Chapter 11: Biosafety and Hospital Control
by Maria Alice Telles and Afranio Kritski
11.1. Biosafety in the hospital
Tuberculosis (TB) drug treatment can be carried out mainly at the ambulatory level, but the diagnosis of the disease is not always accomplished in the ambulatory setting. In big cities of developing countries, the diagnosis of TB is often made in the hospital before these patients are assisted at the local or regional outpatient centers. The reference treatment centers for hospitalizing TB patients are frequently the only health centers with specialized ambulatory facilities for assisting these patients, including those with co-morbidities. The percentage of patients diagnosed in hospitals may be 30 % or even higher. This kind of situation favors the exposure to TB infection in the nosocomial environment.
Around 25 to 50 % of the persons exposed to an intimate contact with active pulmonary TB will become latently infected with Mycobacterium tuberculosis. Exposure to the index case for 12 or more hours implies a high risk of infection, especially in closed environments without biosafety precautions. Immunosuppressed persons have an increased risk of infection and active disease compared with immunocompetent persons. Initially, the evaluation of the risk of transmission of TB within a health institution can be classified as follows:
- Low, if the institution admits less than six patients with active pulmonary TB per year or if it has more than 100 healthcare professionals per hospitalized pulmonary TB patient per year;
- High, if there are less than 10 healthcare professionals per hospitalized pulmonary TB patient per year (Menzies 1995, Hopewell 1986, Harries 1997).
In the last decade, high rates of drug-resistant TB have been described in prisons and hospitals. Thus, it is essential that health facilities are adequate to assist patients with active pulmonary TB or those suspected of having TB in order to reduce the risk of M. tuberculosis transmission to healthcare personnel and other sick people, mainly immunosupressed patients.
11.1.2. Healthcare Units
TB biosafety measures are often neglected. This increases the possibility of M. tuberculosis nosocomial transmission. During the ’90s, transversal and longitudinal studies were accomplished on the risk of TB infection in general, as well as in reference and teaching hospitals in developed and developing countries. These studies identified a high rate of nosocomial transmission of TB to medicine, nursing, and physiotherapy students, as well as to healthcare personnel (Roth 2005, Alonso-Echanove 2001, Kruuner 2001, Harries 1997, Cuhadaroglu 2002, Do 1999, Tan 2002, Silva 2002, Resende 2004).
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11.1.3. Tuberculosis infection control activities Assuming the political commitment of the managers of public or private hospitals and the fulfillment of the international legislation suggested by the World Health Organization (WHO), TB transmission control measures in a health unit can be hierarchized into three levels: administrative, engineering, and individual protection (Jensen 2005, World Health Organization 1999, British Thoracic Society 2000). Initially, the administrative measures can be deemed the most important. Besides being comprehensive, they are generally related to the permanent education and training of the healthcare personnel aimed at the implementation and appropriate fulfillment of the established norms. The administrative measures include the evaluation of: Number of pulmonary TB cases assisted annually in the health unit · Number of annual pulmonary TB cases among the healthcare personnel · Risk profile of the unit, by sector: – Low: < 6 pulmonary TB patients per year – Intermediate: = 6 pulmonary TB patients per year and an annual average risk of TB infection (tuberculin skin test conversion) lower than 2 % among healthcare personnel – High: = 6 patients with pulmonary TB and an annual risk of TB infection among healthcare personnel higher than 2 % · Areas that potentially present a higher risk of transmission: – respiratory isolation rooms – ambulatory and phthisiology waiting rooms – thoracic radiology room – bronchoscopy and sputum induction rooms – pentamidine nebulization room – ventilatory assistance areas – day-hospital – emergency rooms – autopsy room – microbiology/mycobacteria laboratory 11.1.4. General practices 22.214.171.124. Management of hospitalized pulmonary tuberculosis patients · The head nurse of the unit must have autonomy to isolate the patient if there is clinical suspicion of airborne TB. · The patient in isolation must stay under the responsibility of the service that admitted him/her. · The patients in isolation must be instructed to cover their mouth and nose when they cough or sneeze, even inside their room. · The tests to be accomplished on the patients in isolation should be done as soon as possible, so that they spend a minimum time outside their room; the patient should not wait for the tests in the waiting rooms of the different services. · When the patient needs to leave the room, a surgical mask must be used. · Healthcare personnel must avoid unnecessary entry into the isolation rooms; in the same way, the number of visitors and attendants should be restricted to the smallest number possible. In this case, everyone should enter the isolation room using special masks (N95 or PFF2 respirators). · In case of need, the priority in the isolation will be given to patients with acid fast bacilli (AFB) smear-positive microscopy results (bacilliferous) and shorter time of treatment. · The patients with airborne TB (or suspicious cases) still in the infectious period should not be submitted to surgery unless in case of emergency. · The hospital discharge of respiratory TB patients should be accomplished in the shortest possible time span. Case searching Instruct the healthcare personnel in the screening area, emergency department, at the admission and discharge area to suspect TB in: · respiratory symptomatic patients (cough with expectoration for more than three weeks) · contacts of active pulmonary TB cases for more than 12 hours · pulmonary TB radiological suspects · persons with predisposition to TB (immunosuppression, diabetes) Diagnosis · Ready request, accomplishment and release of the sputum AFB smear microscopy results in persons with presumptive TB diagnosis · AFB smear microscopy result in 24 hours, at most · Optimization of the diagnostic procedures, implementation of M. tuberculosis complex identification techniques and of anti-tuberculosis drug susceptibility testing Every healthcare professional with signs or consistent symptoms of pulmonary TB should seek medical help and be submitted to laboratory tests (sputum AFB smear microscopy, when clinical specimen is available) and thoracic radiography. Until the pulmonary TB diagnosis is ruled out or the patient is considered non-infectious, healthcare workers with pulmonary disease should stay away from their activities. Healthcare personnel must be informed that patient care activities are not suitable for those harboring an immunosuppressive condition, such as human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), malign neoplastic disease or deficient cellular immunity. HIV testing and counseling should be offered to all healthcare professionals. Creation of a TB control committee responsible for: · evaluating annual trends of M. tuberculosis drug resistance in the institution · identifying transmission risk areas · performing operational studies for the surveillance of compliance with biosafety norms · accomplishing biosecurity educational activities for the healthcare personnel · accomplishing periodic tuberculin skin testing in the healthcare personnel · preventing recently infected persons from becoming ill; indicating chemoprophylaxis to the healthcare personnel with latent TB infection. 126.96.36.199. Guidelines for patient isolation · Suspected or confirmed airborne TB cases · HIV-positive respiratory symptomatic patient with any change in thoracic X-ray · HIV-negative patient with a radiological image suggestive of pulmonary TB (hypotransparency in the superior lobes of the lung or in segment six, or with a diffuse micronodular infiltration, suggestive of miliary disease · Patient with a request for sputum AFB microscopy examination and/or culture · The head nurse of the unit must have autonomy to isolate the patient if there is clinical suspicion of respiratory TB Respiratory isolation area · Must be an individual room, with the door closed and windows that can be opened · If absolutely necessary, two pulmonary TB patients can share an isolation room, provided they both have confirmed TB diagnosis and there is no epidemiological suspicion of drug-resistant TB (such as patients that have not received previous treatment and have not had contact with drug-resistant TB cases). Time for discharge from respiratory isolation · In confirmed TB cases under a treatment scheme containing rifampicin: after two weeks of treatment and with three sputum AFB smear-negative results or one induced sputum or bronchoalveolar lavage AFB smear-negative result · In confirmed TB cases under a treatment scheme not containing rifampicin: after four weeks of treatment and with three sputum AFB smear negative results or one induced sputum or bronchoalveolar lavage AFB smear-negative result · If one of the tests is positive, repeat the series after one week · In suspicious cases: with three negative sputum-smear microscopy or one induced sputum or bronchoalveolar lavage with negative AFB smear microscopy 188.8.131.52. Ambulatory assistance under a standardized Reference Health System · Signal the TB risk areas of the unit · Avoid movements of confirmed or suspected TB patients inside the health unit in order to minimize contact with people awaiting assistance for other ambulatory specialties in waiting or examination rooms · In outpatient units where ambulatory patients with pulmonary TB and conditions other than TB are assisted in the same places and/or by the same healthcare personnel, consultation appointments should be separated in different hours or days, in such a way to avoid TB exposure of uninfected persons, mainly those who are immunosuppressed · Avoid crowding in the waiting rooms, assigning consultations to specific days for TB and setting a time for consultation, giving priority to the assistance of infectious patients and suspicious cases, thus avoiding the gathering of potentially infectious patients · Avoid assisting immunosuppressed patients and children less than 5 years old in rooms contiguous to the ones assisting TB patients · Offer surgical masks or tissue paper to infectious or suspected TB patients, mainly when circulating through the unit (specialist consultation, X-ray exams, sputum delivery to the laboratory, search for exam results, etc.) · Instruct patients to cover their mouth and nose when they cough or sneeze. 184.108.40.206. Engineering measures Engineering measures for TB control are architectural and technical devices aimed at the adaptation of the unit, or of a certain area, to provide care to pulmonary TB patients. The implementation of such measures contributes to decreasing the risk of TB transmission and should be directed by qualified personnel with special knowledge on the characteristics of TB transmission. Objectives Basically, the objective is the removal or dilution of infectious particles taking into account the following factors: · Ventilation exhaustion: captures and removes contaminants suspended in the air near the source (patient) · General ventilation: ventilation rate or number of air changes per hour; for example, a complete air exchange per hour of a certain area reduces the concentration of infectious particles by 63 %, while six complete exchanges are needed to reduce it by 99 % · Direction of the air flow within the facilities: contains the contaminated air in a certain area of the facility and prevents spread into non-contaminated areas · Negative pressure in the room with directional flow: contains the contaminated air in a certain area of the room and prevents spread to non-contaminated areas · Adjustment of air flow pattern inside the room: prevents air stagnation short circuit · Air filters and/or ultraviolet (UV) light: disinfect air High efficiency particulate air (HEPA) filters HEPA filters or absolute filters are those able to remove 99.97 % of particles with a diameter larger than 0.3 µm which pass through them. They can be placed in exhaustion ducts, in room ceilings or in movable filtration units. The use of HEPA filters and/or UV light is strongly recommended for rooms where the following procedures take place: bronchoscopy, induced sputum, pentamidine nebulization, necropsy, and isolation. The combination of an adequate number of air changes with negative pressure and a HEPA filter or UV light minimizes the risk of transmission in the environment in which the TB patient is assisted and in the area where the air is exhausted. The germicidal efficiency of the UV light is limited to its area of direct incidence and decreases with time. HEPA filters are used: · To purify the exhaustion of air of contaminated environments · To recirculate the air inside the room or to other rooms facilitating the number of air changes per hour. Basic engineering recommendations In areas with a high risk of infection, the main engineering measure is to facilitate ventilation so that the particles suspended in the air are removed at the highest speed possible. The speed of air removal is calculated in air changes per hour and should be: · six air changes per hour for the isolation, the ambulatory, the X-ray, the waiting and the emergency rooms, and the ventilatory assistance areas · twelve air changes per hour for the bronchoscopy, the sputum induction, the pentamidine nebulization and the autopsy rooms and the mycobacteria laboratory The use of negative pressure Negative pressure prevents the dispersion of contaminated air into areas where people walk, mainly those in common use such as corridors. The exhaust air should never be directed towards these transit areas. If safe air exhaustion is not possible, the exhausted air should be filtered or sterilized. Respiratory isolation room The isolation room must: · Be private and with suitable ventilation characteristics · Be under negative pressure · Be submitted to six or more air changes per hour · Have air exhaustion to the open-air · Have HEPA filters if the air is recirculated or exhausted to circulation areas · Have anterooms (they increase isolation effectiveness, minimizing the escape risk) · Have UV light (optional) · Be submitted to six air changes between a patient’s discharge and the following patient’s admission Outpatient clinic In areas dedicated to ambulatory care, the minimum biosecurity conditions should include: · Adequate (ventilated and sunny) site for sputum collection, preferentially outdoors · Air flow adaptation of the waiting and consultation rooms, avoiding the use of ceiling fans; air conditioning is allowed only in combination with HEPA filters · Suitable area for the waiting room, preferably outdoors, far away from any crowded area or other waiting rooms · Within the assistance room, use of a standing fan either to direct the air flow towards the window (or door) or to produce an air “barrier” between the doctor and the patient · The use of standing fans and exhaust fans in strategic points is a low-cost alternative to increase the number of air changes per hour · Adaptation to the environment to which the air is being directed, avoiding other people being exposed to the risk of infection 220.127.116.11. Individual Protection Measures for healthcare personnel at risk · Masks: they can be of the N-95 type, with a National Institute for Occupational Safety and Health (NIOSH) certification of the United States (US) or of the PFF-2 type, with international standards certification; common surgical masks are not advisable: their effectiveness in preventing the inhalation of particles with diameters of 1 to 5 µm is less than 50 % (they were specifically designed to prevent the exhalation of particles) · The protection masks should be supplied by the health service where the TB patients are assisted, preferably in various sizes and models · Even if administrative and environmental control measures are in force, healthcare workers should wear appropriate respiratory protection devices (N95 or PFF2) at all times while they are in patients’ rooms, during bronchoscopy, induced sputum, pentamidine nebulization, surgery or autopsy performed on suspected or confirmed TB cases · Instruct the personnel on the correct use of the special masks, reminding male employees that they should have their faces shaved as beards and/or mustaches can prevent perfect adjustment of the mask to the face · Special masks (N95 or PFF2 respirators) can be used for indeterminate periods of time, as long as they are kept dry, clean and intact (without any torn, frayed or crumpled areas); their storage in plastic bags after use must be avoided because bags retain humidity For TB patients transiting through the institution · Indicate the use of common surgical masks for the respiratory symptomatic patients as soon as they enter the unit (triage, emergency, ambulatory, when being admitted or when passing through). The surgical masks work as a barrier, capturing the damp particles (usually larger than 5 µm) and, therefore, do not work as filters. · In the day-hospital sector, HIV-negative patients who have been coughing for more than three weeks should wear a common mask all the time whilst there; HIV/AIDS patients with any respiratory symptom should use a common mask all the time. When the engineering measures are not working in the room, the asymptomatic patient in the same setting should be instructed to use a special mask (N95 or PFF2), particularly if immunosuppressed. 11.1.5. Tuberculin skin test survey The evaluation of the risk of infection from M. tuberculosis (through tuberculin investigation) should be performed on healthcare personnel in the following situations: · Recently admitted personnel · Personnel that report frequent contact with pulmonary TB patient It is important that every health unit knows the prevalence of TB infection and TB disease among the healthcare personnel. In this sense, the healthcare worker that reports a past history of active TB or household contact with a pulmonary TB case in the last two years must be submitted to medical examination, tuberculin testing and a chest X-ray. A tuberculin skin test (TST) should be applied and read by one of a limited-number of trained nurses tested for intra- and inter-reader variability. Tuberculin purified protein derivative (PPD) will be injected subcutaneously and the amount of induration should be measured at 48-72 hours. For healthcare workers with an induration < 10 mm, the tuberculin skin test should be repeated 7-10 days later. Those with a two-step tuberculin skin test < 10 mm should be asked to undergo a repeated tuberculin skin test 6-12 months later. Those with a tuberculin skin test = 10 mm and those who experienced a tuberculin skin test conversion should undergo a medical evaluation to rule out TB disease. Since 1995, bacille Calmette-Guérin (BCG) revaccination has not been recommended by the WHO. Few countries still maintain the use of BCG revaccination. Recently, in an open, randomized clinical trial performed in Brazilian children, it was found that a second BCG vaccination at school age has low effectiveness. Because of these results and those described in the international literature, BCG vaccination is no longer recommended for healthcare personnel in some countries, including Brazil (Rodrigues 2005). According to a study performed in the US, tuberculin investigation every 12 months in areas with a high risk of TB infection would be more cost-effective than other measures for preventing TB. Chemoprophylaxis should be indicated to recent PPD converters (induration increase of 10 mm in relation to the last test) (Nettleman 1997). 11.1.6. Recommendations Flaws related to biosecurity measures (administrative, environmental or of individual protection) are factors known to be associated with higher nosocomial TB transmission. The primary tuberculous infection may manifest itself as a light respiratory condition with hardly any clinical or radiological signs. Consequently, it usually remains undiagnosed. During this process, M. tuberculosis spreads both lymphatically and hematogenously and the bacilli implanted in extrapulmonary organs or tissues are a potential source of subsequent reactivation. Generally, the tuberculin skin test is the sole indication that M. tuberculosis infection has occurred. It is estimated that 10 % of individuals infected with M. tuberculosis will develop active TB at some time during their lifetime. The risk of becoming sick with TB is highest in the first two years after the infection, when about 5 % of infected individuals undergo a progression from latent to active disease. The other 5 % can develop active TB at any time in their lifetime if they do not receive the treatment recommended for latent infection. Even in places where TB is endemic and BCG vaccination is universal, the result of the tuberculin skin test reflects, with reasonable accuracy, exposure to M. tuberculosis. In countries with a high prevalence of TB, in which 25 to 50 % of the population is considered to be infected by M. tuberculosis, the tuberculin skin test is highly specific and a positive result has a high probability of indicating tuberculous infection. The adequate establishment and fulfillment of TB biosafety measures are the tools needed to reach the goal of reducing the annual risk of infection in healthcare personnel to levels similar to those of the general population. 11.2. Biosafety in the laboratory 11.2.1. Introduction Microbiology laboratories are unique and special work environments, where the handling of infectious organisms may pose risks of infection to the laboratory personnel or the surrounding community. Several cases of infections acquired in the laboratory have been reported throughout the history of microbiology. By the end of the 19th century and the beginning of the 20th, reports had already been published describing laboratory-associated cases of typhoid, cholera, brucellosis, and tetanus. By the middle of the 20th century, a few publications reported cases of laboratory-related infections in the United States. Some of these cases were attributed to carelessness or inappropriate techniques in the handling of infectious material (Meyer 1941, Sulkin 1949, Sulkin 1951). A laboratory survey was updated in 1976 (Pike 1976) totaling 3,921 cases. Brucellosis, typhoid, tularemia, TB, hepatitis and Venezuelan equine encephalitis accounted for most of the infections. Not more than 20 % of these cases were associated with a documented accident. Exposure to infectious aerosols was considered to be a likely but unconfirmed source of infection in more than 80 % of the reported cases, in which the infected person had “worked with the agent”. Pike, in 1979, concluded that “the knowledge, the techniques and the equipment to prevent most laboratory infection were available” (Pike 1979). The actual risk of a laboratory-acquired infection is difficult to measure because there is no systematic reporting system. Besides, surveillance data on laboratory-associated infections are difficult to collect because the infections are often subclinical and have an atypical incubation period and route of infection. Another problem is that laboratory directors may not report incidents for fear of reprisal or embarrassment (Sewell 1995). The risk of exposure to infectious agents tends to be lower for laboratory workers than other groups of healthcare workers. However, the risk of laboratory-associated infection in employees of clinical and research laboratories is greater than that of the general population, suggesting that unique risks are associated with the laboratory work environment (Kiley 1992). The advent of the HIV/AIDS epidemic in the early ’80s and the fact that the rate of new cases of TB began to rise in 1986 in developed countries (Tenover 1993), put laboratory safety and safety programs in the spotlight. The safety concerns led to the elaboration of guidelines and manuals (Centers for Disease Control 1987, Occupational Safety and Health Administration 1991). A decrease in the occupational risks associated with working in a clinic or laboratory was observed after these guidelines were adopted (Fahey 1991, Wong 1991). The term “containment” is used when describing safe methods for managing infectious material in the laboratory environment where they are handled or stored. The purpose of containment is to reduce or eliminate exposure of laboratory workers, other people, and the outside environment to potentially hazardous agents. Primary containment: protection of laboratory workers and the immediate laboratory environment from exposure to infectious agents is provided by both good microbiological technique and the use of appropriate safety equipment. The use of vaccines may provide an increase in the level of personal protection. Secondary containment: protection of the environment outside the laboratory from exposure to infectious materials is provided by a combination of facility design and operational practices. Therefore, the three elements of containment include laboratory practice and technique, safety equipment, and facility design. The risk assessment of the work to be done with a specific agent will determine the appropriate combination of these elements (Blumberg 2000, Blumberg 2004, Centers for Disease Control and Prevention 1994, Centers for Disease Control and Prevention 2005). The most important element of containment is the strict adherence to standard microbiological practices and techniques. People who work with infectious agents or potentially infected materials must be aware of potential hazards and must be trained and proficient in the practices required for the safe handling of these materials. The director of the laboratory is also responsible for providing or arranging the appropriate training of personnel. Each laboratory should develop or adopt a biosafety manual or operations manual that identifies the hazards that are or may be found in the laboratory, and that specifies practices and specific procedures designed to minimize or eliminate the exposure to such hazards. Personnel should be informed about the special hazards and should follow the necessary practices and procedures. A scientist trained and knowledgeable in appropriate laboratory techniques, safety procedures and hazards associated with the handling of infectious agents must be responsible for the conduct of work with any infectious agent or infected material. M. tuberculosis is repeatedly ranked within the top-five most common laboratory-acquired infections (Collins 1998, Miller 1987, Sepkowitz 1994, Seidler 2005). Pike reported that laboratory and mortuary workers exposed to tubercle material have a TB incidence rate three times higher than that of the general population and indicated that only 18 % of infections could be traced back to a known event (Pike 1976). Despite the current knowledge and biosafety measures in place, a recent report in New York demonstrated rates from 2 to 6.6 % of TB conversion among healthcare workers (Garber 2003). In addition, surveys suggest that the actual incidence of laboratory-acquired infections due to M. tuberculosis is greater than the number of reported cases. The documentation of a case of laboratory-acquired TB is difficult because the source of the infection is often unclear, as a result of the potential for exposure outside of the workplace and the long incubation period before the development of symptomatic disease (Collins 1993, Pike 1979). The incidence of TB in laboratory personnel is estimated to be three to nine times that of individuals in other job environments (Harrington 1976, Reid 1957, Saint-Paul 1972). Manipulation of specimens or cultures that generate aerosols is the most important risk factor for acquiring TB in the laboratory. Aerosolization occurs frequently during autopsies, preparation of frozen sections of infected tissues, and procedures involving liquid cultures (Centers for Disease Control and Prevention 1981, US Department of Health and Human Services 1993). M. tuberculosis presents a low infective dose for humans of less than 10 bacilli (Riley 1957, Riley 1961), suggesting a high risk for laboratory-acquired infection. Due to the nature of this organism, containment level 3 (CL3) laboratory operational and physical requirements have been recommended for manipulation of the live organism in North America (US Department of Health and Human Services 1995). Therefore, one would hypothesize that working in a CL3 with personal protective equipment, including a respirator, would be adequate to protect the worker. However, as tuberculin skin test conversion is still occurring (Blackwood, 2005), other practices and causes should be analyzed. These recommended measures are implemented by healthcare facilities in high-income countries, but given their high cost, few facilities in low-income countries can afford to implement them (Pai 2006). The WHO has proposed practical and low-cost interventions to reduce nosocomial transmissions in settings where resources are limited, and these are available on the internet at http://www.who.int/docstore/gtb/publications/healthcare/index.htm (World Health Organization 1999). Several simple interventions can ameliorate working conditions, such as training and supervising laboratory workers in good techniques and biosafety practices to provide the necessary organization (DeRiemer 2000, Joshi 2006). 11.2.2. Laboratory biosafety levels Infectious microorganisms are classified by risk group. This type of classification is to be used for laboratory work purposes only. · Risk Group 1 (no or low individual and community risk) A microorganism that is unlikely to cause human or animal disease. · Risk Group 2 (moderate individual risk, low community risk) A pathogen that can cause human or animal disease, but is unlikely to be a serious hazard to laboratory workers, the community, livestock or the environment. Laboratory exposure may cause serious infection, but effective treatment and preventive measures are available and the risk of spread of infection is limited. · Risk Group 3 (high individual risk, low community risk) A pathogen that usually causes serious human or animal disease but does not ordinarily spread from one infected individual to another. Effective treatment and preventive measures are available. · Risk Group 4 (high individual and community risk) A pathogen that usually causes serious human or animal disease and that can be readily transmitted from one individual to another, directly or indirectly. Effective treatment and preventive measures are not usually available. Biosafety Level designations: are based on a combination of the design features, construction, containment facilities, equipment, practices and operational procedures required for working with agents belonging to the various risk groups (World Health Organization 2004). Laboratory facilities are designated as: · Biosafety Level 1 – basic laboratory · Biosafety Level 2 – basic laboratory · Biosafety Level 3 – laboratory with containment conditions · Biosafety Level 4 – laboratory with maximum containment A national classification of microorganisms, by risk group, may be determined taking into account regional characteristics: · Organism: pathogenicity, mode of transmission · Host: immunity, density vectors, environment · Preventive measures · Treatment 11.2.3. Risk assessment Any laboratory work should be done under appropriate biosafety conditions based on risk assessment. Such an assessment will take into considerations the agent risk group as well as other factors to establish the biosafety level (World Health Organization 2004). Organism Factors that should be considered concernin