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• Associate Director of Cancer Research Pathology, Sidney Kimmel Comprehensive Cancer Center
• Professor of Pathology

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This nding was consistent across regions bipolar depression episodes generic 50 mg anafranil with visa, in different ethnic groups mood disorder 10 purchase anafranil once a day, and in men and women (247) anxiety 12 step groups effective anafranil 25 mg. In a large randomized trial of psychological intervention after myocardial infarction depression symptoms espanol purchase anafranil 75mg overnight delivery, no impact on recurrence or mortality was found (253) anxiety icd 9 cheap 25mg anafranil with visa. Another large trial that provided social support and treatment for depression also found no impact (254) lithium depression definition discount anafranil 50mg overnight delivery. Depression has a negative impact on quality of life (255, 256), and antidepressant therapy has been shown to signicantly improve quality of life and functioning in patients with recurrent depression who are hospitalized with acute coronary syndromes (257, 258). While these ndings provide some support for a causal interpretation of the associations, it is quite possible that they represent confounding or a form of reporting bias, as illustrated in a large Scottish cohort (263). In the meantime, physicians and health care providers should consider the whole patient. Early detection, treatment and referral of patients with depression and other emotional and behavioural problems are, in any case, important for reducing suffering and improving the quality of life, independent of any effect on cardiovascular disease. Multiple risk factor interventions Issue Are multiple risk factor interventions effective in reducing cardiovascular risk Evidence A Cochrane systematic review has evaluated the effectiveness of multiple risk factor interven tions for the primary prevention of cardiovascular disease in adults from general populations, occupational groups and high-risk groups (106). Eighteen randomized controlled trials involving counselling and/or health education, with or without pharmacological treatment, which aimed to affect more than one cardiovascular risk factor (smoking, diet, physical activity, blood pressure and blood cholesterol) were included. Overall, modest reductions in smoking prevalence, systolic blood pressure, diastolic blood pressure, and blood cholesterol were observed. The studies with the highest baseline levels of smoking prevalence, diastolic blood pressure or cholesterol levels demonstrated greater intervention-related reductions in these risk factors. The pooled effects of the ten trials with clinical event endpoints showed no signicant effect on total or cardiovascular disease mortality; this is consistent with the extent of changes in risk factors. However, trials that focused on participants with elevated blood pressure, and those that used drug treatment, demon strated signicant reductions in coronary heart disease mortality and total mortality. Interventions using personal or family counselling and education, with or without drug treatment, were more effective in modifying risk factors and reducing mortality in people at high risk because of raised blood pressure. These results argue in favour of multiple risk factor interventions for prevention of cardiovascular disease in multifactorial high-risk groups. For the general low-risk population, policy measures that create a conducive environment which facilitates behavioural change may have a greater impact at lower cost than individual counselling and therapeutic approaches. Blood pressure lowering Issue Does lowering blood pressure reduce cardiovascular risk Evidence Raised blood pressure is estimated to cause about 7 million premature deaths throughout the world, and 4. It is a major risk factor for cerebrovascular disease, coronary heart disease, and cardiac and renal failure. Raised blood pressure often coexists with other cardiovascular risk factors, such as tobacco use, overweight or obesity, dyslipidaemia and dysglycaemia, which increase the cardiovascular risk attributable to any level of blood pressure. Almost all clinical trials have conrmed the benets of antihypertensive treatment at blood pres sure levels of 160 mmHg (systolic) and 100 mmHg (diastolic) and above, regardless of the pres 40 Prevention of cardiovascular disease ence of other cardiovascular risk factors (264, 268). Observational data support lowering of these systolic and diastolic thresholds (269, 270). These trial results suggest that treatment for such high-risk patients should begin at the lower blood pressure thresholds. Although women are at lower total risk of cardiovascular disease for a given level of blood pressure, and randomized controlled trials generally include a greater proportion of men than women, the treat ment thresholds for systolic and diastolic pressure should be the same in men and women (274). Total risk of cardiovascular disease for any given level of blood pressure rises with age. For now, the treatment threshold should be unaffected by age, at least up to 80 years. Thereafter, decisions should be made on an individual basis; in any case, therapy should not be withdrawn from patients over 80 years of age (275, 276). In people over 55 years of age, the systolic blood pressure is more important (281), so the primary goal of therapy is to lower systolic blood pressure to 140 mmHg or less. In patients with high or very high cardiovascular risk, including diabetes or established vascular or renal disease, therefore, blood pressure should be reduced to 130/80 mmHg or less. These trials have demonstrated reductions in both cardiovascular mortality and morbidity with all three drug classes. For the endpoint of total cardiovascular mortality, these meta-analyses showed no strong evidence of differences between drug classes. At the beginning of the study, there was a fourth group treated with an alpha-blocker; this treatment was stopped prematurely because of an increased risk of combined cardiovascular disease, to which heart failure was a major contributor. The benets were largely attributable to protection against stroke, and were particularly striking in the diabetic group (290). The incidence of diabetes was also lower in the group on the amlodipine-based regimen. However, this difference could be largely explained by the difference in systolic blood pressure in the two groups (292). One such study included clinical trials in which a beta-blocker was used as the rst-line antihypertensive drug in at least half of all patients in one treatment group, with outcome data for cardiovascular morbidity and mortality, and all-cause mortality. This analysis found no difference in all-cause mortality or myocardial infarction, but the risk of stroke was lower with other antihypertensive drug regimens. However, when beta-blockers were compared with placebo or no treatment, they were found to signicantly reduce the risk of stroke. Beta-blockers are as efficacious as other classes of anti 42 Prevention of cardiovascular disease hypertensive drugs in reducing all-cause mortality and myocardial infarction, but appear to be less effective in reducing the risk of stroke (293). Another meta-analysis (295) investigated the efficacy of beta-blockers in different age groups. The efficacy was found to be similar to that of other antihypertensive agents in younger patients, but lower in older patients, with the excess risk being particularly marked for stroke. A recent Cocharane review assessed the effect of beta-blockers on mortality and morbidity endpoints, compared with placebo or no therapy for hypertension (296). Results showed a relatively weak effect of beta-blockers in reducing stroke and no effect on coronary heart disease. In choosing an antihypertensive drug therapy, there are a number of specic compelling indi cations (Table 7). For the majority of patients in resource-constrained settings, if there is no compelling indication for another class of drug, a low dose of a thiazide-like diuretic should be considered as the rst choice of therapy, on the basis of comparative trial data, availability and cost-effectiveness (286) (Table 7). As previously noted, for many patients, blood pressure should be reduced to lower levels than previously recommended, and more than one drug will often be required (75, 271, 272, 277, 284). It is important to increase gradually the dose of each drug to achieve optimum effect before adding another drug. Adherence to treatment is important to achieve the optimal reduc tion in blood pressure, and may be facilitated by a once-a-day dosage. If a second antihypertensive drug is added, it should be from a different drug class. In addition to the compelling indications listed in Table 7, other factors may favour the choice of certain drugs. Central alpha-agonists, such as cloni dine, or peripheral adrenergic blockers may be used as inexpensive therapies, despite the absence of outcome data. In certain conditions, specic drugs are contraindicated or should be used with caution (Table 7). While certain drugs may be more likely to induce side-effects in particular patients, they may still be used if they are strongly indicated and if the patients are carefully monitored. Beta-blockers, such as carvedilol and metoprolol, are increasingly used to treat stable heart failure. However, they may worsen heart failure and should not be given to individuals with decompensated heart failure (302). Evidence Many studies have shown that the benets of cholesterol-lowering therapy depend on the initial level of cardiovascular risk: the higher the total risk, the greater the benet. This is because the relative reductions in risk as a consequence of lipid lowering are approximately the same at differ ent levels of cardiovascular risk. The effectiveness of statins in patients with established atherosclerotic disease (principally coronary artery disease) is well established. Primary prevention trials, on the other hand, are more limited; however, the benets seen in these trials, as demonstrated by meta-analyses, are consistent with the overall results for all statin trials. Those in the treatment group had 31% fewer primary cardiovascular events than those given placebo (P<0. There were also signicant reductions in non-fatal myocardial infarction and death from all cardiovascular causes. In addition, the risks of myocardial infarction, unstable angina, coronary events, and cardiovascular events, and the need for coronary revascularization procedures, were signi cantly reduced in the treatment group. This was a mixed primary and secondary prevention trial, with 14% of patients having had prior coronary disease and 35% being diabetic. The failure to show a reduction in coronary heart disease events was attributed to this increased use of statins and other hypolipidaemic therapy in the patients given usual care. Thus, the difference in cholesterol levels in the two groups of patients was not as large as expected. Simvastatin reduced the rates of myocardial infarction, stroke and revascularization by about one-quarter. About one-third of the participants in this study were free of coronary heart disease. In this group, statin therapy reduced major vascular events by 22% compared with placebo (P = 0. All patients had at least one of the following: retinopathy, albuminuria, current smoking, or hypertension. Patients (n = 2102) were randomly assigned to receive uvastatin or placebo, and followed up for 5. This was a mixed primary and secondary prevention study, designed to test the benets of statin treat ment in the elderly. Participants either had existing vascular disease (coronary, cerebral or periph eral) or were at risk of such disease (because of smoking, hypertension or diabetes). The primary endpoint was a composite of coronary death, non-fatal myocardial infarction, and fatal and non fatal stroke. Four studies met these criteria: the Lipid Research Clinic Primary Prevention Trial, the Helsinki Heart Study, the West of Scotland Coronary Prevention Study, and the Air Force/Texas Coronary Prevention Study (318, 319, 327, 328). Lipid-lowering drug treatment reduced the odds of a coronary heart disease event by 30% (summary odds ratio 0. When the analysis was limited to trials that used statins a slightly stronger effect on all outcomes was found, but there was still no signicant reduction in all-cause mortality (although none of these studies was individually powered for this endpoint). Another review of lipid-lowering treatment with statins found that coronary heart disease events and all-cause mortality were reduced in primary prevention populations (329). This review, unlike the meta-analysis mentioned above (326), did not include the large Air Force/Texas trial, which was conducted later. It included the Kuopio atherosclerosis prevention study, a trial in which about 10% of subjects had a history of myocardial infarction (330), and which was not included in the more recent meta-analysis. Data from 15 trials with 63 410 participants and a mean duration of treatment of 3. Overall, statin treatment reduced the relative risk of coronary events, cardiovascular disease mortality, non-fatal strokes and all-cause mortality. There was a 23% reduction in myocardial infarction and coronary death, a 24% reduction in the need for coronary revasculariza tion, and a 17% reduction in fatal and non-fatal strokes, giving a 21% reduction overall in major cardiovascular events. In some trials, participants had high blood pressure, diabetes or ischaemic heart disease. Statins reduced ischaemic heart disease events at age 60 by an estimated 61% in the long term; there was little reduction in the rst year but a 51% reduction by the third year. They also reduced the overall risk of stroke by 17%, preventing thromboembolic stroke but not haemorrhagic stroke.

People who are immunocompromised anxiety from alcohol cheap 25 mg anafranil mastercard, are older than 40 years of age depression symptoms restlessness 25mg anafranil sale, or have liver disease should receive Immune Globulin (see Hepatitis A severe depression clinical generic 75mg anafranil otc, p 361) depression understanding buy genuine anafranil on line. Update: Prevention of hepatitis A after exposure to hepatitis A virus and in international travelers anxiety feeling safe 75 mg anafranil. Respiratory tract viruses mood disorder 1 buy anafranil american express, however, are associated with exacerba tions of reactive airway disease and an increase in the incidence of otitis media and can cause signifcant complications for children with chronic respiratory tract disease, such as cystic fbrosis, or for children who are immunocompromised. Infuenza virus infection is a common cause of febrile respiratory tract disease and school absenteeism. Annual infuenza immunization should be administered to children and adults 6 months of age and older (see Infuenza Vaccine, p 445). Mycoplasma pneumoniae causes upper and lower respiratory tract infection in school aged children, and outbreaks of M pneumoniae infection occur in communities and schools. The nonspecifc symptoms and signs associated with this organism make distinguishing M pneumoniae infection from other causes of respiratory tract illness diffcult. Antimicrobial therapy does not necessarily eradicate the organism or prevent spread. Thus, intervention to prevent secondary infection in the school setting is diffcult. Mycoplasma outbreaks in schools should be reported to the local health department. Symptomatic contacts of students with pharyngitis attributable to group A streptococ cal infection should be evaluated and treated if streptococcal infection is demonstrated. Infected students may return to school 24 hours after initiation of antimicrobial therapy. Students awaiting results of culture or antigen-detection tests who are not receiving anti microbial therapy may attend school during the culture incubation period unless there is an associated fever or the infection involves a child with poor hygiene and poor control of secretions. Infected people are not considered contagious after 24 hours of appropriate antimicrobial therapy. After discharge from the hospital, they pose no risk to classmates and may return to school. Prophylactic antimicrobial therapy is not recommended for school contacts in most circumstances. Close observation of contacts is recommended, and they should be evaluated promptly if a febrile illness develops. Students who have been exposed to oral secretions of an infected student, such as through kissing or sharing of food and drink, should receive chemoprophylaxis (see Meningococcal Infections, p 500). Students and staff members with documented pertussis should be excluded until they have received at least 5 days of the recommended course of azithromycin, clarithromy cin, or erythromycin therapy and are able to participate in school-related activities. Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine should be substituted for a single dose of tetanus and diphtheria toxoids (Td) vaccine for children 7 years of age or older and adults in the primary catch-up series or as a booster dose if age appropriate (see Fig 1. Before adolescence, children with tuberculosis generally are not contagious, but students who are in close contact with a child, teacher, or other adult with tuberculosis should be evaluated for infection, including tuberculin skin testing or interferon-gamma release assay (see Tuberculosis, p 736). An adolescent or adult with tuberculosis almost always is the source of infection for young children. If an adult source outside the school is identifed (eg, parent or grandparent of a student), efforts should be made to determine whether other students have been exposed to the same source and whether they warrant evaluation for infection. Children with erythema infectiosum should be allowed to attend school, because the period of contagion occurs before a rash is evident. Parvovirus B19 infection poses no risk of signifcant illness for healthy classmates, although aplastic crisis can develop in infected children and adults with sickle cell disease or other hemoglobinopathies. The relatively low risk of fetal damage should be explained to pregnant students and teachers exposed to children in the early stages of parvovirus B19 infection, 5 to 10 days before appearance of the rash. Exposed pregnant women should be referred to their physician for counseling and possible serologic testing. Infections Spread by Direct Contact Infection and infestation of skin, eyes, and hair can spread through direct contact with the infected area or through contact with contaminated hands or fomites, such as hair brushes, hats, and clothing. Lesions may develop when these organisms are passed from a person with infected skin to another person. Organisms also can be transmitted to open skin lesions in the same child or to other children. Although most skin infections attributable to S aureus and group A streptococcal organisms are minor and require only topical or oral antimicrobial therapy, person-to-person spread should be interrupted by appropriate treatment whenever lesions are recognized. Exclusion of any infected child with an open or draining lesion that cannot be covered is recommended. Infection is spread through direct contact with herpetic lesions or asymp tomatic shedding of virus from oral or genital secretions. Infection occurs through direct contact or through contamination of hands followed by autoinoculation. Topical anti microbial therapy is indicated for bacterial conjunctivitis, which usually is distinguished by a purulent exudate. Conjunctivitis attributable to adenoviruses or enteroviruses is self-limited and requires no specifc antiviral therapy. Spread of infection is minimized by careful hand hygiene, and infected people should be presumed contagious until symptoms have resolved. Except when viral or bacterial conjunctivitis is accompanied by systemic signs of illness, infected children should be allowed to remain in school once any indicated therapy is imple mented, unless their behavior is such that close contact with other students cannot be avoided. Fungal infections of the skin and hair are spread by direct person-to-person contact and through contact with contaminated surfaces or objects. Trichophyton tonsurans, the pre dominant cause of tinea capitis, remains viable for long periods on combs, hair brushes, furniture, and fabric. The fungi that cause tinea corporis (ringworm) are transmissible by direct contact. The fungi that cause these infections have a predilection for moist areas and are spread through direct contact and contact with contaminated surfaces. Students with fungal infections of the skin or scalp should be encouraged to receive treatment both for their beneft and to prevent spread of infection. However, lack of treatment does not necessitate exclusion from school unless the nature of their con tact with other students could potentiate spread. Students with tinea pedis should be excluded from swim ming pools and from walking barefoot on locker room and shower foors until treatment has been initiated. Spread of infection by students with tinea capitis may be decreased by use of selenium sulfde shampoos, but treatment requires systemic antifungal therapy (see Tinea Capitis, p 712). Sarcoptes scabiei (scabies) and Pediculus capitis (head lice) are transmitted primarily through person-to-person contact. The scabies parasite survives on clothing for only 3 to 4 days without skin contact. Combs, hair brushes, hats, and hair ornaments can transmit head lice, but away from the scalp, lice do not remain viable. Caregivers who have prolonged skin-to skin contact with students infested with scabies may beneft from prophylactic treatment (see Scabies, p 641). Manual removal of nits after treatment with a pediculicide is not necessary to prevent reinfestation (see Pediculosis Capitis, p 543). Infections Spread by the Fecal-Oral Route For developmentally typical school-aged children, pathogens spread via the fecal oral route constitute a risk only if the infected person fails to maintain good hygiene, including hand hygiene after toilet use, or if contaminated food is shared between or among schoolmates. If an outbreak occurs, consultation with local public health authorities is indicated before initiating interventions. Enteroviral infections probably are spread via the oral-oral route as well as by the fecal-oral route. The incidence is so high when outbreaks occur during summer and fall epidemics that control measures specifcally aimed at the school classroom likely would be futile. Person-to-person spread of bacterial, viral, and parasitic enteropathogens within school settings occurs infrequently, but foodborne outbreaks attributable to enteric patho gens can occur. Symptomatic people with gastroenteritis attributable to an enteric patho gen should be excluded until symptoms resolve. Children in diapers at any age and in any setting constitute a far greater risk of spread of gastrointestinal tract infection attributable to enteric pathogens. Guidelines for control of these infections in child care settings should be applied for school-aged students with developmental disabilities who are diapered (see Children in Out-of-Home Child Care, p 133). Infections Spread by Blood and Body Fluids Contact with blood and other body fuids of another person requires more intimate exposure than usually occurs in the school setting. However, care required for children with developmental disabilities may result in exposure of caregivers to urine, saliva, and in some cases, blood. The application of Standard Precautions for prevention of trans mission of bloodborne pathogens, as recommended for children in out-of-home child care, prevents spread of infection from these exposures (see Children in Out-of-Home Child Care, p 133). School staff members who routinely provide acute care for children with epistaxis or bleeding from injury should wear disposable gloves and use appropriate hand hygiene measures immediately after glove removal for protection from bloodborne pathogens. Parents and students should be educated about the types of exposure that present a risk for school contacts. The infec tion status of patients should not be disclosed to other participants or the staff of athletic programs. This may be protective for other participants and for infected athletes themselves, decreas ing their possible exposure to bloodborne pathogens other than the one(s) with which they are infected. Wrestling and boxing probably have the greatest potential for con tamination of injured skin by blood. Human immunodef ciency virus and other blood-borne viral pathogens in the athletic setting. Even if these precautions are adopted, the risk that a participant or staff member may become infected with a bloodborne pathogen in the athletic setting will not be eliminated entirely. Hands should be cleaned with soap and water or an alcohol-based antiseptic agent as soon as possible after gloves are removed. Wounds must be covered with an occlusive dressing that will remain intact and not become soaked through during further play before athletes return to competition. The decontaminated equipment or area should 1 be in contact with the bleach solution for at least 30 seconds. If the caregiver does not have appropriate protective equipment, a towel may be used to cover the wound until an off-the-feld location is reached where gloves can be used during more defnitive treatment. Infection Control and Prevention for Hospitalized Children Health care-associated infections are a major cause of morbidity and mortality in hos pitalized children, particularly children in intensive care units. Hand hygiene before and after each patient contact remains the single most important practice in prevention and control of health care-associated infections. Guidelines for prevention of intravascular catheter-related infections are available. The Cystic Fibrosis Foundation published an evidence-based guideline for prevention of transmission of infectious agents among cystic fbrosis patients in 2003. Physicians and infection control professionals should be familiar with this increasingly complex array of guidelines, regulations, and standards. Ongoing infection prevention and control programs should educate, imple ment, reinforce, document, and evaluate recommendations on a regular basis. The Healthcare Infection Control Practices Advisory Committee in 2007 updated evidence-based isolation guidelines for preventing transmission of infectious agents in health care settings. Adherence to these 1 isolation policies, supplemented by health care facility policies and procedures for other aspects of infection and environmental control and occupational health, should result in reduced transmission and safe patient care. Adaptations should be made according to the conditions and population served by each facility. Routine and optimal performance of Standard Precautions is appropriate for care of all patients regardless of diagnosis or suspected or confrmed infection status. In addition to Standard Precautions, pathogen and syndrome-based Transmission Based Precautions are used when caring for patients who are infected or colonized with pathogens transmitted by airborne, droplet, or contact routes. Barrier techniques are recommended to decrease exposure of health care personnel to body fuids. Precautions are used with all patients when exposure to blood and body fuids is anticipated, because medical history and examination cannot reliably identify all patients infected with human immunodef ciency virus or other bloodborne infectious agents. Standard Precautions decrease trans mission of microorganisms from patients who are not recognized as harboring potential pathogens, such as antimicrobial-resistant bacteria. Hand hygiene should be performed either with alcohol-based agents or soap and water before wearing and immediately after removing gloves, between patient contacts, and when otherwise indicated to avoid transfer of microorganisms to other patients and to items in the environment. When hands are visibly dirty or contami nated with proteinaceous material, such as blood or other body fuids, hands should be washed with soap and water for at least 20 seconds. When exposure to spores (eg, Clostridium diffcile) or norovirus is likely, handwashing with soap and water is preferred. Gloves should be changed between tasks and procedures on the same patient after contact with material that may contain a high concentration of microorganisms (eg, purulent drainage). Masks should be worn when placing a catheter or injecting material into the spinal canal or subdural space (eg, during myelograms and spinal or epidural anesthesia). Soiled gowns should be removed promptly and carefully to avoid contamination of clothing.

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May lead to focal infection in any organ or tissue of the body) Incubation 6 hours to 3 days Fact Fatality rate of 5-10% Treatment Antibiotic combination: chloramphenicol anxiety drugs buy anafranil 25mg with visa, neomycin depression test learnmyself purchase 25 mg anafranil mastercard, ampicillin Shigellosis* Bacteria Genus Species All Shigella species Host Range Captive non-human primates Transmission Oral-fecal route Symptoms Ranges from asymptomatic carrier to severe bacillary dysentery with high fevers bipolar depression medication and weight loss anafranil 75 mg for sale, weakness anxiety otc medication cheap anafranil 50 mg line, severe abdominal cramps depression laziness purchase cheap anafranil on-line, prostration depression bible cheap anafranil master card, edema of the face and neck, and diarrhea with blood, mucous and inflammatory cells Incubation Varies by species. Droplet transmission via aerosols of urine Symptoms Phase 1: headache, muscle ache, eye pain with bright lights, chills and fever. Skin lesions, swollen lymph glands, abscesses septicemia or pneumonia Incubation 2-4 days Fact Relatively uncommon disease for humans, but when lef untreated, has 95% fatality rate Treatment Chloramphenicol, doxycycline, sulfisoxazole, or cotrimoxazole. Transmission Probably arthropod-borne via the bite of an infected sandfly, mosquito or blackfly; by direct contact with infected animals (vesicular fluid, saliva) Symptoms Infuenza-like illness, malaise, fever, headache, nausea and vomiting Incubation 24-48 hours Fact Documented hazard to personnel (45 laboratory-acquired infections before 1980) handling infected livestock, tissues and virulent isolates Treatment Virus is self-limiting and illness is short in duration. Cyst is resistant to drying Symptoms Frequent passage of feces/stool, loose stools and vomiting. Can be frequent urge with high or low volume of stool, with or without some associated mucus and even blood Incubation 2 days to several months to even years Fact Harmless amoebas can live in the intestines for years without causing symptoms. Attacks can last from a few days to weeks Treatment Antiamebic drugs (Iodoquinol, metronidazole) and antibiotics to treat associated bacterial infections Giardiasis Giardiasis Genus Species Giardia lamblia Host Range Dogs, monkeys Transmission Drinking contaminated water, person-to-person contact, eating contaminated food, and direct contact with infected animals Symptoms Ranges from asymptomatic to nausea, fatigue, anorexia, severe diarrhea and high fever Incubation 3-25 days Fact Most common waterborne diarrheal disease in humans Treatment Quinacrine hydrochloride, metronidazole, tinidazole, albendazole and furazolidone Balantadidiasis Parasite (protozoa) Genus Species Balantidium coli Host Range Monkeys, pigs, and other nonhuman primates readily transmitted to humans Transmission Direct contact with feces, person-to-person transmission Symptoms Ranges from asymptomatic to severe diarrhea Incubation 4-5 days Fact Cysts survive for long periods in the environment Treatment Tetracycline, Iodoquinol, metronidazole Appendix D 157 Malaria Parasite (protozoa) Genus Species Plasmodium species: P. Results are promising Treatment Chloroquine, primaquine phosphate, Malorone Toxoplasmosis Parasite (protozoa) Genus Species Toxoplasma gondii Host Range Amazing lack of host specificity. Severe infection can cause severe tissue damage, systemic damage of various tissues in the body and potential death Incubation skin 7 hours; lung 1 week; intestines 2 wks; average 4-21 days Fact the parasite penetrates the skin and migrates to the lungs. Then it travels up to the mouth and is swallowed into the intestinal tract Treatment Ivermectin with Albendazole as the alternative Trichinosis Nematode Genus Species Trichinella spiralis Host Range Generally pigs or cattle Transmission Eating undercooked flesh of animals infected with the larvae Symptoms Nausea, vomiting, diarrhea, fever, neurological disorders, possible cardiac involvement Incubation Abdominal symptoms: 1 2 days. Biosafety defines the containment conditions under which infectious agents can be safely manipulated. Biohazardous Agents A bacterium, virus, or other microorganism that can cause disease in healthy individuals, animals or plants. Use the drop down menu and select Biosafety & Biosecurity Biosafety & Biosecurity Sta Ellyn Segal, Ph. Ph: (650) 724-0798 Biosafety & Biosecurity Specialist Fax: (650) 725-3468 simones2@stanford. Ph: (650) 724-0986 Biosafety & Biosecurity Specialist Fax: (650) 725-3468 umamoto@stanford. Fax: (650) 725-3468 Biosafety & Biosecurity Specialist Contact Information shirly@stanford. Shedd Aquarium) Seahorses, pipefishes and seadragons are marine fishes found globally which belong to the family Syngnathidae. These fishes are very popular within the public aquarium and the hobbyist communities. Historically seahorses were considered very difficult to maintain in a captive environment, but continued efforts by hobbyist and professional aquarium staff have resulted in the development of techniques that now enable aquarists to maintain and reproduce seahorse species successfully. However, there are still difficulties with seahorse husbandry, and although the life cycle for some species has been closed, we are still a long way from understanding all of the husbandry requirements and health management practices for many seahorse species. More and more public aquariums are utilizing financial and physical resources by displaying these unique animals. Several special seahorse exhibits have been successfully run in public aquariums since 2000, including at the John G. Smaller displays of seahorses and their relatives are commonplace in aquariums internationally. There are now over 1,100 zoos and aquariums worldwide with over 800 million visitors annually. In North America alone, there are over 185 zoos, aquaria, oceanariums, and wildlife parks with an annual attendance over 130 million. These organizations support membership excellence in conservation, education, science, and recreation. They also manage breeding programs for endangered species and species that benefit from co-ordinated programmes to advance husbandry and management. Combined efforts to improve the husbandry, management and conservation of seahorses was initiated at a Project Seahorse workshop at the John G. Participants came from diverse professional backgrounds including directors, nutritionists, veterinarians, researchers, and husbandry staff. In 2005, the list grew to 284 members and has developed as an effective communication tool. The majority 3 of the discussions relate to disease treatments, exchanges of captive bred animals, other husbandry issues and information dissemination on seahorse-related issues. These were established to obtain data, analyze techniques, and develop and disseminate policies and information on these fishes. These groups also promote the conservation of seahorses and seadragons through the support of a regional collection plan, ex-situ and in-situ research, public display and public education programs. The two species of seadragons are also included: Phyllopteryx taeniolatus and Phycodurus eques. Population management of seahorses in zoos, aquariums and independent organizations are critical to the goals of North American and European conservation strategies. Well-managed populations, research, record keeping, and education are the stated priorities of these strategies. To provide purebred species lines to zoo and aquaria partners for conservation research and education purposes 2. To maintain minimum genetic diversity within each captive population, improving the health and fitness of the captive strains. Many aquariums are finding that special exhibits are a powerful tool to raise awareness of seahorse conservation issues and engage the public. By working together as a community and by channeling resources into appropriate actions, it is hoped that zoos and aquariums can continue to play an important role in assisting with seahorse conservation. Proceedings of the First International Aquarium Workshop on Seahorse Husbandry, Management, and Conservation. A total of 54 institutions responded in 2005, compared to 40 institutions in 2000 (table 1). The complete data are recorded in Appendix 2 (seahorses), 3 (seadragons) and 4 (other syngnathids). Where taxonomic uncertainty remained, seahorses were not included in the survey results. Aquarium geographic region Number of Number of responding responding aqms aqms 2000 2005 Australia/New Zealand 1 3 Europe 11 22 North America 26 28 South America 2 1 Total 40 54 Table 1: Number of aquariums from different regions responding to seahorse survey in 2000 and 2005. Eighteen species of seahorse were encountered in public aquariums in 2000 and 16 (plus one hybrid) in 2005 (figure 1). Overall, there has been very little change in the species number and diversity between the two surveys. There were some issues with species identification in 2000 that may have under-reported H. Regionally, there were major differences in the seahorses species held (figure 2), although this was skewed by the low number of responses from Australia/New Zealand and Central America (table 1). America 8 6 4 2 0 Seahorse species Figure 2: Number of institutions holding each seahorse species in each of the geographic regions surveyed. Of the 17 species reported in the 2005 survey of seahorses in public aquariums, 16 were reported to show breeding activity 3). However, only 11 of these are also being reared defined as offspring reaching reproductive age. While it is recognized that some institutions may actively choose not to breed or rear their seahorses, it is important that these are active management decisions. If breeding and rearing is not possible, then further research should be carried out to improve the husbandry success with these species. This demonstrates that the importance of the first priority of the programme for these two species to successfully and repeatedly close the life cycle. The viability of this programme is under review due to the problems with the small founder population. This suggests that further work is required to improve the husbandry and survival of these species. These results strongly suggest that the goals of the programmes and the number of species, optimal population size for holding and breeding plans for these species need to be reviewed. They also emphasise the continued importance of husbandry research in public aquariums for seahorses and their relatives. Revision of the Australian seahorses of the genus Hippocampus (Syngnathiformes: Syngnathidae) with descriptions of nine new species. Seahorses in trade Seahorses are threatened by direct exploitation, accidental capture in non-selective fishing gear (bycatch), and degradation of their coastal habitats. Most exploited seahorses find their way into large scale, unmanaged and unmonitored international trade. Extensive trade surveys carried out by Project Seahorse have revealed concerning trends. In 1996, it was estimated that at least 32 nations were involved in an annual trade involving more than 16 million and probably close to 20 million animals (Vincent 1996). Seahorses are sold dried for traditional medicines, tonic foods and curiosities, and live for ornamental display. Sadly, research suggests that live trade for public and private aquaria, while only representing a relatively small proportion of total trade, can be the largest pressure on certain wild populations. Conservation Concerns the impacts of global trade on seahorse populations are considerable, especially when combined with damage to their vulnerable inshore marine habitats. A combination of customs records, quantitative research and qualitative information indicates that in certain places seahorse catches and/or trades have declined markedly. This reflects a loss of population rather than a drawdown of the trade: estimated population declines of between 15 and 50 percent over five-year periods 2 are common. Many countries additionally have established their own domestic conservation assessments or have drawn up regulations that recognize the threat to seahorse populations (see Lourie et al. With millions of seahorses being traded on an annual basis, it appeared likely that international trade was contributing to the observed population declines. Non-detriment findings must be filed prior to being granted an export permit as they certify that the exports will not threaten the survival of the species in the wild. Non-Detriment Findings Despite the formal requirement for a non-detriment finding, i. This is often due to the lack of programmes to monitor both the levels of harvest and the status of wild populations of species exploited for trade. Seahorses have become a test case to see how fisheries management tools could be used to meet the sustainable trade requirements of the Convention. A single minimum permissible height for all seahorse species in international trade appears to be both biologically appropriate and socially acceptable (Martin-Smith et al. Currently, the number of juvenile seahorses in trade bodes poorly for population recovery from overexploitation. Size-selective regulations are frequently developed to enhance sustainable use of marine species as varied as cod and crustaceans. Limits (maxima or minima) and dimensions are set with reference to the biology, life-history strategy and catch methods for the target species. Ideally, a minimum size limit should be set so as to allow animals to reproduce before being caught. The Animals Committee further concluded that a height of 10 cm would currently serve as the most appropriate minimum size for the genus Hippocampus. Some aquarists have asked how the possible adoption of the minimum size limit by a Party this will affect them. It is a committee of experts that provides technical support to decision-making about species. The intention of a minimum size limit is to permit the fish to reproduce and replace itself in the population before being caught and traded. The concept that a fish must be allowed to grow large enough to reproduce is one that can be easily understood permitting community buy in. From the perspective of compliance and enforcement, regulators, local wardens and others involved in enforcement can measure specimens that have been retained or that are proposed for trade. A 10 cm minimum size limit would permit both reproduction and continued trade in most species that are currently exported. It serves as an initial approach to making non-detriment findings while Parties assess international trade levels, impacts on domestic species, and potential alternative management tools which could supplement or replace the minimum size limit. A minimum size limit of 10 cm should be sufficient to permit reproduction in most species as it is slightly above the currently inferred maximum size at onset of sexual maturity for most species, so should allow reproduction to occur (see Figure at end of section). Initial research suggests that of the 10 small species of seahorses that generally do not reach the minimum size limit, only four of the ten species under 10 cm are currently in trade, mostly for aquarium display. For example, in addition to the minimum size limit, recommended complementary auxiliary and voluntary measures included a quota on the export levels at or below current levels, and a cap on the issuance of new licenses. For example, some countries have regulations that make targeted removal of seahorses from the wild an illegal activity, so any broodstock obtained in this way would be illegal. Other countries ban trawling in coastal zones, and so any seahorses obtained incidentally by trawl fisheries in these zones would also be considered illegal. It is essential to review any national legislation that may relate to the acquisition of wild seahorses before you attempt to move them across international borders. Transportation Guidelines 9 the Convention states that an export permit must not be issued until the Management Authority of the State of export is satisfied that any living specimen will be so prepared and shipped as to minimize the risk of injury, damage to health or cruel treatment. This publication is an essential source on how to ship animals safely, sensitively and cost-effectively. It specifies the minimum requirements for the international transport of animals and wildlife, and indicates what precautions airlines, shippers, cargo agents and animal care professionals should take on the ground and in the air. You should ensure that the transport of any live seahorses conforms to these guidelines.

Facilities should develop policies that govern the identifcation depression symptoms boyfriend 25 mg anafranil with mastercard, marking and handling of sensitive information definition of depression in economics buy anafranil with american express. Transport security measures should be instituted to ensure that appropriate authorizations have been received and that adequate communication between facilities has occurred before anxiety worksheets discount anafranil 75 mg amex, during depression symptoms quotes best purchase anafranil, and after transport of pathogens or other potentially hazardous biological materials mood disorder 4 year old buy cheap anafranil 75mg online. This communication chain should include laboratory and program offcials depression symptoms journal buy anafranil with paypal, institution management, and any relevant regulatory or public authorities. The roles and responsibilities of all involved offcials and programs should be clearly defned. Security Updates and Re-evaluations the biosecurity risk assessment and program should be reviewed and updated routinely and following any biosecurity-related incident. Select Agents If an entity possesses, uses or transfers select agents, it must comply with all requirements of the National Select Agent Program. This is accomplished by limiting opportunities for exposure, promptly detecting and treating exposures, and using information gained from work injuries to further enhance safety precautions. Occupational health and safety in biomedical research settings is a responsibility shared by healthcare providers, safety specialists, principal investigators, employers, and workplace personnel. Workers should be fully informed of the available medical support services and encouraged to utilize them. Requisite occupational medical services are described below and expanded discussions of the principles of effective medical support services are available in authoritative texts. Risk assessments should defne potential hazards and exposures by job responsibility. The interaction between worker, healthcare provider and employer may be complex, such as a contract worker who uses his own medical provider or uses contract medical services. That information should be reinforced 114 Biosafety in Microbiological and Biomedical Laboratories annually, at the time of any signifcant change in job responsibility, and following recognized and suspected exposures. Occupational Health Support Service Elements Preplacement Medical Evaluations Workers who may be exposed to human pathogens should receive a preplacement medical evaluation. When occupational exposure to human pathogens is a risk, employers should consider collecting and storing a serum specimen prior to the initiation of work with the agent. It can be used to establish baseline sero-reactivity, should additional blood samples be collected for serological testing subsequent to a recognized or suspected exposure. Some occupational exposures present substantially more hazard to identifable sub-populations of workers. Serologic testing should be used to document baseline vulnerability to specifc infections to which the worker might Occupational Health and Immunoprophylaxis 115 be exposed, and non-immune workers should be adequately informed about risks. In specifc settings, serologic documentation that individual workers have pre-existing immunity to specifc infections also may be required for the protection of research animals. If the potential consequences of infection are substantial and the protective beneft from immunization is proven, acceptance of such immunization may be a condition for employment. Use of investigational products, or of licensed products for off-label indications must be accompanied by adequate informed consent outlining the limited availability of information on safety and effcacy. Periodic Medical Evaluations Routine, periodic medical evaluations generally are not recommended; however, limited periodic medical evaluations or medical clearances targeted to job requirements may occasionally be warranted. Before asymptomatic workers without specifc exposures are tested for seroreactivity, the beneft of such testing should be justifed, plans for further investigation of indeterminate test results should be delineated, and clearly defned criteria for interpretation of results should be developed. Medical Support for Occupational Illnesses and Injuries Workers should be encouraged to seek medical evaluation for symptoms that they suspect may be related to infectious agents in their work area, without fear of reprisal. A high index of suspicion for potential occupational exposures should be maintained during any unexplained illness among workers or visitors to worksites containing biohazards. Modes of transmission, as well as the clinical presentation of infections acquired through occupational exposures, may differ markedly from naturally acquired infections. A close working relationship with the research or clinical program in which the affected employee works is absolutely essential. Occupational Health and Immunoprophylaxis 117 the adequacy and timeliness of wound cleansing or other response after an exposure occurs may be the most critical determinant in preventing infection. Accurate quantifcation of risk associated with all exposures is not possible, and the decision to administer post-exposure prophylaxis may have to be made quickly and in the absence of confrmatory laboratory testing. The clinician may need to make a best-estimate based 118 Biosafety in Microbiological and Biomedical Laboratories upon knowledge of similar agents, exposure circumstances, and advice received from knowledgeable experts. Appropriate post-exposure prophylactic response is always pathogen and exposure dependent, and may be host-factor dependent and infuenced by immediate post-exposure management. Before prophylactic treatment is undertaken, confrm the likelihood that an exposure occurred, that prophylaxis is indicated and is not contraindicated by past medical history. The supervisor must receive a description of the accident or incident, confrm the circumstances of the injury or exposure and provide relevant advice. The report also should be distributed to all other relevant parties, such as the safety professional. When immediate institution of post-exposure prophylaxis may delay seroconversion, or when the agent to which the worker was exposed results in seroconversion completed over months. If sero-reactivity is evident in the earliest specimen, it is important to re-test that specimen in tandem with serum specimens archived prior to occupational exposure and/or collected serially over time to investigate whether a change in titer suggestive of new infection can be identifed. Occupational Health and Immunoprophylaxis 119 In some exposure situations, it may be appropriate to store serially collected serum samples, and to send them for testing as evidence of seroconversion only if symptoms develop that suggest an infection may have occurred. Caution should be taken to avoid placing more confdence in testing outcomes than can be justifed by the nature of the assays. Most mammals are susceptible to anthrax; it mostly affects herbivores that ingest spores from contaminated soil and, to a lesser extent, carnivores that scavenge on the carcasses of diseased animals. While naturally occurring disease is no longer a Agent Summary Statements: Bacterial Agents 123 signifcant public health problem in the United States, anthrax has become a bioterrorism concern. A Department of Commerce (DoC) permit may be required for the export of this agent to another country. The organism is a fastidious, small gram-negative coccobacillus that requires highly specialized culture and transport media for cultivation in the laboratory. Occupational Infections Occupational transmission of pertussis has been reported, primarily among healthcare workers. Although the number of reported pertussis cases declined by over 99% following the introduction of vaccination programs in the 1940s, the 3 to 4-year cycles of cases have continued into the post-vaccination era. Brucella species the genus Brucella consists of slow-growing, very small gram-negative coccobacilli whose natural hosts are mammals. Accidental self-inoculation with vaccine strains is an occupational hazard for veterinarians. Natural Modes of Infection Brucellosis (Undulant fever, Malta fever, Mediterranean fever) is a zoonotic disease of worldwide occurrence. Multiple routes of transmission have been identifed, including direct contact with infected animal tissues or products, ingestion of contaminated milk, and airborne exposure in pens and stables. Cases have occurred in clinical laboratory settings from sniffng bacteriological cultures29 or working on open bench tops. The infectious dose of Brucella is 10-100 organisms by aerosol route and subcutaneous route in laboratory animals. While endemic foci of infection exist in some areas of the world, glanders due to natural infection is extremely rare in he United States. Agent Summary Statements: Bacterial Agents 127 Occupational Infections Glanders occurs almost exclusively among individuals who work with equine species and/or handle B. Clinical glanders no longer occurs in the Western Hemisphere or in most other areas of the world, although enzootic foci are thought to exist in Asia and the eastern Mediterranean. Workers should take precautions to avoid exposure to aerosols from bacterial cultures, and to tissues and purulent drainage from victims of this disease. This organism is the causative agent of melioidosis, an unusual bacterial disease characterized by abscesses in tissues and organs. There are two reports of melioidosis in laboratory workers who were infected by aerosols or via skin exposure. While the infective dose is not frmly established, ingestion of as few as 500-800 organisms has caused symptomatic infection. Chlamydiae are nonmotile, gram-negative bacterial pathogens with obligate intracellular life cycles. The major sources of laboratory associated psittacosis are contact with and exposure to infectious aerosols in the handling, care, or necropsy of naturally or experimentally infected birds. Early reports commonly attributed infections to exposure to aerosols formed during nasal inoculation of mice or inoculation of egg yolk sacs and harvest of chlamydial elementary bodies. Infections are associated with fever, chills, malaise, and headache; a dry cough is also associated with C. The route of infection was attributed to inhalation of droplet aerosols created during procedures associated with culture and harvest of the agent from cell culture. With all species of Chlamydia, mucosal tissues in the eyes, nose, and respiratory tract are most often affected by occupational exposures that can lead to infection. Exposure to infectious aerosols and droplets, created during the handling of infected birds and tissues, are the primary hazards to laboratory personnel working with C. Wetting the feathers of infected birds with a detergent disinfectant prior to necropsy can appreciably reduce the risk of aerosols of infected feces and nasal secretions on the feathers and external surfaces of the bird. Gloves are recommended for the necropsy of birds and mice, the opening of inoculated eggs, and when there is the likelihood of direct skin contact with infected tissues, bubo fuids, and other clinical materials. Purifed botulinum neurotoxin is a 150 kDa protein that acts selectively on peripheral cholinergic nerve endings to block neurotransmitter release. The toxin also acts on autonomic nerve endings where blockade of transmission can produce a variety of adverse effects. Occupational Infections There has been only one report of botulism associated with handling of the toxin in a laboratory setting. Use of appropriate personal protective equipment should prevent potential exposure through mucus membranes. Although spore-forming, there is no known risk to spore exposure except for the potential for the presence of residual toxin associated with pure spore preparations. Laboratory safety protocols should be developed with the focus on prevention of accidental exposure to the toxin produced by these Clostridia species. Vaccination is recommended for all personnel working in direct contact with cultures of neurotoxin producing Clostridia species or stock solutions of Botulinum neurotoxin. Clostridium tetani and Tetanus toxin Clostridium tetani is an anaerobic endospore-forming gram-positive rod found in the soil and an intestinal tract commensal. It produces a potent neurotoxin, tetanospasmin, which causes tetanus, an acute neurologic condition characterized by painful muscular contractions. Elevated incidence rates also were observed for persons aged over 60 years, diabetics, and intravenous drug users. Special Issues Vaccines the vaccination status of workers should be considered in a risk assessment for workers with this organism and/or toxin. The organism is easily grown in the laboratory on media containing 5% sheep blood. Travel to endemic areas or close contact with persons who have returned recently from such areas, increases risk. Naturally occurring diphtheria is characterized by the development of grayish white membranous lesions involving the tonsils, pharynx, larynx, or nasal mucosa. Francisella tularensis Francisella tularensis is a small gram-negative coccobacillus that is carried in numerous animal species, especially rabbits, and is the causal agent of tularemia (Rabbit fever, Deer fy fever, Ohara disease, or Francis disease) in humans. The incubation period varies with the virulence of the strain, dose and route of introduction but ranges from 1-4 days with most cases exhibiting symptoms in 3-5 days. Natural Modes of Infection Tick bites, handling or ingesting infectious animal tissues or fuids, ingestion of contaminated water or food and inhalation of infective aerosols are the primary transmission modes in nature. Infection has been more commonly associated with cultures than with clinical materials and infected animals. They are obligately aerobic, slow-growing, nonfermentative organisms that have a unique requirement for L-cysteine and iron salts for in vitro growth. The spectrum of illness caused by Legionella species ranges from a mild, self-limited fu-like illness (Pontiac fever) to a disseminated and often fatal disease characterized by pneumonia and respiratory failure (Legionnaires disease). Laboratory Safety and Containment Recommendations the agent may be present in respiratory tract specimens (sputum, pleural fuid, bronchoscopy specimens, lung tissue), and in extrapulmonary sites. Laboratory Safety and Containment Recommendations the organism may be present in urine, blood, and tissues of infected animals and humans. Ingestion, accidental parenteral inoculation, and direct and indirect contact of skin or mucous membranes, particularly the conjunctiva, with cultures or infected tissues or body fuids are the primary laboratory hazards. Gloves should be worn to handle and necropsy infected animals and to handle infectious materials and cultures in the laboratory. Listeria monocytogenes Listeria monocytogenes is a gram-positive, non-spore-forming, aerobic bacillus; that is weakly beta-hemolytic on sheep blood agar and catalase-positive. It may also be isolated from symptomatic/asymptomatic animals (particularly ruminants) and humans. In pregnant women, Listeria monocytogenes infections occur most often in the third trimester and may precipitate labor. While ingestion is the most common route of exposure, Listeria can also cause eye and skin infections following direct contact with the organism. Gloves and eye protection should be worn while handling infected or potentially infected materials.