%) patients with a negative tuberculin skin test after a mean follow-up of 16 +/- 11 months (range, 2-52 months), with an estimated cumulative probability of 1.5 and 7% after 1 and 3 years, respectively (or 2.4 per 100 patient-years). None of the 87 patients with a negative tuberculin test but a positive Multitest developed TB. Conversely, 106 patients had a positive tuberculin skin test (97 at baseline and nine who converted during follow-up). Active TB developed in seven out of the 26 not receiving prophylaxis or in whom prophylaxis had to be discontinued (16.2 per 100 patient-years), in four out of 61 patients 3-27 months after having completed 9 months of prophylaxis with isoniazid (8.9 per 100 patient-years) and in none of the 19 still receiving isoniazid. When TB was diagnosed, the mean CD4 lymphocyte count of the 34 patients who developed it during follow-up was 77 +/- 103 x 10(6)/l (range, 1-400 x 10(6)/l).Among HIV-infected patients in whom the tuberculin skin test is negative, the risk of developing active TB is sufficient to consider prophylaxis if the CD4 count falls below 400 x 10(6)/l, at least in those patients with skin anergy living in high-risk geographical areas such as Spain. When the tuberculin skin test was positive, isoniazid (9 months) provided a 45% protection beyond the period of its administration.This study sought to evaluate the risk of developing active tuberculosis (TB) in a cohort of HIV-1-infected patients. A prospective longitudinal follow-up was carried out on 839 HIV-infected patients, of whom 505 (60%) were parenteral drug users and 269 (32%) were homosexual men. Tuberculin skin tests were performed at baseline and annually thereafter. Prophylaxis with isoniazid (300 mg daily for 9 months) was offered to those with a positive tuberculin test (induration or= 5 mm.). Diagnosis of TB was accepted if it could be confirmed microbiologically (acid-fast bacilli seen in Ziehl-Neelsen stains or grown in Lowenstein-Jensen cultures) or pathologically (presence of caseating granulomas) and patients had consistent clinical manifestations. Active TB developed in 23 of the 733 (3.1%) patients with a negative tuberculin skin test after a mean follow-up of 16 +or- 11 months (range, 2-52 months), with an estimated cumulative probability of 1.5 and 7% after 1 and 3 years, respectively (or 2.4 per 100 patient-years). None of the 87 patients with a negative tuberculin test, but a positive Multitest, developed TB. Conversely, 106 patients had a positive tuberculin skin test (97 at baseline and 9 who converted during follow-up). Active TB developed in 7 of the 26 not receiving prophylaxis or in whom prophylaxis had to be discontinued (16.2 per 100 patient-years), in 4 of 61 patients 3-27 months after having completed 9 months of prophylaxis with isoniazid (8.9 per 100 patient-years), and in none of the 19 still receiving isoniazid. When TB was diagnosed, the mean CD4 lymphocyte count of the 34 patients who developed it during follow-up was 77 +or- 103 x 106/L (range, 1-400 x 106/L). Among HIV-infected patients in whom the tuberculin skin test is negative, the risk of developing active TB is sufficient to consider prophylaxis if the CD4 count falls below 400 x 106/L, at least in those patients with skin anergy living in high-risk geographical areas such as Spain. When the tuberculin skin test was positive, isoniazid (9 months) provided a 45% protection beyond the period of its administration.

Rickettsiae are pleoniorphocic, obligate intracellular bacteria that occur in the form of cocci and fdaments. They are the cause of widespread disease in tropical and temperate parts of the world. Spotted fever attributable to Rickettsia conorii is a zoonosis transmitted to man by the bite of the dog tick, Rkipicephalus ranpineus. Recently, the incidence in endemic areas has been increasing,'.* and cases have been reported in areas where the disease was previously unusual or unknown. Characteristic features of the disease are fever, headache, myalgia, eschar at the site of the tick bite, and maculopapular rash. The illness is similar to Rocky Mountain spotted fever with two main differences: (1) eschar is present in 30-90% of SFRC patient^,^,^ and (2) SFRC is usually milder, although fatalities have occurred.','." During the period 1991-1993, the authors diagnosed ten patients with SFRC. In all cases, the disease occurred after a recent visit to SubSaharan Africa. The diagnosis was made by consideration of clinical and epidemiologic findings (fever, eschar, rash, and recent travel to an endemic area). Serologic testing revealed positive Igh4 titer or a fourfold titer rise to R. conorii by immunofluorescence assay (IFA). The illness had been acquired in all cases during a trip of G14 days (average 10.8) to SubSaharan Ai it accounts for the majority of imported rickettsioses.' Without efforts at risk reduction, the number of travelers at risk for SFRC is likely to increase as more people go on safari in Africa. The presence of an eschar is valuable in making the diagnosis, and its presence is noticed in 30-90% of reported If an eschar is absent, diagnosis of SFRC is more difficult, and causes of febrile exanthem must be considered in the differential diagnosis.The frequencies of fever, rash, eschar, myalgias, and headaches in our patients were similar to those in other published The patient without fever had two eschars,rash,and positive IgM antibodies. One patient presented with pneumonia, an uncommon complication of SFRC.' The increase in serum aspartate aminotransaminase in 40% of our cases is similar to the frequency reported in other series.' SFRC can be confirmed by the isolation of the organism in an eschar or maculopapular lesion by immunofluorescence or by specific serologic assessment

Objective : To evaluate the efficacy of twice-weekly maintenance therapy with sulfadiazine-pyrimethamine to prevent toxoplasmic encephalitis relapse in patients with the acquired immunodeficiency syndrome (AIDS). . Design : Randomized, open, multicenter trial. Patients were randomly assigned to receive sulfadiazine (500 mg) four times per day plus pyrimethamine (25 mg) plus folinic acid (15 mg) either daily (n = 60) or twice weekly (n = 45). . Setting : 8 university teaching hospitals. . Patients : Between February 1990 and June 1993, 105 patients with HIV infection were enrolled after each had had resolution of an acute episode of toxoplasmic encephalitis treated with sulfadiazine (1 g four times per day) plus pyrimethamine (50 mg/d) plus folinic acid (15 mg/d) for 4 to 8 weeks. . Measurements : Clinical and biological evaluations done every 30 to 60 days. End points were toxoplasmic encephalitis relapse, death, and interruption of therapy due to adverse reactions. . Results : After a median follow-up period of 11 months (range, 1 to 39 months), patients receiving the twice-weekly regimen had a higher rate of relapse than patients receiving the daily regimen (19.5 compared with 4.4 per 100 patient-years ; incidence rate ratio, 4.36 [95% Cl, 1.05 to 25.5] ; P= 0.024). The estimated cumulative percentages of relapse at 12 months were 30% and 6%, respectively (P = 0.029), with an adjusted risk ratio (adjusted for age, sex, risk behavior, previous diagnosis of AIDS, Pneumocystis carinii pneumonia prophylaxis before initial episode of toxoplasmosis, CD4 cell count, baseline number of brain lesions, radiologic sequelae, and antiretroviral therapy during follow-up) of 5.6 (Cl, 1.2 to 25.6 ; P = 0.028). Patients receiving the twice-weekly regimen had 1.6 times (Cl, 0.9 to 2.9 times ; P = 0.11) the adjusted risk for death of patients receiving the daily regimen. No statistical differences were found in the patients who stopped receiving the regimens due to adverse effects. No patient developed P. carinii pneumonia during the study period, even though 17 patients (10 receiving the daily regimen and 7 receiving the twice-weekly regimen) had had an episode of P. carinii pneumonia before study entry. . Conclusions : At the given doses, a combination of sulfadiazine, pyrimethamine, and folinic acid was less effective when administered twice weekly than when administered daily, although the twice-weekly regimen was much more effective than historic controls.

This study evaluated the efficacy of switching to didanosine in patients who were clinically or immunologically progressing despite zidovudine therapy. This multicenter, open-label study involved 400 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC), who had tolerated zidovudine for at least 12 weeks and had signs of clinical or immunological disease progression. They were randomly assigned to receive 600 mg/d of zidovudine (n=133), 500 mg/d of didanosine (n=131), or 200 mg/d of didanosine (n=136). The primary end point was a new AIDS-defining event or death. The study was prematurely terminated, after the first interim analysis, mainly owing to results of two controlled studies demonstrating that a change to didanosine was associated with an improved outcome in patients with advanced HIV-1 disease. The median duration of follow-up was 53 weeks. The primary end point rates were 41, 58, and 59 (per 100 person-years) in the didanosine 500 mg, didanosine 200 mg, and zidovudine groups (zidovudine vs. didanosine 500 mg, relative risk 1.28, 95% confidence interval, 0.88-1.86, p = 0.19; didanosine 200 vs. 500 mg, relative risk 1.24, 95% confidence interval, 0.85-1.79, p = 0.26). In subjects with a baseline CD4 count of 100/mm3 or more, the primary end point rates were 8, 29, and 25 (per 100 person-years) in the didanosine 500 mg, didanosine 200 mg, and zidovudine groups, respectively (zidovudine vs. didanosine 500 mg, relative risk 2.96, 95% confidence interval 0.91-9.62, p = 0.07). No difference was seen in survival. In the didanosine 500 mg group, more patients had a 50% increase in CD4 cells (10% vs. 1% in zidovudine group, p = 0.01) and an increase of > or = 2.5 kg in body weight (2% versus 3%). Fatal pancreatitis developed in one patient assigned to didanosine 500 mg and in one to zidovudine. Our data suggest that switching from zidovudine to currently recommended doses of didanosine in subjects with ARC or AIDS who show evidence of clinical and laboratory disease progression can be associated with improvements in clinical outcome as well as in surrogate markers of HIV disease progression. This effect tended to be greater among individuals with higher CD4 counts (>100/mm3).