Angelo Cazzadori

Transmission of HIV-Associated Tuberculosis to Healthcare Workers

OBJECTIVE A retrospective investigation was made to compare the occupational risk of tuberculosis in personnel assisting human immunodeficiency virus (HIV)-infected and uninfected subjects with active tuberculosis. DESIGN We retrospectively reviewed 6 years of hospital activity in 3 units where HIV-infected patients with tuberculosis are hospitalized and in 2 units where non-HIV-infected tuberculosis patients are hospitalized. The risk of occupational tuberculosis in healthcare workers who assisted HIV-infected and non-HIV-infected patients with tuberculosis was investigated. PARTICIPANTS The risk of occupational tuberculosis in healthcare workers was studied by considering the numbers of potential source cases (hospitalized patients with tuberculosis) in the two conditions investigated (HIV-positive and HIV-negative). Both potential source cases and cases of tuberculosis in healthcare workers had to be microbiologically proven in order to be considered. RESULTS Seven cases of tuberculosis occurred in persons who cared for 85 HIV-infected subjects with tuberculosis, while only 2 cases occurred in staff members who took care of 1,079 HIV-negative tuberculosis patients over the same period (relative risk = 44.4; 95% confidence interval = 8.5-438). CONCLUSIONS Tuberculosis seems no longer to be a neglectable risk in healthcare workers assisting patients with HIV infection. Further study is urgently needed to see whether such unexpectedly high dissemination of tuberculosis also is demonstrable in the community.

Aetiology of pneumonia following isolated closed head injury.

Patients undergoing mechanical ventilation (MV) after an isolated closed head injury (ICHI) have often been found to develop hospital-acquired pneumonia (HAP) well before subjects who require MV for different reasons. In a prospective study of patients receiving MV after an ICHI. 38 subjects (out of 65 with clinically suspected HAP) had a bacteriological diagnosis established on the basis of correspondence between cultures made from bronchoalveolar lavage and protected specimen brush (with quantitative thresholds of 10(4) and 10(3) cfu ml-1, respectively). Patients were separated according to the time of onset of HAP, with 20 subjects who developed HAP within 4 days of the start of MV (early onset pneumonia, EOP) and 18 subjects who developed HAP after the fourth day (late onset pneumonia, LOP). In those who had LOP, an expected spectrum of organisms was found, with Gram-negatives (especially Pseudomonas sp.) accounting for the majority of isolates. However, in EOP cases, Gram-positive bacteria (especially Staphylococcus sp. and Streptococcus pneumoniae) were found to largely predominate (P = 0.0000026). This confirms the high incidence of staphylococcal pneumonia in neurosurgery patients, and also provides evidence that the vast majority of such staphylococcal pneumonia are EOP. Unlike most previous reports, the microbiological findings from the present study suggest that a cut-off point of 4 days successfully distinguishes between EOP and LOP. Since these two clinical entities differ significantly in terms of pathogenesis and aetiology, preventive measures and therapeutical protocols have to be tailored accordingly.

The ParaSight-F rapid dipstick antigen capture assay for monitoring parasite clearance after drug treatment of Plasmodium falciparum malaria.

Three methods for the detection of Plasmodium falciparum infection in peripheral blood were compared during antimalarial treatment and follow-up in 32 Burundian patients: dipstick antigen capture assay, standard (TBF) and prolonged thick blood film examination (PTBF) (3 x 5 min and 3 x 20 min examination respectively). Parasitaemia was determined daily by comparison with total white blood cell counts (determined by Coulter counter) until no parasite was detected on 2 consecutive days by PTBF. Cumulatively, 231 observations were made with each assay: 64 were negative and 167 positive by PTBF (59 had parasite counts < or = 100/microL). Compared to PTBF, the sensitivities of TBF and the dipstick assay were 1.0 for parasite counts > 100/microL and 0.458 and 0.966 respectively for counts < or = 100/microL. Overall, the dipstick assay was significantly more sensitive (0.988 vs. 0.808; P < 0.001) but less specific (P = 0.013) than TBF. The dipstick assay is of potential use for monitoring response to drug treatment and for detecting low parasitaemias.

Lymphocyte subpopulations in active tuberculosis: association with disease severity and the QFT-GIT assay.

Cell-mediated immune response plays an essential role in the pathogenesis of tuberculosis (TB). We retrospectively evaluated lymphocyte subpopulations in 177 active TB patients compared to 93 healthy controls, finding a relevant decrease in total lymphocytes and CD8+ cells. Conversely, activated human leukocyte antigen (HLA-DR+) and CD4+CD57+ cells were higher in the TB group. B-1a (CD5+CD19+) lymphocytes were reduced in TB subjects, particularly those with extended and cavitary pulmonary forms, suggesting increased compartmentalisation at the infection site. QuantiFERON-TB Gold In-Tube positive results were associated with higher HLA-DR+CD4+ and CD4+CD57+ cells, while interferon-gamma response and total lymphocyte levels were lower in advanced pulmonary TB cases.Cell-mediated immune response plays an essential role in the pathogenesis of tuberculosis (TB). We retrospectively evaluated lymphocyte subpopulations in 177 active TB patients compared to 93 healthy controls, finding a relevant decrease in total lymphocytes and CD8+ cells. Conversely, activated human leukocyte antigen (HLA-DR+) and CD4+CD57+ cells were higher in the TB group. B-1a (CD5+CD19+) lymphocytes were reduced in TB subjects, particularly those with extended and cavitary pulmonary forms, suggesting increased compartmentalisation at the infection site. QuantiFERON®-TB Gold In-Tube positive results were associated with higher HLA-DR+CD4+ and CD4+CD57+ cells, while interferon-gamma response and total lymphocyte levels were lower in advanced pulmonary TB cases.

Tuberculosis among refugees and displaced people at the Burundi-Rwanda border

On the basis of reports from urban centers [1, 2], HIV infection is considered the major factor responsible for the increased rate of tuberculosis (TB) in sub-Saharan Africa [3]. In the Hospital of Kiremba in Burundi, 10 km from the Burundi-Rwanda border, we surveyed TB morbidity from 1992 to 1995. To test the possible influence of the ethnicity-related fighting begun in late 1993 [4] on the spread of TB, we retrospectively divided the study period into two subperiods (1992‐1993 and 1994‐1995). For all patients with current or recent histories of fever, cough, and bloody sputum and all patients with symptoms of lower respiratory tract infection (LRTI) who had failed to respond to antibiotics, Ziehl-Neelsen staining of sputum specimens for acid-fast bacilli (AFB) was undertaken. Serology for antibodies to HIV was performed by use of ELISA. The hospital patient population consisted of local rural residents and patients from urban centers of Burundi, and, since early 1994, numerous Rwandan refugees from a nearby camp [4]. Hospital admissions declined from 8,050 in 1992‐1993 to 3,112 in 1994‐1995, whereas microbiologically proven pulmonary TB cases (AFB positive) rose from 148 to 167, an increase from 1.8% to 5.4% (P o .0001). The number of patients requiring AFB testing decreased; however, the percentage increased from 24.3% during 1992‐1993 to 37.6% in 1994‐1995 (P o .0001). The AFB positivity rates were comparable during the first 3 years of the study (7.1%, 8.0%, and 9.5%), but in 1995 these values almost doubled (16.9%; P o .0001). TB associated with HIV infection accounted for 20% of the TB cases from 1992 to 1993, but this percentage decreased to 6% in 1995 (PA .007). On the basis of the proportion of TB cases per total hospital admissions and on the AFB positivity rate in 1992‐1993, we found Figure 1. Representation of the geographical area of the Hospital 107 excess TB cases in 1994‐1995. Rwandan refugees contributed of Kiremba together with a map of Burundi. Large arrows indicate significantly to this increase (58 cases, 54.2%), but 47 of the re- the major flows of demographic movement across the border. maining 49 excess cases occurred among local rural residents. A Burundi-Rwanda border; A urban centers; HA Hospital Thirty of these 47 cases involved the inhabitants of a single zone, of Kiremba; R A refugee camp. the hill of Marangara; this group accounted for nearly 20% of hospital attendance in both subperiods, but the percentage of TB cases among these residents rose from 2% in 1992‐1993 to 7.2% since 1994), which preceded the subsequent major increase in the

Tentative reference values for some elements in broncho-alveolar lavage fluid.

The concentrations of Fe, Mn, Pb and Cr have been determined in broncho-alveolar lavage (BAL) fluid of 25 subjects without occupational or abnormal environmental exposure to metals, using the AAS method. The numerous factors which can interfere with the results in pre-analytical and in analytical phases are stressed. Metals concentrations in BAL are expressed in micrograms/l. They were not correlated with the volume of fluid recovered, the total cells, alveolar macrophages and erythrocytes. The results were not modified by stratification considering age and sex. Iron concentrations were higher than others, probably due to higher environmental exposure and partly to its essential role in humans. The diagnostic significance of element determination in BAL fluid and the relationship with exposure and lung load is discussed.

Pharmacokinetics of antimicrobial agents in the respiratory tract

The ability of antibiotics to penetrate into the respiratory tract has been investigated at several sites, namely, sputum and bronchial secretions, tissue homogenates, pleural fluid and, more recently, epithelial lining fluid and alveolar macrophages. The major reason for such investigations is that these data may be helpful to a more thorough understanding of drug distribution in the lung tissue and fluids and to a more accurate prediction of clinical outcome. However, the study of drug concentration at each of these sites presents problems in terms of methodology and data interpretation. The advantages and disadvantages of each of these methods are considered, and the data on penetration of betalactams, aminoglycosides, macrolides, fluoroquinolones and other antimicrobial agents (including antifungal and antiprotozoan drugs) are reviewed.

Staphylococcal Sepsis Delaying Diagnosis and Treatment of Vertebral Tuberculosis

Between January 2000 and January 2002 we observed five cases of staphylococcal sepsis associated with tuberculous spondylitis, an intriguing association because of the microbiological, diagnostic and therapeutic consequences. All of the patients had been admitted to our unit with a definite diagnosis of sepsis due to methicillin-sensitive Staphylococcus aureus. They had all been adequately treated for an appropriate duration (at least 3 weeks of intravenous therapy) according to the antimicrobial sensitivity patterns. Nonetheless, despite the improvement in their general physical condition and most of the laboratory values, focal vertebral signs became evident and inflammation indicators remained elevated. A thorough diagnostic work-up to identify a cryptic localization of the infectious process gave evidence of spondylitis. In all cases either computed tomographic (CT) scan or magnetic resonance imaging (MRI) of the spine was performed. All patients were male (age range 35 /73 years). Three were Italian, one was Brazilian and one was Senegalese. They all were negative both at the imaging of the lung and at the tuberculin skin testing. Only one was known to be human immunodeficiency virus (HIV) positive. Four of them had previously undergone invasive procedures, antalgic (because of back pain) in 2. In all cases the antimicrobial regimens consequently adopted to treat spondylitis contained either rifampicin or a fluoroquinolone (also active agents against tuberculosis) or both, because of their antistaphylococcal activity and their advantageous distribution into bone (1). Nonetheless, in all cases despite at least 6 weeks of antibiotic treatment, no clinical and radiological improvement could be shown. Indeed, in 3 patients the disease progressed both clinically and radiologically. Eventually, Mycobacterium tuberculosis was isolated in vertebral biopsies in 3 cases and histological features consistent with tuberculosis were found in biopsies from the other 2. The administration of an adequate antitubercular regimen, for at least 9 months, was successful in all 5 cases (2). It is noteworthy that 2 subjects underwent invasive procedures because of persistent back pain; perhaps this unspecific symptom was the only slim evidence of unrecognized tuberculosis of the spine. However, no other epidemiological, clinical or laboratory data indicated such a specific process. From an epidemiological standpoint, only 1 patient, HIV positive and originating from a country with a high prevalence of tuberculosis, could be strongly suspected of having a coinfection. Lung imaging was negative, as was tuberculin skin testing (as expected in case of a concomitant sepsis). Lastly, the treatment played a critical role. The spondylitis, initially attributed to a secondary staphylococcal localization, had been treated with antibiotics active against both S. aureus and M. tuberculosis. This choice may have negatively affected the sensitivity of cultural procedures, which is deceptive even in ideal conditions (3, 4), making the diagnostic process more difficult.

Invasive Pulmonary Aspergillosis after Renal Transplantation Treated by Surgery

Invasive pulmonary aspergillosis is a serious complication in immunocompromised patients. In those unresponsive to pharmacological treatment, or when drug toxicity is excessive, surgery may resolve the condition. A 48-year-old woman with invasive pulmonary aspergillosis after renal transplantation underwent resection of the right upper lobe and the apical segment of the inferior lobe, followed by complete recovery.