Bacterial meningitis in an urban area: etiologic study and prognostic factors.

OBJECTIVES: The study of clinical features, diagnostic methods and prognostic factors of bacterial meningitis, in an urban area. PATIENTS AND METHODS: All patients admitted between June 2001 and July 2004 in the emergency departments of a few hospitals, with the diagnosis of bacterial meningitis were included. CSF and blood cultures were performed in every case. Phenotypic characterization of strains of Streptococcus pneumoniae and Neisseria meningitidis identified by culture were performed. In order to detect the three most common agents it was done a PCR assay in culture negative CSF samples. RESULTS: Bacterial meningitis was diagnosed in 201 patients. Etiologic definition was based on culture in 142 patients (70.6%), done by CSF PCR assay in 33 (16.4%) other patients and exclusively by latex agglutination test results in two cases. Thus, an etiologic diagnosis was established in 177 (88%) cases. Antigenic characterization showed a slight prevalence of N. meningitidis phenotype C:2b:P1; the S. pneumoniae serotype characterization showed that 43.8% of identified serotypes are not included in any of the available vaccines. Eighteen patients died (8.9%). The statistic analysis found that factors associated with an adverse outcome were age older than 50 years (OR 7.07; IC 95% 1.1-27.4), the presence of comorbidities (OR 3.3; IC 95% 1.1-9.6) and the occurrence of systemic complications (OR 5.8; IC 95% 2.1-16.0). CONCLUSIONS: This epidemiologic pattern is similar to that found in other countries after the introduction of Haemophilus influenzae b conjugated vaccine. The association of culture and noncultural methods of diagnosis had a better performance in defining the etiology. Comparing to other series, in-patients mortality rate was lower (8.9%) than usually referred to, being considered unfavourable prognostic factors the age more than 50 years, the presence of comorbidities and of systemic complications.

Toscana virus meningitis in Portugal, 2002-2005.

Toscana virus infection is endemic in Italy, but has also been documented in other Mediterranean countries. Our aim was to investigate the occurrence of Toscana virus (TOSV) meningitis in children and young adults in a metropolitan area in the north of Portugal. Cerebrospinal fluid samples from 308 patients with the diagnosis of meningitis and with negative bacterial culture were tested for enteroviruses and herpesviruseses by reverse transcription PCR. Those samples that proved negative for enterovirus and herpesvirus were tested for Toscana virus with a commercial reverse transcription nested PCR assay. In total, we investigated 106 samples, collected between May and September during the four-year period between 2002 and 2005 from patients younger than 30 years old. Toscana virus was the cause of meningitis in six (5.6%) of the cases, three children and three young adults. All had a benign course and self-limited disease. Since a first case report of TOSV infection 1985 and another in 1996, both in foreign tourists, these six cases of Toscana virus meningitis are, to our knowledge, the first diagnosed in Portuguese inhabitants, and they underline the need for more studies on the prevalence of this virus in Portugal.

AIDS does not alter the total number of neurons in the hippocampal formation but induces cell atrophy: a stereological study.

Although cognitive dysfunction is a common finding in patients with acquired immunodeficiency syndrome (AIDS) its pathogenesis remains controversial. Given the involvement of the hippocampal formation in the processing of cognitive information and the scarcity of quantitative studies in this brain region, we have examined, using stereological methods, the hippocampal formations of AIDS patients. The study was performed in ten AIDS patients and ten age-matched controls. All cases were male. The Principle of Cavalieri was applied to estimate the volume of the layers of the dentate gyrus and of the CA3 and CA1 hippocampal fields. The fractionator and the nucleator were used as estimators of the total number, and mean somatic and nuclear volumes of the neurons in the cell-containing layers of all hippocampal subdivisions. No cell death was detected in AIDS patients but the global volume of their hippocampal formations was significantly decreased due to the reduced volume of its layers, mainly the cell-containing layers. Furthermore, the somatic and nuclear volumes of the neurons in the hippocampal formation were significantly decreased in AIDS patients. No correlation was found between the estimates obtained and the presence or absence of neurological involvement. Our results show that neurons in the hippocampal formation of AIDS patients display marked morphological changes, despite the maintenance of their total number. These alterations are likely to lead to dysfunction of the hippocampal circuitries and, thus, might contribute to explaining the dementia features which occur in this condition.

Pericardial involvement in human immunodeficiency virus infection.

STUDY OBJECTIVES: Previous studies have showed that the pericardium is frequently involved in HIV infection. However, the characteristics and etiology of the pericardial abnormalities that have been found remained poorly defined. We analyzed the features of pericardial involvement in these patients and investigated the clinical variables associated with moderate and severe effusions. DESIGN: Prospective, clinical, and echocardiographic study. SETTING: The service of infectious diseases of a university hospital. PATIENTS: 181 consecutive patients at all stages of HIV infection. RESULTS: Only one patient (0.55%) had acute pericarditis. Seventy-five patients (41%) had an asymptomatic pericardial effusion; in 23 patients (13% of all patients), the effusion was either moderate or severe. Ten cases (5.5% of all patients) of moderate or severe effusions resulted in right atrium diastolic compression, and three of these cases (1.6% of all patients) required pericardiocentesis for the management of tamponade. Six patients (3%) presented with echogenic pericardial masses of undetermined etiology. A moderate or severe effusion was present in a greater number of patients with symptomatic HIV infection than was present in asymptomatic HIV-infected patients, respectively: 17 vs 2% (p = 0.015). The following are variables independently associated with moderate or severe pericardial effusions: heart failure (odds ratio, 20.3; p = 0.0001); Kaposi's sarcoma (odds ratio, 8.6; p = 0.01), tuberculosis (TB; odds ratio, 47.2; p = 0.0006); and other pulmonary infections (odds ratio,15.0; p = 0.02). CONCLUSIONS: Most of these moderate or severe effusions are clinically unsuspected, but they can lead to life-threatening tamponade. This fact seems to justify echocardiographic surveillance in HIV-infected patients, especially in those with heart failure, Kaposi's sarcoma, TB, or other pulmonary infections.

[Etiologic diagnosis of viral meningitis. Study of 142 cases]. / Diagnóstico etiológico da meningite vírica. Estudo de 142 casos.

Viral meningitis is a common disease, most often benign and striking predominantly children. In 1997, there was an outbreak of viral meningitis in the North of Portugal and this pathology accounted for 496 admissions to the Infectious Diseases Department of S. João Hospital. The authors' aim was to determine the etiology of the cases of viral meningitis admitted to the S. João Hospital by, in a first phase, searching enterovirus and serology for mumps in a sample of 142 patients with symptoms, signs and cerebrospinal fluid (CSF) cytochemical abnormalities typical of viral meningitis, in the absence of any bacterial or fungal growth (in blood and/or CSF) and with negative soluble bacterial antigens in CSF. The enterovirus was detected by polymerase chain reaction (PCR) and, in a small number of cases, by shell vial culture. The diagnosis of mumps was made by the detection of specific IgM antibodies in serum, using an enzyme-linked immunosorbent assay. The diagnosis was reached in 70 patients (49.3%): 47 (33.1%) had mumps meningitis and 23 (16.2%) enterovirus infection (PCR positive in all; culture positive in only 2 cases). In 72 patients (50.7%), the agent was not identified. Although only two agents were searched for, the diagnosis was made in a high proportion of cases. The culture method used for the isolation of enterovirus was found to have a low sensitivity.

[Kaposi sarcoma associated with HIV infection]. / Sarcoma de Kaposi associado a infecção pelo VIH.

Kaposi's sarcoma is the most common neoplasm in AIDS patients. In a 12-year period, 45 (8%) cases were diagnosed in 552 patients with AIDS. Epidemiological and clinical aspects are reviewed. The disease occurred predominantly in males and homosexuals. In 30 (67%) patients it was the first manifestation of AIDS. Skin and/or oral disease was the most frequent manifestation observed in our patients; 13 (29%) had visceral involvement. Previous or concommitant opportunistic diseases, systemic illness and severe immunosuppression were present in the majority of the patients. Opportunistic infections were the cause of death in 30 patients; in five others, Kaposi's sarcoma was responsible for death. Advances in antiretroviral therapy were of benefit for patients submitted to chemotherapy and may contribute to a reduction in morbidity with this neoplasm.

Predictors of myocardial dysfunction in human immunodeficiency virus-infected patients.

BACKGROUND: Some of the most frequent manifestations of heart involvement in human immunodeficiency virus (HIV) infection include right and left ventricular dysfunction. The pathogenesis remains obscure. METHODS AND RESULTS: This prospective clinical and echocardiographic study involved 181 patients at all stages of HIV infection. We tested a set of clinical variables using a backward logistic regression model to assess their ability to independently predict the presence of ventricular dysfunction. The presence of pulmonary infections (all etiologies mixed) was the only variable independently associated with isolated right ventricular dysfunction (odds ratio = 4.08; P = .02). Signs suggestive of pulmonary arterial hypertension were present in 71% of the patients with right ventricular dilation. History of previous opportunistic infections (all etiologies mixed) (odds ratio = 10.9; P = .0026) and time since the diagnosis of acquired immunodeficiency syndrome more than 12 months (odds ratio = 6.6; P = .03) were the only two independent predictors of left ventricular dysfunction. CONCLUSIONS: Isolated right ventricular dysfunction may be secondary to pulmonary hypertension caused by repetitive pulmonary infections and not to primary myocardial disease. The aggressive treatment of opportunistic infections may become an important element of heart failure prophylaxis in HIV infection because they may be associated with left ventricular dysfunction.

Left ventricular dysfunction in human immunodeficiency virus (HIV)-infected patients.

We evaluated left ventricular function by echocardiography in a prospective study that included 98 consecutive human immunodeficiency virus (HIV)-infected patients and 40 HIV-seronegative normal controls. When compared with controls, HIV patients showed increased isovolumic relaxation time (101+/-18 ms versus 71+/-10 ms; p<0.0001) and left ventricular diastolic diameters (51+/-6 mm versus 47+/-3 mm; p<0.0005), and decreased fractional shortening (31+/-6% versus 37+/-2%; p<0.0001). Diastolic dysfunction was the most frequent finding (63% of the patients). We found depressed ejection fraction in 31 (32%) patients. Only 8 (8%) patients had symptomatic congestive heart failure. Left ventricular dysfunction was not attributable to intravenous drug abuse or to therapy. It was less severe in earlier stages of the infection (fractional shortening: acquired immunodeficiency syndrome=30%+/-6%, asymptomatic HIV-seropositives 34%+/-5%; p<0.005) and in HIV-2-infected patients. Patients with opportunistic infections (all aetiologies mixed) had more frequent congestive heart failure than those without infections (16% of the patients with versus 4% of the patients without infections; p<0.05). The fact that even asymptomatic HIV-seropositives had signs of left ventricular dysfunction (fractional shortening: asymptomatic HIV-seropositives=34%+/-5%; controls=37%+/-2%; p<0.05) favours the hypothesis of the HIV being one of the causes of these abnormalities.

Inhalatory pentamidine therapy and the duration of the QT interval in HIV-infected patients.

We evaluated the effect of chronic Pneumocystis carinii pneumonia (PCP) prophylaxis, with a once a month dose of 300 mg of inhalatory pentamidine isethionate, on QT interval duration. We included 22 human immunodeficiency virus (HIV)-infected patients: 11 were on this medication and 11 were not. The two groups were matched for age, sex and HIV infection stage. No patient had any clinical condition or was under any medication known to affect the duration of the QT interval. The heart rate-corrected QT (QTc) was obtained by averaging the observations of three independent observers. QTc duration was similar in both groups. The time separating pentamidine administration and the performance of the ECG did not influence the results, neither did the duration of inhalatory pentamidine therapy. Our results suggest that inhalatory pentamidine does not prolong the QT interval duration and so, as opposed to what has been reported concerning intravenous pentamidine therapy, does not seem to induce an increased risk of torsades de pointes.

Zidovudine therapy and left ventricular function and mass in human immunodeficiency virus-infected patients.

Human immunodeficiency virus-infected (HIV) patients frequently present left ventricular dysfunction. Its etiology is not elucidated but zidovudine has been postulated as a possible cause factor. This study is an attempt to clarify this issue by evaluating the effect of zidovudine therapy on left ventricular function in these patients. We prospectively studied by echocardiographic examination 11 consecutive HIV-infected patients who were assigned for zidovudine therapy. We excluded patients that had a history or a physical examination suggestive of ischemic, rheumatic, congenital, or hypertensive heart disease. Patients with diabetes mellitus, excessive ethanol intake and patients on potentially cardiodepressant drugs were also excluded. Echocardiographic examination was performed immediately before the initiation of zidovudine therapy and 1 and 3 months later. Left ventricular diameters, mass and fractional shortening showed no significant difference from baseline, at 1 or 3 months after the initiation of zidovudine therapy. Our results suggest that zidovudine therapy has no effect on left ventricular diameters, mass or fractional shortening during a short term.

HIV-2 infection with a long asymptomatic period.

We give details of a patient infected with HIV-2 which had what we believe to be the longest asymptomatic period so far reported. The infection was probably acquired though a blood transfusion in Africa 27 years ago. At present the patient remains asymptomatic and her cellular defence mechanisms, evaluated by CD+4 lymphocyte counts and hypersensitivity skin tests, are not severely compromised. HIV-2 has come distinct epidemiological, clinical and biological features which are different from the related HIV-1 and deserve investigation in order for its natural history to be better understood.

Update on the use of cefotaxime for pediatric meningitis in Portugal.

We treated 256 children who had identified bacterial meningitis with cefotaxime. Causative organisms were: Neisseria meningitidis in 108 cases, Streptococcus pneumoniae in 61, Haemophilus influenzae in 60, enteric Gram-negative bacilli in 21, and Staphylococcus spp. in six. Daily doses of cefotaxime were 150-200 mg/kg. A total of 240 patients (93.7%) were cured. In the cured patients, sterilization of cerebrospinal fluid was obtained in the first 72 h of treatment in 214 (80.0%). Cefotaxime is an effective and safe drug for the treatment of childhood bacterial meningitis.

Dysrhythmic profile of human immunodeficiency virus infected patients.

We prospectively studied, with 24-h Holter monitoring, 21 consecutive human immunodeficiency virus (HIV) infected patients, at all stages of the infection, in order to assess their dysrhythmic profile. Three (14.3%) patients presented one isolated run of supraventricular tachycardia, with < 10 beats, that was considered clinically irrelevant. No patient presented other clinically relevant supraventricular or ventricular tachy or bradydysrhythmias. One (4.8%) patient presented intermittent Mobitz type I second-degree AV block, two (9.5%) patients paroxistic 2:1 AV block and one (4.8%) patient presented a bifascicular block on the 12-lead ECG that persisted during the ambulatory recording. This study suggests that clinically relevant cardiac tachydysrhythmias are rare in our population of HIV infected patients. On the other hand we found an unexpectedly high incidence of cardiac impulse conduction disturbances.

Salmonella typhi meningitis.

Whereas typhoid fever is still an endemic disease in some parts of the world, meningeal involvement in this disease is a rare occurrence. We report a case of Salmonella typhi meningitis in a 70-year-old woman. The patient was treated with ampicillin and the only sequela was right-sided deafness.

Treatment of childhood bacterial meningitis.

One hundred and eighty-seven children with identified bacterial meningitis were treated with intravenous cefotaxime: 15 patients were neonates, 79 infants, and 93 were aged from 1 to 14 years. Causative organisms were: Neisseria meningitidis in 80 cases, Streptococcus pneumoniae in 41, Haemophilus influenzae in 40, enteric gram-negative bacilli in 20 and Staphylococcus spp. in six. Enteric gram-negative bacilli included: Salmonella spp. in 14 cases, Klebsiella pneumoniae in two, and Escherichia coli, Enterobacter sakazakii and Acinobacter calcoaceticus in one each; in one case the organism was not specified. Daily dose of cefotaxime was 150 to 300 mg/kg. Concomitant treatment with an aminoglycoside was used in seven cases. One hundred and seventy-two patients (92.0%) were cured. Fever persisted for a mean of five days and meningeal signs for a mean of four days. Fifteen (8.0%) patients died: most [13] of them were admitted in coma, and two in shock. Death occurred in the first 48 h in ten cases. Sterilization of CSF was achieved in the first 72 h of treatment in 155 (90.1%) of the cured patients. Cefotaxime was well tolerated. CSF penetration of cefotaxime was evaluated in seven patients: concentrations ranged from 0.499 mg/l to 2.829 mg/l. Based on this clinical study, cefotaxime is an effective and safe drug for the treatment of childhood bacterial meningitis.

Use of a latex agglutination test in rapid diagnosis of acute meningitis.

Capsular antigens of Neisseria meningitidis groups A, B, C, Y and W135, Streptococcus pneumoniae and Haemophilus influenzae were searched in CSF specimens of 66 patients with acute meningitis, using a latex agglutination test. Simultaneously CSF samples were processed for Gram stain and culture. Blood cultures were also performed in all patients. The test was positive in 43 (82.7%) samples: N. meningitidis-19, S. pneumoniae-18 and H. influenzae-6. In 32 samples the result of the test was concordant with CSF or blood culture. In 11 cases the test was positive but CSF or blood cultures were negative. Gram stain was diagnostic in 13 (25%) samples in which the latex agglutination test was also positive, and were negative in the remaining cases. There were six false negative tests. In 17 cases the test, culture and Gram stain were simultaneously negative: 14 cases corresponded to viral meningitis, and the three other were unidentified purulent meningitis. Concluding, the test was useful in early aetiologic diagnosis of acute meningitis, but the occurrence of false negative results requires a complete bacteriological study.

Human leptospirosis--a review of 50 cases.

Epidemiological and clinical aspects of 50 consecutive patients, 47 adults and three children, hospitalized between 1977 and 1987 for human leptospirosis, were reviewed. 45 (90%) of the patients were from rural regions. 32 (64%) cases occurred in individuals at occupational risk for the infection. 35 (70%) cases were registered in the warm season. The source of infection was known in 34 (68%) cases. Weil's disease was diagnosed in 31 (62%) patients, aseptic meningitis in 12 (24%) and acute unexplained fever in seven (14%). Haemodialysis was required for 11 (35%) patients with Weil's disease. Three (6%) patients died. Cause of death was massive gastrointestinal haemorrhage in two and renal failure in one. Leptospira icterohaemorrhagiae was responsible for 39 (78%) cases, Leptospira canicola for six (12%), Leptospira grippotyphosa for two (4%), and Leptospira australis, Leptospira ballum and Leptospira sejroe, for one case each. A muscle biopsy was performed in six patients and a renal biopsy in three. Focal necrotic muscular changes, with mild mononuclear infiltrate, were found. Pigmented casts in distal convoluted tubules, mild interstitial inflammatory infiltrate and mesangial enlargement of some glomeruli were observed in kidney biopsies. A good knowledge of the protean clinical manifestations of leptospirosis and an accurate laboratory study are required for a correct diagnosis.