Very early prediction of response to HCV treatment with PEG-IFN-alfa-2a and ribavirin in HIV/HCV-coinfected patients.

The objective of this study was to find very early viral kinetic markers to predict nonresponse to hepatitis C virus (HCV) therapy in a group of human immunodeficiency virus (HIV)/HCV-coinfected patients. Twenty-six patients (15 HCV genotype-1 and 11 genotype-3) were treated with a 48-week regimen of peginterferon-alfa-2a (PEG-IFN) (180 µg/week) and weight-based ribavirin (11 mg/kg/day). Samples were collected at baseline; 4, 8, 12, 18, 24, 30, 36 and 42 h; days 2, 3, 4, 7, 8, 15, 22, 29, 43 and 57 then weekly and monthly. Five patients discontinued treatment. Seven patients (27%) achieved a sustained virological response (SVR). Nadir HCV RNA levels were observed 1.6 ± 0.3 days after initiation of therapy, followed by a 0.3- to 12.9-fold viral rebound until the administration of the second dose of PEG-IFN, which were not associated with SVR or HCV genotype. A viral decline <1.19 log for genotype-1 and <0.97 log for genotype-3, 2 days after starting therapy, had a negative predictive value (NPV) of 100% for SVR. The day 2 virological response had a similar positive predictive value for SVR as a rapid virological response at week 4. In addition, a second-phase viral decline slope (i.e., measured from day 2 to 29) <0.3 log/week had a NPV = 100% for SVR. We conclude that first-phase viral decline at day 2 and second-phase viral decline slope (<0.3 log/week) are excellent predictors of nonresponse. Further studies are needed to validate these viral kinetic parameters as early on-treatment prognosticators of nonresponse in patients with HCV and HIV.

Tissue and serum immune response in chronic hepatitis C with mild histological lesions.

The immunopathogenesis of chronic hepatitis C virus (HCV) infection is a matter of great controversy and has been suggested to involve a complex balance between cytokines with pro and anti-inflammatory activity. We investigated the expression of inflammatory cells and cytokines in the liver and serum of 51 chronically HCV infected patients and compared them to data from two sets of normal controls: 51 healthy blood donors and 33 liver biopsies of healthy liver donors. We also assessed the relationship between selected cytokines and cell populations in hepatic compartments and the disease stage. Compared with controls, hepatitis C patients had a greater expression of portal TNF-alpha, TGF-beta and CD4(+) and acinar IFN-gamma, TNF-alpha, IL-1beta and IL-4, as well as a higher serum concentration of IL-2, IL-10 and TGF-beta. Significant positive correlations were found between portal CD4+ and TNF-alpha, portal CD8(+) and TGF-beta, portal CD45(+)RO and TNF-alpha, acinar CD45(+)RO and IFN-gamma and acinar CD57(+) and TGF-beta. In conclusion, we have shown that (i) in this sample of predominantly mild disease, the immune response was associated with a pro-inflammatory response pattern, (ii) CD4(+) T-lymphocytes played a major role in orchestrating the immune response and (iii) these events primarily took place in the portal space.

Factors associated with mortality in patients with bloodstream infection and pneumonia due to Stenotrophomonas maltophilia.

Severe infections caused by Stenotrophomonas maltophilia are associated with high mortality, and strategies to improve the clinical outcome for infected patients are needed. A retrospective cohort study of patients with bloodstream infection (BSIs) and pneumonia caused by S. maltophilia was conducted. Multivariate analysis was performed to access factors associated with 14-day mortality. A total of 60 infections were identified. Among these, eight (13%) were pneumonias and 52 were BSIs; 33.3% were primary, 13% were central venous catheter (CVC)-related and 40% were secondary BSIs. Fifty-seven (85%) patients had received previous antimicrobial therapy; 88% had CVC, 57% mechanical ventilation and 75% were in the intensive care unit at the onset of infection. Malignancy (45%) was the most frequent underlying disease. The mean of the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores was 17 and for the Sepsis-related Organ Failure Assessment (SOFA) score, it was 7 points. The overall and 14-day mortality were, respectively, 75% and 48%. Forty-seven (78%) patients were treated and, of these, 74% received trimethoprim-sulfamethoxazole. Independent risk factors associated with mortality were SOFA index >6 points (0.005) and septic shock (0.03). The Kaplan-Meier estimations curves showed that patients with APACHE II score >20 and SOFA score >10 had a survival chance of, respectively, less than 8% and less than 10% (P

Genotypic distribution of hepatitis C among hepatitis C and HIV co-infected patients in Brazil.

Information on hepatitis C virus (HCV) genotypic distribution among HIV-HCV co-infected patients is lacking in Brazil as well as other Latin American countries. The objective of this study was to evaluate the level of exposure to different risk factors associated with HCV transmission among a group of co-infected patients and to characterize the genotypic distribution of HCV in this cluster. A series of 100 HIV-HCV co-infected patients was analysed. The data to be analysed were collected from specific laboratory tests. Information was collected through a questionnaire. HCV genotyping was carried out by sequencing the 5' non-coding region of HCV. Chi-square and Fischer association tests or Kruskal-Wallis test were used to study the association between HCV transmission-related variables and the established genotypes. In conclusion, exposure to multiple risk factors associated with HCV transmission was common among HIV co-infected patients and an association between HCV genotype 3 and intravenous drug user was observed.

Investigation of the possible association between nosocomial candiduria and candidaemia.

This study aimed to determine whether candiduria is associated with the occurrence of nosocomial candidaemia. In the case-control part of the study, 115 cases (nosocomial candidaemia) and 115 controls (nosocomial bacteraemia) were similar in age, severity of condition and time of hospitalisation. There was a significant association of candidaemia with candiduria (OR 9.79; 95% CI 2.14-44.76). In the microbiology part of the study, 23 pairs of Candida-positive urine and blood cultures were obtained from 23 patients. In ten (43%) cases, the urine and blood culture isolates belonged to different species, and molecular typing showed a difference in two of the 13 cases yielding the same species from both specimens. Overall, there was a significant association between candiduria and candidaemia, but the Candida isolates from urine and blood were different for 52% of the patients. Thus, the data indicated that the urinary tract was probably not a source for the candidaemia.

Clinical classification of tetanus patients.

The authors propose a clinical classification to monitor the evolution of tetanus patients, ranging from grade I to IV according to severity. It was applied on admission and repeated on alternate days up to the 10th day to patients aged > or = 12 years admitted to the State University Hospital, Recife, Brazil. Patients were also classified upon admission according to three prognostic indicators to determine if the proposed classification is in agreement with the traditionally used indicators. Upon admission, the distribution of the 64 patients among the different levels of the proposed classification was similar for the groups of better and worse prognosis according to the three indicators (P > 0.05), most of the patients belonging to grades I and II of the proposed classification. In the later reclassifications, severe forms of tetanus (grades III and IV) were more frequent in the categories of worse prognosis and these differences were statistically significant. There was a reduction in the proportion of mild forms (grades I and II) of tetanus with time for the categories of worse prognostic indicators (chi-square for trend: P = 0.00006, 0.03, and 0.00000) whereas no such trend was observed for the categories of better prognosis (grades I and II). This serially used classification reflected the prognosis of the traditional indicators and permitted the comparison of the dynamics of the disease in different groups. Thus, it becomes a useful tool for monitoring patients by determining clinical category changes with time, and for assessing responses to different therapeutic measures.

Candida parapsilosis fungemia associated with implantable and semi-implantable central venous catheters and the hands of healthcare workers.

A cluster of six cases of fungemia among hematology, bone marrow transplant, and oncology patients was investigated in a case-control study (18 controls). The use of implantable and semi-implantable central venous catheters was significantly associated with cases (p = 0.016). The hands of three healthcare workers (HCWs) were positive for Candida parapsilosis. Electrophoretic karyotyping showed two profiles among patients and HCWs, and five among six unrelated strains. The profiles of two HCWs matched the ones of the patients they had handled. The patients' strains were moderate or strong slime producers, whereas none of the HCWs' were strong producers. In conclusion, our results indicated the occurrence of an outbreak C. parapsilosis fungemia related to long-term central venous catheters in which the hands of HCWs were implicated. The amount of slime production might be associated with the pathogenicity of the strains.

Outer-membrane proteins pattern and detection of beta-lactamases in clinical isolates of imipenem-resistant Acinetobacter baumannii from Brazil.

In order to compare imipenem-sensitive and -resistant Acinetobacter baumannii strains isolated from three patients, ribotyping, plasmid, beta-lactamase detection and outer-membrane analysis were performed. Ribotyping and the use of a beta-lactam during the period when the strains were isolated suggested that they had a common origin and that resistance occurred in vivo. Outer membrane analysis showed no difference between susceptible and resistant strains with the exception of an A2 imipenem-resistant strain that lost a protein band of 31-36 kDa. Beta-lactamases were detected using isoelectric focusing in all strains (pI of 7.4). In addition, two beta-lactamases (pI of 5.9 and 6.7) were found in imipenem-resistant isolates. The double-disc technique demonstrated the presence of a beta-lactamase capable of imipenem inactivation in resistant strains. Plasmid analysis showed that all susceptible strains had the same pattern, one resistant strain did not have any plasmid, one had the same plasmid pattern of its susceptible pair and only one had a different pattern when compared with its susceptible pair.

An outbreak of nosocomial Legionnaires' disease in a renal transplant unit in São Paulo, Brazil. Legionellosis Study Team.

From June 1989 to March 1990 there were eight cases of Legionnaires' disease caused by Legionella pneumophila serogroup 1 in a renal transplant unit. There were seven cases of pneumonia and one case of pleural effusion. A study was conducted to identify the source of the outbreak. Legionella anisa was cultured from tap water. Twenty-seven staff members of the unit were serologically tested and antibody titres were positive in two. The probable source of infection was the potable water system. Control measures were hyperchlorination and heating of the water, after which there were no further cases during 5 months' follow up. We believe this is the first reported Legionnaires' disease outbreak in Latin America.

Factors associated with penicillin-nonsusceptible pneumococcal infections in Brazil.

Resistance of Streptococcus pneumoniae is a worldwide, growing problem. Studies of factors associated with resistance to penicillin have not been conducted in Brazil. The objective of the present study was to evaluate factors associated with infection by S. pneumoniae not susceptible to penicillin. A prevalence study was conducted including all patients with a positive culture for S. pneumoniae in a hospital from July 1991 to December 1992 and the year 1994. Of 165 patients identified, 139 were considered to have clinically relevant infections and 88% of them had invasive infections. All infections were community acquired and consisted of pneumonia (44%) and of central nervous system (19%), pelvic or abdominal (12%), upper airway or ocular (12%), primary bloodstream (9%) and skin and soft tissue (5%) infections. Mortality was 25%. Susceptibility to penicillin was present in 77.6% of the isolates; 21.8% were relatively resistant, and one isolate was resistant (minimal inhibitory concentration = 4 micro g/ml). Multivariate analysis showed that age below 4 years (odds ratio (OR): 3.53, 95% confidence interval (95%CI): 1.39-8.96) and renal failure (OR: 5.50, 95%CI: 1.07-28.36) were associated with lack of susceptibility to penicillin. Bacteremia occurred significantly less frequently in penicillin-nonsusceptible infections (OR: 0.34, 95%CI: 0.14-0.84), possibly suggesting that lack of penicillin susceptibility is associated with lower virulence in S. pneumoniae.

Treatment of nosocomial pneumonia: an experience with meropenem.

This study aimed at evaluating the efficacy and safety of meropenem as first choice treatment for nosocomial pneumonia (NP) in intensive care units (ICU) in Hospital das Clínicas (HC) - University of São Paulo; a hospital with high incidence of antimicrobial resistance. Prospective, open, and non-comparative trial with meropenem were done in patients with ventilator-associated or aspiration NP in 2 ICUs at HC - University of São Paulo. Etiologic investigation was done through bronchoalveolar lavage and blood cultures prior to study entry. Twenty-five (25) critically ill patients with NP were enrolled (mean age 40 years). Ventilator-acquired pneumonia was responsible for 76% of cases and aspiration NP for 24%. Specific etiologic agents were identified and considered to be clinically and temporally responsible for NP in 11 (44%) patients. A. baumanii was responsible for 6 cases (55%), P. aeruginosa for 3 (27%), and S. aureus for 2 (18%). At completion of treatment, 19 patients (76%) showed either cure (48%) or improvement (28%) after use of meropenem therapy. Mortality was 12% at the end of therapy (8% after excluding 1 non-evaluable patient). After 4 to 6 weeks of follow-up, 12 (48%) patients had improved or been totally cured, and overall mortality was 24%. Clinical complications were observed in 11 patients (44%), with none of them definitely related to the study drug. Meropenem as monotherapy was effective and well-tolerated in most NP patients in our ICU. The low mortality rate in this study might have been due to first choice use of this drug. Controlled, drug comparative clinical trials are needed to support this preliminary observation.

Fulminant hepatitis: a clinical review of 11 years.

24 cases of fulminant hepatitis (FH) hospitalized in the Clínica de Doenças Infecciosas e Parasitárias do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo during the period from January 1976 to December 1986 were reviewed from their clinical, epidemiological and laboratorial aspects. 88% of the patients died; 20 patients (83%) presented hemorrhages and, of these, 19 died. Bacterial infections occurred in 14 patients (58%) all of whom died. Ascitis was noted in 3 cases; cerebral edema was present in 16 cases. Maximal ALT levels for each patient during hospitalization ranged widely from 81 to 4,460 UI/l. Thirteen patients presented high creatinine levels (54%). Prothrombin time activity ranged from 2.1% to 67%. Fever was present in 20 cases (83%). Encephalopathy occurred within the first 2 weeks of illness in 72% of the cases. In 7 cases other illnesses were present. The etiology could not be determined in 13 cases. In 3 cases it was due to yellow fever and 6 cases were caused by viruses other than yellow fever. In one case the cause was drug usage and in another case, possibly alcohol. The authors believe that the clinical definition of FH requires further discussion before it is established. In this study FH is a young person's disease. The mortality found was similar to that by other authors. Factors that contributed to death were: hemorrhages and bacterial infection. Factors that worsened the prognosis of hepatitis were: associated illnesses and surgical procedure. The levels of ALT during hospitalization did not correlate well with the severity of the hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatitis C virus seroprevalence and risk factors among patients with HIV infection.

The objective of this study was to evaluate the prevalence and risk factors associated with HCV infection in a group of HIV seropositive patients. We analyzed the medical records of 1,457 patients. All patients were tested for HCV infection by third generation ELISA. Whenever possible, a sample of the positive patients was also tested for HCV by PCR. HCV positive patients were analyzed according to their risk factors for both infections. The prevalence of anti-HCV positive patients was 17.7% (258 patients). Eighty-two (82) of these patients were also tested by PCR and 81 were positive for HCV virus (98%). One hundred fifty-one (58.5%) were intravenous drug users (IDU); 42 (16.3%) were sexual partners of HIV patients; 23 (8.9%) were homosexual males; 12 (4.7%) had received blood transfusion; 61 (17.5%) had promiscuous sexual habits; 14 (5.4%) denied any risk factor; 12 (4.7%) were sexual partners of IDU. Two hundred four patients mentioned only one risk factor. Among them, 28 (10.9%) were sexual partners of HIV-positive patients. Although intravenous drug use was the most important risk factor for co-infection, sexual transmission seemed to contribute to the high HCV seroprevalence in this group of patients.

Resistance of streptococcus pneumoniae to antimicrobials in São Paulo, Brazil: clinical features and serotypes.

To study resistance to antimicrobials, serotypes and clinical features of S. pneumoniae in S. Paulo, Brazil, 50 patients with a positive culture were evaluated: 7 were considered carriers and 43 had pneumococcal infections. Pneumonia and meningitis were the most common infections. Mortality was 34% and underlying diseases were present in 70%. Relative resistance to penicillin occurred in 24% and complete resistance was not detected. Resistance to tetracycline was 32% and to sulfamethoxazole/trimethoprim 32%; one strain had intermediate susceptibility to erythromycin; no resistance was present for chloramphenicol, rifampin or vancomycin. Resistance to at least one of the drugs tested occurred in 62%. Results by the E-test for penicillin were similar to those by the agar dilution method. There were 24 different serotypes and 74% of the strains belonged to the 23-valent vaccine including all the penicillin-resistant strains. In this study S. pneumoniae caused severe infections and presented a high resistance rate to commonly used antimicrobials. Routine surveillance of resistance and the use of vaccination, as well as the restriction of inappropriate use of antimicrobials, are recommended in São Paulo, Brazil.

Prevalence of hepatitis B and C in the sera of patients with HIV infection in São Paulo, Brazil.

The objective of this study was to evaluate the prevalence of hepatitis B and C viruses in a group of HIV infected patients, followed at a single institution since 1996. 1,693 HIV positive patients (1,162 male, 531 female) were tested for HBV infection. Virological markers for HBV included HBsAg and total anti-HBc by ELISA. 1,457 patients (1,009 male, 448 female) were tested for HCV infection. Detection of HCV antibodies was carried out by ELISA. A sample of HCV antibody positive patients was tested for HCV by PCR to confirm infection. Of 1,693 patients tested for HBV, 654 (38.6%) and 96 (5.7%) were anti-HBc and HBsAg positive, respectively. Of 1, 457 patients tested for HCV, 258 (17.7%) were anti-HCV positive. 82 of these patients were also tested by PCR and 81 were positive (98%). Of 1,411 patients tested for HBV and HCV 26 (1.8%) were positive for both viruses.

Sexual transmission of hepatitis C virus.

In order to contribute to a better understanding of the forms of acquisition of hepatitis C virus (HCV) in Brazil, with special emphasis on sexual transmission, we determined the presence of HCV infection in regular partners and in non-sexual home communicants of blood donors seen at Fundação Pró-Sangue Hemocentro de São Paulo from January 1992 to July 1996. Of 154 blood donors with HCV infection (index cases), 111 had had regular partners for at least 6 months. Sixty-eight of 111 partners were evaluated for HCV infection. Of these, 8 (11.76%) were considered to have current or previous HCV infection; a history of sexually transmissible diseases and index cases with a positive HCV-RNA test were more prevalent among partners with HCV infection. Of the 68 index cases whose partners were studied, 56 had non-sexual home communicants. Of the total of 81 home communicants, 66 accepted to be evaluated for HCV infection. None of them was HCV-positive, suggesting that the high prevalence of HCV infection among partners may be attributed at least partially to sexual transmission.

Five cases of nosocomial and community-acquired Legionnaires' disease in São Paulo, Brazil.

Legionella sp has been emerging over the last decade as an important cause of pneumonia both hospital and community-acquired. Following an outbreak in a Renal-Transplant Unit stocked serum was tested for antibodies against Legionella pneumophila serogroup 1, and 5 cases of Legionnaires' Disease were reviewed. Two of the cases were nosocomial and three cases were community-acquired. Clinical and laboratorial aspects were similar to those expected for other causes of pneumonia, however jaundice was encountered in two cases. This study suggests that the real incidence of pneumonia caused by Legionella sp is being underestimated and the authors emphasize the importance of considering Legionnaires' Disease when empirically treating community-acquired pneumonia.

Aerosolised pentamidine for Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome.

The goal of this study was to evaluate inhaled pentamidine for the treatment of patients with mild and moderate Pneumocystis carinii pneumonitis. Eight adults with AIDS and pneumocystis pneumonia (4 with a first episode and 4 with a repeat pneumocystosis) received daily inhalations of aerosol pentamidine isethionate for 21 days. Six patients were treated with doses of 300 mg of pentamidine and the remaining 2 received 600 mg every day. In the 300 mg treatment group, 2 individuals showed discrete and transient neutropenia. However, both subjects that received 600 mg of aerosol pentamidine daily developed leukopenia. One of them had major toxicity (overall severe intolerance of 12.5%) that required drug discontinuation and did not allow any analysis of the treatment efficacy. Of the 7 evaluable patients, 6 (88%) completed the treatment successfully. One subject of the 300 mg regimen experienced an early recurrence. In conclusion, inhaled pentamidine is an effective treatment for mild and moderate cases of P. carinii pneumonia. It is less toxic than standard anti-pneumocystis therapy and is suitable for outpatient use.

Possible oral transmission of acute Chagas' disease in Brazil.

In October 1986, 7 to 22 days after a meeting at a farm in Paraíba state, 26 individuals presented with a febrile illness associated with bilateral eyelid and lower limb edema, mild hepatosplenomegaly, lymphadenopathy and, occasionally a skin rash. A 11-year-old boy exhibited atrial premature complexes and a 74-year-old patient developed acute heart failure. In two patients hospitalized in São Paulo city, acute Chagas' disease was diagnosed by the demonstration of circulating Trypanosoma cruzi. At autopsy in a fatal case, acute Chagas' cardiomyopathy was demonstrated. Xenodiagnosis were positive in 9 out of 14 tested patients. A specific IgG immune response was found in all patients and specific IgM antibodies were identified in 20 out of 22 tested patients. A epidemiological survey showed the existence of Triatoma brasiliensis in the outbuildings of this farm, but none in the house where most of the guests stayed. A high rate of infection with Trypanosoma cruzi was found in opossums. These observations together with those related to the food consumed by the patients, lead the authors to suggest that the human infections resulted from oral contamination probably originating from naturally infected marsupials in the area or crushed infected bugs.

[Acute Chagas' disease: transmission routes, clinical aspects and response to specific therapy in diagnosed cases in an urban center]. / Doença de Chagas aguda: vias de transmissão, aspectos clínicos e resposta à terapêutica específica em casos diagnosticados em um centro urbano.

The authors report clinical features and therapeutic response of 24 outpatients with acute Chagas' disease, and 3 in the initial chronic phase, referred to the Clinic for Infectious and Parasitic Diseases of the FMUSP "Clínicas" Hospital between 1974 and 1987. The following transmission routes were involved: triatominae in 7 cases, blood transfusion in 9, kidney transplantation and/or blood transfusion in 4, accidental in 1, oral route in 3, probably breast feeding in 1, congenital or breast feeding in 1, and congenital or blood transfusion in 1. Six patients infected by triatominac acquired the disease between 1974 and 1980 and one in 1987. The blood transfusion infected patients acquired the disease in Greater São Paulo, seven of whom after 1983. The acute phase Chagas' disease was oligosymptomatic in 4 patients: three of such patients being immunocompromised by drugs or other diseases. Another two adult immunocompromised patients developed myocarditis and congestive heart failure. Clinical features were severe in 5 from 6 children under two years, irrespective of the transmission route. Evaluation of the acute phase patients treated with benznidazol (4-10 mg/kg/day) showed: therapeutic failure in 4/16 (25.0%); possible cure in 9/16 (53.2%) and inconclusive results in 3/16 (18.8%). The antibody and complement-mediated lysis reaction was in keeping with the xenodiagnosis in 18/22 cases, having shown negative results after treatment earlier than classical serological reactions. One aplastic anaemia patient receiving corticosteroid presented lymphoproliferative disease 6 years after being treated with benznidazol for acute Chagas' disease.