Benedetta Allegranzi

Evidence-based model for hand transmission during patient care and the role of improved practices

Hand cleansing is the primary action to reduce health-care-associated infection and cross-transmission of antimicrobial-resistant pathogens. Patient-to-patient transmission of pathogens via health-care workers hands requires five sequential steps: (1) organisms are present on the patients skin or have been shed onto fomites in the patients immediate environment; (2) organisms must be transferred to health-care workers hands; (3) organisms must be capable of surviving on health-care workers hands for at least several minutes; (4) handwashing or hand antisepsis by the health-care worker must be inadequate or omitted entirely, or the agent used for hand hygiene inappropriate; and (5) the caregivers contaminated hand(s) must come into direct contact with another patient or with a fomite in direct contact with the patient. We review the evidence supporting each of these steps and propose a dynamic model for hand hygiene research and education strategies, together with corresponding indications for hand hygiene during patient care.

The antimicrobial resistance containment and surveillance approach - a public health tool

Antimicrobial drug resistance (AMR) is widely recognized as a global public health threat because it endangers the effectiveness of treatment of infectious diseases. In 2001 WHO issued the Global Strategy for Containment of Antimicrobial Resistance, but it has proved difficult to translate the recommendations of the Global Strategy into effective public health actions. The purpose of the Antimicrobial Resistance Containment and Surveillance (ARCS) approach is to facilitate the formulation of public health programmes and the mobilization of human and financial resources for the containment of AMR. The ARCS approach highlights the fundamental link between rational drug use and containment of AMR. Clinical management of human and animal infections should be improved through better disease control and prevention, high quality diagnostic testing, appropriate treatment regimens and consumer health education. At the same time, systems for supplying antimicrobial drugs should include appropriate regulations, lists of essential drugs, and functional mechanisms for the approval and delivery of drugs. Containment of AMR is defined in the ARCS approach as the continuous application of this package of core interventions. Surveillance of the extent and trends of antimicrobial resistance as well as the supply, selection and use of antimicrobial drugs should be established to monitor the process and outcome of containment of AMR. The ARCS approach is represented in the ARCS diagram (Fig. 2) which provides a simplified, but comprehensive illustration of the complex problem of containment and monitoring of AMR.

Comparative histopathological study of pulmonary tuberculosis in human immunodeficiency virus-infected and non-infected patients

SETTINGnClinical features of human immunodeficiency virus (HIV)-associated tuberculosis depend upon the patients residual immunity. An immune-dependent presentation has also been described at the histopathological level in many extra-pulmonary sites, but no descriptions have so far been made on the histopathology of HIV-associated pulmonary tuberculosis.nnnOBJECTIVEnTo compare the histopathological features of pulmonary tuberculosis in HIV-infected subjects and seronegative patients.nnnDESIGNnWe carried out a retrospective comparative study on 16 HIV-infected subjects and 16 seronegative patients with culture-proven pulmonary tuberculosis who underwent transbronchial biopsy. We evaluated the bacillary burden and the parenchymal inflammatory reaction by means of a four-graded scoring system giving an approximate quantitative measure of the two parameters.nnnRESULTSnHIV-associated pulmonary tuberculosis was found to differ significantly from disease forms seen in seronegative patients, with a significant tendency to develop highly bacillary and poorly reactive histopathological pictures along with the downgrading evolution of immune function.nnnCONCLUSIONnPathologic features of pulmonary tuberculosis in HIV-infected subjects differ from those encountered in seronegative patients depending upon the individual immunity of the former. HIV-associated progressive depletion of CD4+ lymphocytes leads to substantial changes in pulmonary reactivity to Mycobacterium tuberculosis; multibacillary pictures in a background of loose inflammatory reactions are quite common findings at the extreme phase of HIV-related immune deterioration.

Considerations for a WHO European strategy on health-care-associated infection, surveillance, and control

n Summaryn n Health-care-associated infection (HAI) is a major issue of patient safety with a substantial impact on morbidity, mortality, and use of additional resources worldwide. In April 2004, the WHO Regional Office for Europe organised the first international consultation to address the issue of HAI in eastern and central Europe. The main objectives of the consultation were to identify the primary needs and obstacles for the prevention and control of HAI at country level, to design the essential components of an international strategy to effectively address the issue of HAI, and to identify specific priorities and recommendations for interventions by the WHO and other international institutions. An update on HAI activities and related networks throughout Europe, together with the outcome of the meeting, are presented, with special emphasis on future considerations for a European WHO strategy on HAI prevention.n n

Imported Malaria in Adults and Children: Epidemiological and Clinical Characteristics of 380 Consecutive Cases Observed in Verona, Italy

BACKGROUNDnSince the year 2000, in Italy, there has been a constant decrease in the number of cases of imported malaria in immigrants. Nevertheless, immigrants still account for about 70% of reported cases. To our knowledge, no data are yet available on imported malaria in children. This paper describes the main characteristics of malaria cases observed in recent years in the three main hospitals in Verona (roughly representing 10% of all cases reported in Italy in the period), with a special focus on the poorly known problem of imported malaria in children.nnnMETHODnAll malaria cases occurring from 2000 to 2004 were retrospectively examined. Semi-immune and nonimmune patients were analyzed for clinical, laboratory, and parasitological findings. A separate analysis was carried out for children who traveled to endemic areas to visit relatives and friends (VRF) and children born in endemic countries who came to Italy for immigration purposes.nnnRESULTSnA total of 380 cases of imported malaria occurred in Verona in the 5-year period, 43 being children. Semi-immune patients had a significantly lower parasitemia (p = 0.0032) and parasite clearance time and significantly shorter fever duration than nonimmune (p = 0.025 and p = 0.0026). VRF children presented significantly higher parasitemia and significantly lower platelet count (p = 0.016 and p = 0.042) than recent immigrants. Parasitemia clearance time and fever duration were longer in VRF children than in recent immigrants (p = 0.014 and p = 0.0085). We observed 23 cases of severe malaria, including 4 cases in immigrants.nnnCONCLUSIONSnOur data confirm a significant difference both in clinical and in parasitological findings between semi-immune and nonimmune patients. We identified two populations of immigrant children: semi-immune (recent immigrants) and nonimmune (VRF). The latter is a high-risk group for severe malaria. Educational actions should be specially designed for immigrants traveling to VRF, focusing on the risk of severe malaria for both adults and children.

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.

Response of uncomplicated falciparum malaria to oral chloroquine and quinine in Burundi highlands

The in vivo response of falciparum malaria to oral chloroquine and quinine was evaluated in two identical hospital-based, comparative open trials carried out 2 years apart in the same seasonal period at a hospital located in the highlands of Northern Burundi. Children aged 0-14 with uncomplicated falciparum malaria were administered either chloroquine, at 25 mg/kg over 3 days, or quinine, at 10 mg/kg per 8 hourly for 5 days (alternate allocation) and treatment response was evaluated by the WHO 7-day test. In the first study (1992/1993) 472 patients qualified for analyses (211 in the chloroquine and 261 in the quinine group), as compared to 249 subjects in the second study (1994/1995). In each study, the response to quinine was significantly higher than that to chloroquine (P = 0.004 and < 0.001, respectively). While the response to quinine showed insignificant changes over time (95.8 vs. 92.9%), chloroquine was found to be significantly less effective in the second study as compared to the first (77.8 vs. 63.1%; OR (95% CI) 2.04 (1.21-3.43)). Such decline in chloroquine efficacy was attributable to the age group < 5 years of age, where response to chloroquine decreased from 72.9% in 1992/93 to 56% in 1994/1995. Uncontrolled chloroquine use, which spread after the onset in late 1993 of the still ongoing ethnic fighting, appears to be the most likely reason for such a decrease in chloroquine efficacy. Chloroquine resistance has long been known to be present in the hyperendemic lowlands of Burundi, but no data have so far been reported on the response to antimalarials in the highlands of the country. These findings should be considered when deciding on drug policies for the treatment of falciparum malaria in Burundi.

Penetration of Orally Administered Prulifloxacin Into Human Lung Tissue

ObjectiveTo evaluate the distribution in lung tissue of ulifloxacin, the active metabolite of prulifloxacin, a new once-daily fluoroquinolone administered orally in a single 600mg dose.DesignOpen-label, randomised study.PatientsTwenty-seven patients (25 males, 2 females; mean age 65.7 years [range 49–79 years]) with a lung neoplasm requiring lobectomy or pneumonectomy.MethodsPatients were randomly assigned to five treatment groups and received a single oral dose of prulifloxacin 600mg at 2, 4, 6, 12 or 24 hours preoperatively. During surgery, blood and healthy lung (based on macroscopic appearance) samples were collected at the same time. Ulifloxacin concentrations in plasma and lung tissue were determined by a validated reversed-phase high-performance liquid chromatography assay. Lung tissue ulifloxacin concentrations were adjusted for blood contamination, by measuring haemoglobin in the supernatant of each tissue sample and applying a corrective equation.ResultsUlifloxacin concentration in lung tissue exceeded plasma concentration at every timepoint. Following administration of prulifloxacin 600mg, the overall mean corrected lung/plasma ratio over the 24-hour period was 6.9 (range 1.2–14.1). When sampling intervals were assessed, the corrected lung/plasma ratios were 7.5 (2 hours after dosing), 6.3 (4 hours), 4.3 (6 hours), 7.0 (12 hours) and 9.2 (24 hours). The mean corrected lung/plasma area under the concentration-time curve ratio was 6.3, demonstrating the ability of the drug to penetrate lung tissue and confirming the high exposure of this target tissue to ulifloxacin. However, the limitation of the lung tissue sampling method and the high interpatient variability should be considered. Over the 24-hour period, the concentrations of ulifloxacin in lung tissue were higher than the minimum inhibitory concentration (MIC) values for pathogens frequently involved in community-acquired respiratory tract infections.ConclusionLung tissue penetration data may have a supportive value when considered jointly with MICs and efficacy results. The findings from this lung penetration study could explain the efficacy of once-daily prulifloxacin 600mg observed in clinical trials conducted in patients with exacerbation of chronic bronchitis.

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

Hand Hygiene: A Handbook for Medical Professionals

• Developed and presented by the world leaders in this fundamental topic • Fully integrates World Health Organization (WHO) guidelines and policies • Offers a global perspective in tackling hand hygiene issues in developed and developing countries • Coverage of basic and highly complex clinical applications of hand hygiene practices • Includes novel and unusual aspects and issues in hand hygiene such as religious and cultural aspects and patient participation • Offers guidance at the individual, institutional, and organizational levels for national and worldwide hygiene promotion campaigns