Heonir Rocha

Treatment of Visceral Leishmaniasis with Pentavalent Antimony and Interferon Gamma

Acute visceral leishmaniasis is associated with an antigen-specific immunosuppression of mononuclear cells as evidenced by defective in vitro production of interferon gamma. We evaluated treatment with recombinant human interferon gamma in combination with conventional pentavalent antimony therapy in patients with visceral leishmaniasis. Six of eight patients with visceral leishmaniasis (mean duration, 17 months) that had been unresponsive to multiple courses of pentavalent antimony responded to treatment with recombinant human interferon gamma (100 to 400 micrograms per square meter of body-surface area per day) in addition to pentavalent antimony (20 mg per kilogram of body weight per day) for 10 to 40 days. The other two patients improved initially but then relapsed and required treatment with amphotericin B. Eight of nine additional patients with previously untreated severe visceral leishmaniasis were also successfully treated with the combination of interferon gamma and pentavalent antimony. The 14 patients who responded to this regimen had marked improvement in symptoms and in measures of anemia and leukopenia, as well as weight gain, a decrease in spleen size, and an absence or reduction of leishmanias in splenic aspirates. These patients had no recurrence of illness after a mean (+/- SE) follow-up of 8 +/- 1 months. Fever was the only major side effect of interferon gamma. We conclude that the combination of interferon gamma and pentavalent antimony is effective in treating seriously ill patients with refractory or previously untreated visceral leishmaniasis.

Renal Involvement in Visceral Leishmaniasis

In a prospective study of 50 patients with visceral leishmaniasis, laboratory abnormalities suggestive of renal involvement were not infrequent. Proteinuria and/or microscopic hematuria or pyuria were observed in 51% of such cases. Twenty-four hour urinary protein excretion was elevated in 57% of patients in all cases below 1g/24 hours. An abnormal acid-load test was demonstrated in 12 of 18 patients studied before therapy of the parasitic infection with N-methyl-glucamine. Of interest was the demonstration of tubulo-interstitial involvement in the renal histology of all seven patients studied; also, in five of seven patients there was a proliferative glomerulonephritis, usually mild, on histologic examination. In general, there was a tendency to subsidence of abnormal laboratory findings within one month after specific therapy. Renal involvement in visceral leishmaniasis was mild and seemed to revert with the cure of the leishmanial infection.

Primary focal segmental glomerulosclerosis in children: prognostic factors

Abstract To study the clinical course and the predictors of outcome in children and adolescents, 39 patients with nephrotic syndrome and primary focal segmental glomerulosclerosis (FSGS) were followed for a mean of 84.6 months. Thirty-six patients were treated with prednisone, either alone or in conjunction with cyclophosphamide. The clinical course was one of sustained remission in 4 patients, frequent relapse in 13, persistent non-nephrotic proteinuria in 5, and persistent nephrotic syndrome in 17; 2 patients had stable renal failure and 8 had progressive renal failure, 5 of them evolving to end-stage renal failure (ESRF). Resistance to prednisone was recorded in 76.6% of patients. The use of cyclophosphamide plus prednisone was of benefit in 42.8% of patients; 22.2% of the prednisone-resistant patients achiev-ed remission of the nephrotic syndrome. A Kaplan-Meier analysis revealed a survival rate of 92% after 5 years, 86% after 10 years, and 76% after 15 years. Using both univariate and multivariate analysis, persistent nephrotic syndrome was associated with progression to ESRF and the remission of proteinuria with maintenance of renal function. As the outcome of the nephrotic syndrome in FSGS is significantly improved by remission of proteinuria, it is conceivable that immunosuppressive medication may be used in conjunction with prednisone in patients with steroid resistance.

Clonally related penicillin-nonsusceptible Streptococcus pneumoniae serotype 14 from cases of meningitis in Salvador, Brazil.

Active hospital-based surveillance in the city of Salvador, Brazil, from December 1995 through October 1998, identified 221 patients with confirmed pneumococcal meningitis. Of these 221 patients, 29 (13%) had isolates with intermediate-level resistance to penicillin. Infection with these penicillin-nonsusceptible isolates was significantly associated with age of <2 years (P<.0019), previous antibiotic use (P<.0006), and coresistance to trimethoprim-sulfamethoxazole (P<.0000). Serotype 14 was the most prevalent serotype (55.2%) of penicillin-nonsusceptible isolates. Strain typing by repetitive element BOX polymerase chain reaction (PCR) analysis showed that penicillin-nonsusceptible serotype 14 isolates had closely related BOX PCR patterns, whereas penicillin-susceptible serotype 14 isolates each had distinct, unrelated patterns. Penicillin-nonsusceptible serotype 14 isolates from Salvador and other Brazilian cities had similar BOX PCR patterns. These observations indicate that in Brazil a large proportion of cases of penicillin-nonsusceptible pneumococcal meningitis appear to be caused by a closely related group of serotype 14 strains that may have disseminated to widely separate geographic areas.

Immunological features in different clinical forms of strongyloidiasis

Serum immunoglobulin levels, skin test response to PPD, lymphocyte surface markers and eosinophil count in peripheral blood were studied in 35 patients with strongyloidiasis diagnosed by stool examination. The patients were divided into three groups based on clinical history, physical examination and laboratory examination: an asymptomatic group (14 patients), a symptomatic group (14 patients) and a group with severe parasitic infection (seven patients). In three of the seven patients with severe strongyloidiasis, massive infection caused by Strongyloides stercoralis had been diagnosed at least once before this study. The IgG levels were significantly lower (p less than 0.05) in patients with severe strongyloidiasis (1180 +/- 529 mg/dl) than in the asymptomatic group (2347 +/- 1224). IgA and IgM levels were also lower in the patients with massive infection when compared to the asymptomatic and symptomatic groups. No decrease of T cells or B cells was found in patients with severe strongyloidiasis. However, the eosinophil count was significantly lower in patients with severe strongyloidiasis than in asymptomatic or symptomatic patients (p less than 0.05). The authors suggest that eosinophils and antibodies may play an important role in the defence mechanism against S. stercoralis larvae.

Comparison of ceftriaxone and ampicillin plus chloramphenicol for the therapy of acute bacterial meningitis.

Ceftriaxone, a new third-generation cephalosporin, appears to be promising for the therapy of acute bacterial meningitis. The 90% MBCs of ceftriaxone against 54 recent cerebrospinal fluid isolates of Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae were less than or equal to 0.06 to 0.25 micrograms/ml. We examined the efficacy and safety of ceftriaxone therapy of meningitis in Bahia, Brazil. The study was conducted in two phases; in phase A, ceftriaxone was coadministered with ampicillin. The mean cerebrospinal fluid concentrations of ceftriaxone 24 h after an intravenous dose of 80 mg/kg were 4.2 and 2.3 micrograms/ml on days 4 to 6 and 10 to 12 of therapy, respectively. These concentrations were 8- to more than 100-fold greater than the 90% MBCs against the relevant pathogens. In phase B, ceftriaxone (administered once daily at a dose of 80 mg/kg after an initial dose of 100 mg/kg) was compared with conventional dosages of ampicillin and chloramphenicol in a prospective randomized trial of 36 children and adults with meningitis. The groups were comparable based on clinical, laboratory, and etiological parameters. Ceftriaxone given once daily produced results equivalent to those obtained with ampicillin plus chloramphenicol, as judged by cure rate, case fatality ratio, resolution with sequelae, type and severity of sequelae, time to sterility of cerebrospinal fluid, and potentially drug-related adverse effects. The cerebrospinal fluid bactericidal titers obtained 16 to 24 h after ceftriaxone dosing were usually 1:512 to greater than 1:2,048 even late in the treatment course, compared with values of 1:8 to 1:32 in patients receiving ampicillin plus chloramphenicol. Ceftriaxone clearly deserves further evaluation for the therapy of meningitis; the optimal dose, dosing frequency (every 12 h or every 24 h), and duration of therapy remain to be determined.

Evaluation of T‐cell subsets in the lesion infiltrates of human cutaneous and mucocutaneous leishmaniasis

Summary We have characterized the T‐lymphocytes in the skin lesions of 10 patients with cutaneous leishmaniasis and in the nasal lesions of seven patients with mucosal leishmaniasis. with the immunoperoxidase and monoclonal antibody techniques. There was predominance of cells with helper phenotype (Leu 3A + 3B) over suppressor phenotype (Leu 2a) in the lesions of both groups. The helper/suppressor (H/S) ratio in the skin lesions was 1±6 ± 0±5 and in the nasal lesions of mucosal leishmaniasis was 1±7 ± 0±8. The H/S ratios in the peripheral blood of patients with cutaneous leishmaniasis (2±1 ± 0±8) and in patients with mucosal leishmaniasis (1±6 ± 0±8) were comparable and similar to the ratios in the skin and nasal biopsies. The percentage of T‐cells and macrophages expressing the Dr antigen in the cutaneous group (69±5 ± 13±7) was not significantly different from the mucosal patients (90±3 ± 5±7). We conclude that the immunopathology of the skin lesions in cutaneous leishmaniasis is similar to the nasal lesions of mucosal leishmaniasis.

Childhood pneumonia: clinical aspects associated with hospitalization or death

OBJECTIVE To determine which available information at an Emergency Room (ER) consultation is associated with hospitalization or death among children with pneumonia. DESIGN Prospective cohort study. SETTING The ER of one university and one private hospital. MEASUREMENT Using stepwise logistic regression we analyzed factors that showed a univariate association. MAIN RESULTS Of 2,970 cases, the median age was 1.83 years (range 2 days to 14.5 yrs, mean 2.76 +/- 2.72 yrs); 25.8% were hospitalized and 0.8% died. Age (2-11 mos, OR 0.4 [0.2-0.6]; 12-59 mos, OR 0.2 [0.1-0.4]; > or = 5 yrs, OR 0.1 [0.08-0.3]), malnutrition (OR 2.0 [1.4-2.7]), underlying chronic illness (OR 1.4 [1.1-1.8]), tachypnea (OR 1.8 [1.4-2.4]), chest indrawing (OR 1.7 [1.4-2.2]), and somnolence (OR 1.8 [1.4-2.4]) were associated with hospitalization and age (2-11 mos, OR 0.3 [0.08-0.8]; > or = 12 mos, OR 0.06 [0.02-0.2]), malnutrition (OR 3.1 [1.2-7.7]) and underlying chronic illness (OR 4.3 [1.6-11.0]) were associated with death in the multivariate analysis. CONCLUSIONS Several clinical aspects may be used in assessing need for hospitalization (i.e. young age, malnutrition, underlying chronic illness, tachypnea, chest indrawing and somnolence) for children with pneumonia seen at the ER. Individual intrinsic factors such as age, malnutrition and underlying chronic illness were independently associated with death. Pneumonia should be considered a treatable disease and complete recovery can be achieved in the majority of the cases.

The cause of urinary symptoms among Human T Lymphotropic Virus Type I (HLTV-I) infected patients: a cross sectional study.

BackgroundHTLV-I infected patients often complain of urinary symptomatology. Epidemiological studies have suggested that these individuals have a higher prevalence and incidence of urinary tract infection (UTI) than seronegative controls. However, the diagnosis of UTI in these studies relied only on patient information and did not require confirmation by urine culture. The purpose of this study was to investigate the role of urinary tract infection (UTI) as the cause of urinary symptoms in HTLV-I infected patients.MethodsIn this cross sectional study we interviewed, and cultured urine from, 157 HTLV-I seropositive individuals followed regularly at a specialized clinic. All patients were evaluated by a neurologist and classified according to the Expanded Disability Status Scale (EDSS). Urodynamic studies were performed at the discretion of the treating physician.ResultsSixty-four patients complained of at least one active urinary symptom but UTI was confirmed by a positive urine culture in only 12 of these patients (19%); the majority of symptomatic patients (81%) had negative urine cultures. To investigate the mechanism behind the urinary complaints in symptomatic individuals with negative urine cultures, we reviewed the results of urodynamic studies performed in 21 of these patients. Most of them (90.5%) had abnormal findings. The predominant abnormalities were detrusor sphincter hyperreflexia and dyssynergia, findings consistent with HTLV-I-induced neurogenic bladder. On a multivariate logistic regression, an abnormal EDSS score was the strongest predictor of urinary symptomatology (OR 9.87, 95% CI 3.465 to 28.116, P < 0.0001).ConclusionUrinary symptomatology suggestive of UTI is highly prevalent among HTLV-I seropositive individuals but true UTI is responsible for the minority of cases. We posit that the main cause of urinary symptoms in this population is neurogenic bladder. Our data imply that HLTV-I infected patients with urinary symptomatology should not be empirically treated for UTI but rather undergo urine culture; if a UTI is excluded, further investigation with urodynamic studies should be considered.

Clinical effects of intermittent, intravenous cyclophosphamide in severe systemic lupus erythematosus

To evaluate the clinical effectiveness of intermittent intravenous cyclophosphamide in the treatment of severe systemic lupus erythematosus, 20 patients with systemic lupus erythematosus (SLE) and evidence of severe renal involvement or systemic vasculitis, consecutively admitted to the hospital were studied. Cyclophosphamide was administered intravenously at a dosage of 1.0 g/m2 monthly, during 6 months and maintained every 3 months during 12 additional months. Of 10 patients with active lupus nephritis, a reduction or disappearance of proteinuria and maintenance of normal renal function was recorded in 6. Improvement of renal function was observed in 4 out of 7 patients with renal insufficiency at initial evaluation; resolution of renal insufficiency was more frequently observed in patients with recent onset renal failure. At the end of the follow-up (18.0 +/- 14.5 months) disappearance or reduction of nephrotic range proteinuria was recorded in 6 out of 14 patients; there was progression toward renal failure in 4 patients (20%). Response to intravenous cyclophosphamide therapy was observed in 4 of 5 patients with severe extrarenal SLE. Side effects, recorded in 12 patients, were mild and transient and in no patient was the treatment discontinued. Four patients died during the follow-up, although in 2 of them the deaths were not attributable to therapy. Even though this was an open and uncontrolled study, intermittent, intravenous cyclophosphamide was an effective therapy for severe, steroid refractory SLE.