Variola Virus
Variola Virus
PATHOGEN SAFETY DATA SHEET – INFECTIOUS SUBSTANCES
SECTION I – INFECTIOUS AGENT
NAME: Variola virus(1,2).
SYNONYM OR CROSS REFERENCE: Smallpox, VARV, and variola minor virus strains (alastrim, amass, or kaffir viruses)(1,2,3).
CHARACTERISTICS: A member of the family Poxviridae , subfamily Chordopoxvirinae , genus Orthopoxvirus . Virions are shaped like bricks on electron micrographs and measure approximately 300 x 250 x 200 nm(2,4). Orthopoxviruses have an outside envelope and a second membrane underneath. Instead of a capsid, poxviruses have a nucleosome which contains DNA, and is surrounded by its own membrane(5). They contain single, linear, double-stranded DNA molecules of 130 to 375 kb pairs and replicate in the cell cytoplasm(4). Variola virus is the most complex of the orthopoxvirus genus, having many different strains(6,7).
SECTION II – HAZARD IDENTIFICATION
PATHOGENICITY/TOXICITY: Smallpox is an acute, contagious disease with two main forms, variola major and variola minor, both of which cause similar lesions(1). There are 4 types of variola major infection presentations.
Ordinary variola major : The most common form, which accounts for more than 90% of cases and has a fatality rate of approximately 30% among unvaccinated individuals, and 3% for vaccinated individuals(8). The cause of death is usually bronchopneumonia, although in about 3% of cases, fatal haemorrhages occur. The prodromal phase consists of sudden onset of influenza-like symptoms, characterized by fever, malaise, headache, prostration, severe back pain, and sometimes abdominal pain and vomiting. Two to 3 days later, the temperature falls and the patient feels somewhat better, at which time a characteristic rash appears, first on the face (starting as small red spots) then on the tongue, mouth, nose, and hands. After a few days, the rash progresses to the trunk where fewer lesions occur. Lesions in the mucous membranes of the nose and mouth ulcerate quickly, releasing large amounts of virus into the mouth and throat. Lesions progress from macules to papules to vesicles to pustules, and at 8 to14 days, the pustules form scabs which leave depressed depigmented scars upon healing. All lesions in a given area progress through these stages together(1,8).
The milder or “modified” variola major : Accounts for 2% of cases in unvaccinated persons and for 25% in previously vaccinated persons. Cases are rarely fatal with fewer, smaller, and more superficial lesions than those in patients with the ordinary type(4).
Haemorrhagic variola major : A rare form of variola major which is always fatal and involves haemorrhages in the mucous membranes and the skin(1,4).
Flat variola major : Another rare form of variola major that is almost always fatal and is characterized by lesions that do not develop to the pustular stage, but remain soft and flat(2,4).
Variola minor : The other main form of smallpox (also known as alastrim), which is a milder illness with a fatality rate of less than 1%(1).
Another type of smallpox, variola sine eruptione , occurs in previously vaccinated contacts or in infants with maternal antibodies. Affected persons are asymptomatic or have a brief rise in temperature, headache, and present influenza-like symptoms. The transmission of clinical smallpox has not been documented with variola sine eruptione(4). Overall, 65% to 80% of smallpox survivors have pockmarks, mostly on the face(1).
EPIDEMIOLOGY: As a result of a successful worldwide vaccination program, smallpox was eradicated, with the last natural infection occurring in Somalia in 1977(1,8).
HOST RANGE: Humans(1). Monkeys are also susceptible to infection(8).
INFECTIOUS DOSE: Viruses in an aerosol suspension can spread widely, and infect at a very low dose (10 to 100 organisms)(8,9,10).
MODE OF TRANSMISSION: Transmission occurs via respiratory droplets (primary route of transmission), or via fine-particle aerosol, or skin inoculation. The conjunctiva or placenta may be occasional portals of entry(1). Respiratory droplets (i.e., coughing, sputum, and saliva) have a range of likely no more than 2 metres and are, therefore, a threat only to persons in the immediate vicinity of the affected patient(11).
INCUBATION PERIOD: Can range from 7-19 days(12). Typically, onset of illness occurs after 10-14 days and 2-4 more days for onset of rash to occur(4,9,12).
COMMUNICABILITY: The highest risk of transmission is during the appearance of the earliest lesions; however, the period of communicability is from the development of the earliest lesions to the disappearance of all scabs (about a 3 week period)(1). Some infected people shed the virus without ever showing signs of illness(5).
SECTION III – DISSEMINATION
RESERVOIR: No known animal or environmental reservoir. Currently, the virus isolates are maintained only in World Health Organization (WHO) designated laboratories(1).
ZOONOSIS: None.
VECTORS: None.
SECTION IV – STABILITY AND VIABILITY
DRUG SUSCEPTIBILITY: The acyclic nucleoside phosphonate analogue cidofovir has been shown to have activity against variola virus in cell culture, and in animal models, including animals where therapy was delayed until the first signs of smallpox(13,14).
SUSCEPTIBILITY TO DISINFECTANTS: Inactivation can be achieved using apolar lipophilic solvents (chloroform) and quaternary ammonia compounds(15). Other disinfectants used for standard hospital infection control such as 0.5% or 200 ppm hypochlorite, 40% ethanol, 30% isopropyl alcohol, formalin, formaldehyde, phenol, cresol, surface-active detergents (e.g. 100 ppm benzalkonium chloride), chlorobenzene mixtures, and 75 ppm iodophor may be effective(15,16,17,18,19).
PHYSICAL INACTIVATION: Inactivated by heat (incineration and autoclaving)(18).
SURVIVAL OUTSIDE HOST: The virus can be propagated in a monkey kidney cell line(17). Specimens of blood, scrapings from skin lesions, saliva, pustular fluid, and crusts can be transported and stored for short periods without refrigeration. Materials from smallpox patients (dried fluid and crusts) containing virus remain infectious at room temperature for approximately 1 year. The infectivity of the virus is maintained at 4°C for several months and at -20 to -70°C for years(15). Based on the behaviour of vaccinia virus, it is believed that aerosolized variola can retain its infectivity for up to 24 hours if not exposed to UV light, and if temperatures are cool (10°C to 11°C) and humidity low (20%). Variola can be almost completely destroyed within 6 hours in an atmosphere of high temperature (31°C to 33°C) and humidity (80%). At cooler temperatures (26°C), variola virus has survived for 8 weeks at high relative humidity and 12 weeks at a relative humidity less than 10%. Virus has been isolated from scabs that had been sitting on a shelf for 13 years(9). It was also found to be viable in bread, salad, sausages and gauze bandages stored at 4°C for up to 2 weeks, and in storm water kept at 4.5 °C for up to 166 days(5). Samples of freeze-dried virus in a laboratory have been revived after storage for 20 years(20).
SECTION V – FIRST AID / MEDICAL
SURVEILLANCE: In the past, smallpox was sometimes confused with chickenpox. The centrifugal distribution of lesions, mostly on the face and extremities than on the trunk, is a distinctive diagnostic feature of smallpox which serves to distinguish it from chickenpox, which is characterized by much more superficial lesions that are concentrated mostly on the trunk, as opposed to the face and extremities(1,8).
There are several methods for confirming the diagnosis. Some are specific for variola virus, and others are for orthopoxviruses in general. Haemadsorption with susceptible chicken erythrocytes is an early detection method for infection with smallpox virus. Giemsa-stained smears of material from skin lesions may show Guarnieri inclusion bodies. The soluble antigens in blood, vesicle fluid, pustule fluid, and saline extracts from crusts or scrapings in certain stages of disease can be detected via complement fixation, haemagglutination inhibition, immunofluorescence, and Ouchterlony techniques. Serologic response is variable in partially immune patients, who may present clinically with variola sine eruptione(15). Specimens such as vesicular or pustular fluids or scabs can be examined directly for the presence of virions by electron microscopy, and viral antigen can be identified by immunohistochemical studies. Isolation of the virus in live-cell cultures, followed by PCR, or growth on chorioallantois, is confirmatory; however, PCR diagnostic techniques are more accurate(4). The results of serologic testing do not differentiate among orthopoxvirus species, and paired serum samples are required to distinguish recent infection from vaccination in the remote past. Newer methods, that detect IgM responses, may enhance the sensitivity and specificity of serological test(4). Other diagnostic methods such as immunodiffusion technique, ELISA, restriction fragment-length polymorphisms, and in situ hybridization have been suggested by various laboratories for confirming the presence of Variola(1,8,9,21).
Note: All diagnostic methods are not necessarily available in all countries.
FIRST AID/TREATMENT: If possible, a suspected case of smallpox should be managed in a negative-pressured room, and the patient should be vaccinated, particularly in an early stage of illness. Strict respiratory and contact isolation is imperative. When there are many patients, an isolation hospital or other facility should be designated. Penicillinase-resistance antimicrobial agents should be used if smallpox lesions are secondarily infected, if bacterial infection endangers the eyes, or if the eruption is very dense and widespread. Daily eye rinsing is required in severe cases. Patients need adequate hydration and nutrition. Topical idoxuridine should be considered for the treatment of corneal lesions, although its efficacy is unproved for smallpox(4,15). Leukocyte transfer from immuno-compromised persons, and methisazone have been used to treat Vaccinia gangrenosa (or progressive vaccinia), which is characterized by a slowly progressive enlargement and necrosis or gangrene of the skin at the site of smallpox vaccination that can be fatal if treated with non-specific measures only (antibiotics or steroids alone)(22).
IMMUNIZATION: The vaccine consists of a live Vaccinia virus , which is a “pox”-type virus related to smallpox. There are significant side effects and risks associated with this vaccine, such as skin complications (eczema vaccinatum) which may occur in people with pre-existing eczema, allergic reactions at site of vaccination, vaccinia gangrenosa (or progressive vaccinia), eye infections (spread of virus from site of vaccination), postvaccinal encephalitis, intrauterine vaccinia, and viremia(15). Thus vaccination should be administered only to those exposed to the virus or facing a high probability of exposure(4). A successful primary vaccination confers full immunity to smallpox in more than 95% of persons for perhaps 5 to 10 years, and successful revaccination probably provides protection for 10 to 20 years or more(4,23).
The recently recognised risk of myopericarditis with both first and second generation vaccinia vaccines serves as a reminder that larger-scale studies of newer vaccines are necessary to further define their safety profiles and relative roles in protection against smallpox(24). Two attenuated vaccine strains have also been isolated and tested: modified vaccinia Ankara (MVA), which has been effectively used in more than 1900 people with few adverse effects(25); and a Japanese strain (LC16m8), which is licensed in Japan, and was safely used on more than 50,000 children in the 1970(26).
PROPHYLAXIS: Vaccination very early in the incubation period (within 3 to 4 days of exposure) can markedly attenuate or even prevent clinical manifestations of smallpox. Full protection occurs after successful vaccination(4). Vaccination at 4 to 7 days after exposure likely offers some protection from disease or may modify the severity of disease(23). Unless directly exposed, the vaccine is not advised for groups of people at greater risk for serious side effects, including pregnant and nursing women, children younger than 12 months of age, immuno-compromised patients, HIV patients, or patients with a history of eczema(4,23). Vaccinia immune globulin has also been administered (0.6 ml/kg IM) within 3 days of exposure(4,10).
SECTION VI – LABORATORY HAZARDS
LABORATORY-ACQUIRED INFECTIONS: Except for a laboratory-associated smallpox death at the University of Birmingham, England, in 1978, no further cases have been identified. All known variola virus stocks are held under security at WHO collaborating centers located at Centers for Disease Control and Prevention, Atlanta, United States, or the State Research Centre of Virology and Biotechnology, Koltsovo, Novosibirsk Region, Russia(1,4). The possession and use of variola viruses are restricted to the WHO collaborating centers(27).
SOURCES/SPECIMENS: Scrapings of skin lesions, scab materials, papular, vesicular, or pustular fluid, crusts, bodily fluids including blood and urine, respiratory secretions, pharyngeal and tonsillar swabbings(1,4,8,19,27).
PRIMARY HAZARDS: Ingestion, parenteral inoculation, and droplet or aerosol exposure of mucous membranes or broken skin with infectious fluids or tissues(27).
SPECIAL HAZARDS: Genetically engineered recombinant vaccinia viruses pose a potential risk to laboratory personnel, through direct contact or contact with clinical materials from infected volunteers or animals(8,27).
SECTION VII – EXPOSURE CONTROLS / PERSONAL PROTECTION
RISK GROUP CLASSIFICATION: Risk Group 4(28).
CONTAINMENT REQUIREMENTS: Containment Level 4 facilities, equipment, and operational practices for work involving infectious or potentially infectious materials, animals, or cultures.
PROTECTIVE CLOTHING: Personnel entering the laboratory must remove street clothing, including undergarments, and jewellery, and change into dedicated laboratory clothing and shoes, or don full coverage protective clothing (i.e., completely covering all street clothing). Additional protection may be worn over laboratory clothing when infectious materials are directly handled, such as solid-front gowns with tight fitting wrists, gloves, and respiratory protection. Eye protection must be used where there is a known or potential risk of exposure to splashes(29).
OTHER PRECAUTIONS: All activities with infectious material should be conducted in a biological safety cabinet (BSC) in combination with a positive pressure suit, or within a class III BSC line. Centrifugation of infected materials must be carried out in closed containers placed in sealed safety cups, or in rotors that are loaded or unloaded in a biological safety cabinet. The integrity of positive pressure suits must be routinely checked for leaks. The use of needles, syringes, and other sharp objects should be strictly limited. Open wounds, cuts, scratches, and grazes should be covered with waterproof dressings. Additional precautions should be considered with work involving animal activities(29).
SECTION VIII – HANDLING AND STORAGE
SPILLS: Allow aerosols to settle and, wearing protective clothing, gently cover spill with paper towels and apply appropriate disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time before clean up (30 min)(29).
DISPOSAL: Decontaminate all materials for disposal by steam sterilisation, chemical disinfection, and/or incineration(29).
STORAGE: In leak-proof containers that are appropriately labelled and locked in a Containment Level 4 laboratory(29).
SECTION IX – REGULATORY AND OTHER INFORMATION
REGULATORY INFORMATION: The import, transport, and use of pathogens in Canada is regulated under many regulatory bodies, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment Canada, and Transport Canada. Users are responsible for ensuring they are compliant with all relevant acts, regulations, guidelines, and standards.
UPDATED: September 2010.
PREPARED BY: Pathogen Regulation Directorate, Public Health Agency of Canada.
Although the information, opinions and recommendations contained in this Pathogen Safety Data Sheet are compiled from sources believed to be reliable, we accept no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information. Newly discovered hazards are frequent and this information may not be completely up to date.
Copyright © Public Health Agency of Canada, 2010 Canada
This MSDS / PSDS document, provided by Public Health Agency of Canada (PHAC), is offered here as a FREE public service to visitors of MSDSonline. As outlined in this site’s Terms of Use, MSDSonline is not responsible for the accuracy, content or any aspect of the information contained therein.
Trichomonas vaginalis
PATHOGEN SAFETY DATA SHEET – INFECTIOUS SUBSTANCES
SECTION I – INFECTIOUS AGENT
NAME: Trichomonas vaginalis
SYNONYM OR CROSS REFERENCE: Trichomoniasis, vaginitis.
CHARACTERISTICS: Trichomonas vaginalis is a parasitic protozoan flagellate, and organisms vary in size but are usually around 10 μm in length and 7 μm in width(1,2). It usually has an oval or pear-like shape, but can assume an amoeboid form when attached to vaginal epithelial cells. T. vaginalis has a total of 5 flagella, four of which are located at its anterior portion. The fifth flagellum is incorporated within the undulating membrane(1,3). The anaerobic parasite can only exist as a trophozoite and lacks a cystic stage, reproducing by longitudinal binary fission. Growth is optimized at 37°C at pH 6.0 – 6.3, but can survive at up to pH 7(4).
SECTION II – HAZARD IDENTIFICATION
PATHOGENICITY/TOXICITY: T. vaginalis is generally restricted to the genitourinary tract by the host’s immune system, and is the etiological agent of human trichomoniasis(2). Infection has been associated with an increased risk of human immunodeficiency syndrome in both sexes(4).
In women: Symptoms of infection include vaginal secretion that is scanty and mixed with mucus; malodorous discharge that is frothy, yellow or green, mycopurulent, and copious(4). The protozoan can be found in the vagina, cervix, bladder, Bartholin’s, Skene’s, and periurethral glands. Complications may result in cervical erosion, cervical cancer, infertility, adnexitis, pyosalpinx, and endometritis. Premature rupture of the placental membranes can occur in pregnant women, resulting in premature birth and low-birth weight(5). Acute infections are characterised by severe pruritus, vaginitis, vulvitis with dysuria and dyspareunia, and hemorrhagic spots on the mucosa (in 2% of patients) which results in colpitis macularis or petechiae (strawberry cervix). In females, 50% of cases are asymptomatic. Infection can persist for long periods of time in the urogenital tract of women. 25 – 50% are asymptomatic for the first 6 months of infection, and organisms can survive indefinitely in the lower urogenital tract if left untreated(1,6).
In men: Prevalence is lower in men, and infection is often asymptomatic(7). Infection in men can be present in the prostate, seminal vesicles, and epididymis. Complications are rare, but can potentially lead to genitourinary inflammation disease, sterility, scanty, clear to mucopurulent discharge, dysuria, non-gonococcal urethritis, prostatitis, balanoposthitis, epididymitis, and urethral disease(4). Infection is usually mild with no symptoms, thus making men potential carriers. Spontaneous resolution of infection is common as the oxidative nature of the male genital tract is speculated to be inhibitory to pathogenic factors of infection, which usually remains for 10 days or less(1).
EPIDEMIOLOGY: Worldwide – trichomoniasis caused by T. vaginalis is one of the most common non-viral sexually transmitted diseases with an estimated 170 million cases occurring annually (no seasonal variability)(1), and incidence has been found to be high in non-hispanic black women(5). Infection usually occurs in women during reproductive years, and occurrence before menarche or after menopause is rare(4). Fourteen to 60% of male infections are associated with known infected female partners(1).
HOST RANGE: Humans(1).
INFECTIOUS DOSE: Experimental studies have shown that urogenital inoculation with 10,000 to 120,000 organisms has resulted in transmission, although epidemiological examinations have shown that the infective dose in women is low and the infection rate is high(8-10).
MODE OF TRANSMISSION: Commonly spread through sexual contact with vaginal or urethral discharges of infected persons(1), and transmission of organisms via artificial insemination of infected cryobanked semen is also possible(11). Non-sexual transmission is rare but has been observed in cases involving contaminated douche nozzles, moist wash-clothes, specula, or toilet seats(1,12,13). Transmission to newborn infants from infected mothers is possible and is observed in 2 – 17% of cases, and can result in urinary tract or vaginal infections(1).
INCUBATION PERIOD: Ranges from 3 – 28 days with an average of 7 days(4,14).
COMMUNICABILITY: Infection can persist for a significant period of time in asymptomatic cases(14), from months to years. SECTION III – DISSEMINATION
RESERVOIR: Humans, typically females, while men may act as a reservoir for infection(4).
ZOONOSIS: None.
VECTORS: None.
SECTION IV – STABILITY AND VIABILITY
DRUG SUSCEPTIBILITY: The only drugs that have been approved by the FDA for use in the United States are metronidazole (although the use of this drug can increase the incidence of preterm birth)(15), and Tinidazole (trade name known as Tindamax)(16). Ornidazole, secnidazole, and nimorazole can be used in countries outside of the US. In vitro testing has shown that nitroimidazole EU11100 also has similar efficacy as metronidazole(15).
DRUG RESISTANCE: Studies have shown that at least 5% of clinical cases of trichomoniasis are caused by metronidazole-resistant T. vaginalis, and cross-resistance to tinidazole is a concern as the two drugs are similar in modes of action (4).
SUSCEPTIBILITY TO DISINFECTANTS: Susceptible to 1% sodium hypochlorite, and 70% ethanol(17).
PHYSICAL INACTIVATION: Inactivated below pH 5(4). Organisms cannot survive long (several hours) in dry conditions(1).
SURVIVAL OUTSIDE HOST: The organism grows best at 37°C, and specimens in urine should be considered viable for only 30 minutes to avoid false negatives (2 hours if PCR is used)(18). Live T. vaginalis have been found in swimming pool water, in urine, and semen after up to 6 – 24 hours, and up to 30 – 45 minutes when exposed to air(1,19,20). Studies have also shown that T. vaginalis organisms are able to survive through the cryopreservation process of human semen, making infection via artificial insemination possible(11).
SECTION V – FIRST AID / MEDICAL
SURVEILLANCE: Monitor for symptoms. Current laboratory diagnoses include direct microscopic observation, cell culture, immunological techniques, PCR assay, nucleic acid probe test, immunochromatographic capillary-flow dipstick technology, DNA probing and gene amplification, and in situ hybridization(2,9,16).
Note: All diagnostic methods are not necessarily available in all countries.
FIRST AID/TREATMENT: Topical vaginal medications and pessaries (such as clotrimazole, povidone-iodine, nonoxynol-9, and arsenical pessaries) may be prescribed for treatment in women to lessen the effects of symptoms; however, these do not consistently cure disease(4). Topical paromycin has been found to be effective, but side effects can be mild to severe(21). There are no topical medications available for men. Metronidazole can be administered orally or intravenously, with cure rates of 85-95%(1); Metronidazole should not be used by pregnant women in their first trimester as it has been linked to higher prevalence of preterm birth(22).
IMMUNISATION: No vaccinations are currently available. Two vaccines have progressed to the human clinical trials stage in the past 50 years (a heat-killed T. vaginalis vaccine, and SolcoTriovac), although they have not been proven to be effective against T. vaginalis(4).
PROPHYLAXIS: Since many males are asymptomatic and may be carriers, it is important to concurrently treat male partners of infected women to prevent re-infection(4).
SECTION VI – LABORATORY HAZARDS
LABORATORY-ACQUIRED INFECTIONS: None reported to date.
SOURCES/SPECIMENS: Vaginal and urethral secretions, urine, human semen(4,11,18).
PRIMARY HAZARDS: Droplet exposure to mucous membrane, accidental parenteral inoculation and sexual transmission(1,23).
SPECIAL HAZARDS: None.
SECTION VII – EXPOSURE CONTROLS / PERSONAL PROTECTION
RISK GROUP CLASSIFICATION: Risk Group 2(24).
CONTAINMENT REQUIREMENTS: Containment Level 2 facilities, equipment, and operational practices for work involving infected or potentially infected materials, animals, or cultures.
PROTECTIVE CLOTHING: Lab coat. Gloves when direct skin contact with infected materials or animals is unavoidable. Eye protection must be used where there is a known or potential risk of exposure to splashes(25).
OTHER PRECAUTIONS: All procedures that may produce aerosols, or involve high concentrations or large volumes should be conducted in a biological safety cabinet (BSC). The use of needles, syringes, and other sharp objects should be strictly limited. Additional precautions should be considered with work involving animals or large scale activities(25).
SECTION VIII – HANDLING AND STORAGE
SPILLS: Allow aerosols to settle and, while wearing protective clothing, cover spill with absorbent paper towel. Apply appropriate disinfectant, and starting from perimeter and wipe towards the center. Allow sufficient contact time with the disinfectant before cleaning up.
DISPOSAL: Decontaminate all wastes that contain or have come in contact with the infectious organism before disposing by autoclave, chemical disinfection, gamma irradiation, or incineration(25).
STORAGE: Properly labelled and sealed containers.
SECTION IX – REGULATORY AND OTHER INFORMATION
REGULATORY INFORMATION: The import, transport, and use of pathogens in Canada is regulated under many regulatory bodies, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment Canada, and Transport Canada. Users are responsible for ensuring they are compliant with all relevant acts, regulations, guidelines, and standards.
UPDATED: November 2010
PREPARED BY: Pathogen Regulation Directorate, Public Health Agency of Canada
Although the information, opinions and recommendations contained in this Pathogen Safety Data Sheet are compiled from sources believed to be reliable, we accept no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information. Newly discovered hazards are frequent and this information may not be completely up to date.
Copyright © Public Health Agency of Canada, 2010 Canada
This MSDS / PSDS document, provided by Public Health Agency of Canada (PHAC), is offered here as a FREE public service to visitors of www.EHS.com. As outlined in this site’s Terms of Use, VelocityEHS is not responsible for the accuracy, content or any aspect of the information contained therein.
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