Analysis of risk factors for laboratory-acquired brucella infections

Analysis of risk factors for laboratory-acquired brucella infections

Journal of Hospital Infection (2004) 56, 223–227 www.elsevierhealth.com/journals/jhin Analysis of risk factors for laboratory-acquired brucella infe...

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Journal of Hospital Infection (2004) 56, 223–227

www.elsevierhealth.com/journals/jhin

Analysis of risk factors for laboratory-acquired brucella infections ¨ . Ergo ˘uza ¨nu ¨la,*, A. C ¨venerb, B. Dokuzog ¸elikbas ¸a, D. Tezerenb, E. Gu O a

The First Infectious Diseases and Clinical Microbiology Clinic, Ankara Numune Education and Research Hospital, Ankara, Turkey b The First Microbiology and Clinical Microbiology Laboratory, Ankara Numune Education and Research Hospital, Ankara, Turkey Received 19 July 2003; accepted 23 December 2003

KEYWORDS Laboratory-acquired; Brucella infection; Risk factors

Summary The aim of the study was to determine the risk factors for acquiring brucella infection among healthcare workers (HCWs). The study was performed in Ankara Numune Education and Research Hospital, Turkey, before the introduction of Biosafety III measures. A questionnaire was given to HCWs, who were at risk of brucella infection. Twelve HCWs with brucella infection were detected, an incidence of 8% per employee-year. A multivariate analysis of risk factors in seven of the cases and 48 control HCWs was performed. Male physicians were found to be associated with a higher risk of acquiring brucella infection [odds ratio, 25.3; confidence interval (CI), 2.3 – 283.7; P ¼ 0:008]. Using gloves was found to be protective (odds ratio, 0.02; CI, 0.008 – 0.4; P ¼ 0:017). Q 2004 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved.

Introduction Brucella spp. are a leading cause of laboratoryacquired bacterial infections,1 and have been reported in both brucella-endemic and brucellafree countries since 1941.2 – 5 Laboratory-associated infections represent 2% of all reported cases of brucellosis,1 – 6 demonstrating the high risk of acquiring brucella infection in clinical microbiology laboratories where these highly infective bacteria are handled. Transmission occurs usually via *Corresponding author. Address: Guvenlik caddesi 17/10, 06540 Asagi Ayranci, Ankara, Turkiye. Tel. þ 90-312-4194227. E-mail addresses: [email protected]; mergonul@hsph. harvard.edu

inhalation of bacteria, allowing entry of brucella through the respiratory mucosa.1 – 5 Transmission routes other than aerosol inhalation have been defined, although some of them are speculative. The risk factors for acquisition of infection among healthcare workers (HCWs) have not been previously reported. Brucellosis is endemic in Turkey, and as a consequence, the inhalation route of transmission among microbiology laboratory workers is important. However, laboratory-acquired infections are rarely diagnosed or reported. The Occupational Health and Safety Committee in our hospital targeted the control of laboratory-acquired infections in HCWs. This study presents clinical and laboratory findings of laboratory-acquired

0195-6701/$ - see front matter Q 2004 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jhin.2003.12.020

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brucellosis, and the analysis of the risk factors for brucella infection among the HCWs, who are actively working in laboratories.

absence of a biosafety cabinet, ignorance of safety precautions and personal protection, lack of laboratory material, were sought.

Data analysis

Methods Hospital setting The study was conducted at the Ankara Numune Education and Research Hospital, one of the largest referral tertiary-care community hospitals in Turkey. The hospital has 1100 patient beds, with approximately 36 000 patient discharges a year. The microbiology laboratory processes approximately 400 brucella-positive cultures per year. An Occupational Health and Safety Committee was recently established, and targeted the risk factors for occupational infections, as a priority.

Brucellosis cases The study included the brucellosis cases who were HCWs in the same hospital and/or HCWs diagnosed and treated from 2000 to 2003 by the First Clinical Microbiology and Infectious Diseases Clinic of the hospital. Cases with a history of ingestion of unpasteurized dairy products were excluded from the study. Case definition for brucellosis included a clinical illness characterized by acute or insidious onset of fever, night sweats, undue fatigue, anorexia, weight loss, headache, and arthralgia, with isolation of Brucella spp. from clinical specimens or a single Brucella agglutinin titre $ 1:320.

Risk factors for the infection All HCWs who were at risk of brucella infection were given a structured questionnaire to complete. The demographic information requested included age, gender, profession, department, duration of work, recent work with brucella-positive specimens, use of protective clothing (gloves, gown, surgical masks, and goggles), and compliance with safety precautions. The second part of the survey targeted those HCWs who had been diagnosed with brucellosis and treated. The ingestion of unpasteurized dairy products or contact with infected animals or their tissues were determined. The survey included clinical information and laboratory results. The hospital charts of the hospitalized HCWs were also used to obtain as much information as possible about their clinical courses. Possible reasons for infection, such as shortage of protective equipment, inappropriate design of the laboratory,

Data were analysed using Stata Statistical Software, version 8.0 (Stata corporation, TX, USA). Mean comparisons for continuous variables were done using independent groups t-tests. Proportion comparisons for categorical variables were done using chi-square tests, although Fisher’s exact test was used when data were sparse. The incidence of brucellosis among HCWs was calculated by the number of cases in our hospital, divided by person years in the same hospital between 2000 and 2003. Multivariable logistic regression modelling was used to compute the odds ratios (ORs) of variables predictive of brucella infection, using a stepwise backward selection approach. The independent variables were gender, age, duration of work, recent work with brucella bacteria, and compliance to safety precautions such as donning gloves, masks, and gowns. The model was limited to the HCWs who have been under sustained risk and who were expected to use safety precautions. These professional groups were physicians and laboratory technicians who were working in bacteriology laboratories. Significance was set at P , 0:05 using two-sided comparisons.

Results The demographic, clinical and laboratory characteristics of the 12 laboratory-acquired brucella cases are shown in Table I. Two of the cases (one physician and one laboratory technician) were employees of another community hospital. The attack rate for laboratory-acquired brucella infection was calculated as 18% (10/55) per HCW at risk, and 8% (10/125) per employee-year. Those physicians at risk were actively working in clinical microbiology or infectious diseases and clinical microbiology departments. More than half of the cases (67%) were male. The most common symptoms were fever, arthralgia, headache, fatigue, although one HCW had spondylodiscitis. The majority of the cases (83%) had brucella agglutinin titres $ 1:640. The brucella agglutinin titres of non-cases were zero except in one HCW, who had titre of 1:80 without any symptoms or signs of brucellosis. Seven of the patients had positive blood cultures for brucella, though only three isolates could be speciated, which were all Brucella

Analysis of risk factors for laboratory acquired brucella infections

Table I Characteristics of 12 brucellosis cases Complaints

Number (%) N ¼ 12

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Table II Univariate analysis for the risk factors of brucella infection among physicians and laboratory technicians who are at risk Cases

Professions Physicians Laboratory technicians Nurse Secretaries Staff disposing contaminated laboratory material Mean age (years) Females Presenting symptom(s) Fever, headache, fatigue Arthralgia Fever, arthralgia, headache, fatigue Fever and arthralgia Fever, arthralgia, irritability, psychological changes Fever, fatigue, loss of appetite, tinnitus Serum tube agglutination 1:320 1:640 1:1280 1:5120 Blood culture positive Serotypes Brucella melitensis biovar 3 Brucella melitensis biovar 1 Not determined Complication Spondylodiscitis Probable reason for infection Processing cultures Disposing of laboratory material Eating and drinking near the microbiology bench

6 (50) 1 (8) 1 (8) 2 (17) 2 (17) 34.7 4 (33) 3 (26) 3 (26) 2 (16) 2 (16) 1 (8) 1 (8) 2 (16) 5 (42) 3 (26) 2 (16) 7 (58) 2 (16) 1 (8) 9 (76) 1 (8) 7 (58) 2 (16) 3 (26)

melitensis, two were biovar 3, and one was biovar 1. All the patients except one spondylodiscitis case were treated by doxycycline 100 mg bid and rifampicin 600 mg a day for six weeks. The patient with spondylodiscitis was treated for six months, and in addition ceftriaxone 1 g bid was given for three weeks. The most common probable reason that could be related to infection was handling and processing the cultures (Table I). Risk factor analysis was performed on seven brucella cases and 48 controls (Table II). Sixty-two percent of 55 HCWs were female, whereas six out of seven brucellosis cases (86%) were male. In univariate analysis, both male and female physicians working in clinical microbiology, and infectious diseases and clinical microbiology clinics had a significantly higher risk for brucella infection (P ¼ 0:021 and P ¼ 0:041; Table II). The age of the

Non-cases

Subjects 7 48 Physicians working in bacteriology laboratories Male 5 6 Female 1 20 Technicians working in bacteriology laboratories Male 1 9 Female – 13 Mean age (years) 33.4 33.6 Mean duration of work 5.4 6.3 Recent work on brucella 4 11 bacteria Brucella agglutinin titre .160 Compliance to safety 7 0 precautions Wearing gloves Always 1 14 Sometimes 3 30 Never (reference) 3 1 Wearing a gown Always 0 2 Sometimes 0 3 Never 7 40 Wearing a surgical mask Always 0 1 Sometimes 3 21 Never (reference) 4 23 Wearing goggles Always 0 1 Sometimes 0 0 Never 7 44

P-value

0.021 0.041 0.439 N/A 0.645 0.673 0.414

0.005

N/A

0.544

N/A

N/A, non-applicable.

HCW ðP ¼ 0:645Þ; duration of work (experience; P ¼ 0:673), and recent work with brucella bacteria ðP ¼ 0:414Þ were not significant risk factors for the development of brucella infection. Only one HCW at risk complied with safety precautions by wearing goggles and a mask (Table II). The use of gloves always or sometimes was more protective than nonuse of gloves ðP ¼ 0:005Þ: The rate of female HCWs using gloves always or sometimes was more than that of males (97% versus 84%), although the difference was not significant ðP ¼ 0:089Þ: In the multivariate analysis male physicians were found to be associated with a higher risk of brucella infection [odds ratio, 25.3; confidence interval (CI), 2.3 – 283.7; P ¼ 0:008]. Using gloves was found to be protective (odds ratio, 0.02; CI, 0.008 – 0.4; P ¼ 0:017). These results have been adjusted for recent work with brucella, duration of work (experience), and age. The possible structural and individual reasons for infections were surveyed. The majority of the cases among physicians or laboratory technicians stressed

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the inappropriate layout of the laboratory, lack of laboratory material, the shortage of safety equipment, and lack of a biosafety cabinet. Four of 10 cases (40%) indicated that they had not thought about the risk, and only one HCW agreed that the risk had been ignored. All the physicians and laboratory technicians who had brucella infections, recommended using gloves, gowns, goggles, and masks to their colleagues in order to be protected from future infection hazards.

Discussion The potential hazard of Brucella spp. to laboratory workers has long been recognized, and has been the most commonly reported laboratory-associated bacterial infection.6 In an extensive survey performed 25 years ago, Brucella spp. accounted for 18% of overall laboratory-acquired infections, and 31% of the laboratory-acquired bacterial infections.6 The World Health Organisation categorizes Brucella spp. as a risk group III pathogen, meaning that it poses a high risk to individuals but a low risk to the community. The majority of cases, who had been reported previously, had been infected with B. melitensis.3, 5,7 – 14 B. melitensis is known as the most contagious of the brucella species,4 and five times more common than Brucella abortus in our hospital (unpublished data). Three speciated isolates were identified as B. melitensis, of which two were biovar 3, a biovar common in France, Spain, Portugal, Greece and Turkey.9 Laboratory-acquired brucellosis is not always due to occupational accidents in the majority of cases,15 and other possible routes have been reported such as direct contact, inoculation through needle-stick injuries, and contamination of skin and mucous membranes through spills or splashes into eyes, mouth or nose.1,12 The number of HCWs affected by brucellosis confirms the high risk of transmission of the infection after laboratory accidents, despite appropriate safety precautions, and the fast aerosol spread of the infection.7,8,16 Two of the cases were housekeeping staff responsible for disposal of the contaminated laboratory material, they used gloves and gowns, but never goggles or masks. Three cases (two secretaries, one nurse) were eating and drinking near to the culture-processing bench. They had never used any safety equipment. These five HCWs were unaware of the hazards of aerosol transmission of brucella. The risk of brucella infection, which occurred in these five cases, could be removed by

not allowing untrained personnel into the laboratory, no eating or drinking in the laboratory, and by sealing contaminated laboratory material before disposal, as described in Biosafety III measures.17 These five particular infection cases were not included in the risk factor analysis, because there were no other comparable controls. Therefore, risk factor analysis was limited to physicians and laboratory technicians, including the other seven cases and 48 controls. Approximately 70% of infectious diseases physicians or microbiologists are female in Turkey. Although the females are predominant in the profession, there was only one who was infected (Table II). The male HCWs used gloves less often than females, whilst working in the bacteriology laboratory (84% versus 97%). There was no biosafety cabinet in the microbiology laboratory. The laboratory workers used goggles, masks, and gowns only rarely (Table II). Gloves were the most commonly used protective equipment, the use of which was found to be protective against brucella infection in our multivariate analysis (odds ratio, 0.02; CI, 0.008 – 0.4; P ¼ 0:017). Gloves could be a barrier to prevent the transmission from contaminated hands to the mouth or nose. Although their own compliance was low (Table II), the infected HCWs recommended the use of gloves, gowns, goggles and masks to their colleagues in order to prevent brucella infection. Sniffing culture plates is another risk factor, a common practice in bacteriology laboratories in Turkey, as in other countries.13 The prohibition of sniffing cultures has already been suggested,13 and this suggestion should be adopted in bacteriology laboratories throughout our country. As a result of this study, the Occupational Health and Safety Committee has decided to implement new control measures in collaboration with hospital management, including the provision of Biosafety III precautions.

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