4 February 2006 1 TIBDN T O R O N T O I N V A S I V E B A C T E R I A L D I S E A S E S N ETWORK Volume 4, Issue 1 T ORONTO Use of antiviral medication and stockpiling Issues Karen Green RN, MSc I NVASIVE B ACTERIAL ISEASES Vaccines are always the best protection strategy’s effectiveness depends on (ii) Individual stockpiling may result in D N ETWORK from , but it is unlikely that a the ability to quickly identify cases inappropriate use of the medications. TIBDN vaccine against the new pandemic strain and their contacts, since the generation of influenza will be available during the time of influenza (average time from So we are faced with the dilemma. It Pandemic influenza update Allison McGeer, MD early stages of a pandemic. During this onset of symptoms in one case to onset is clear that individuals are better off period, the use of antiviral medication in the second case) is only 2 days. with a stockpile, but it is also clear In January, 2006, the first A/H5N1 influenza cases outside of Southeast Asia were must be carefully evaluated. For the foreseeable future, there are that society is better off if the supply is reported from Turkey. The bad news is that this virus has rapidly become widespread in insufficient supplies of neuraminidase centralized. In addition, there is a lack wild waterfowl and chickens throughout Turkey. There may be as many as 30 human Antiviral medications effective against inhibitors to attempt this strategy. of consensus about what an optimal cases, still with a high mortality rate. The hemagglutinin protein of the viruses isolated current influenza strains are effective stockpile size is, with some physicians from Turkey has changes that make it closer to a human virus than ever before. The against pandemic strains in vitro, Treatment believing that currently planned good news is that there has been no human to human transmission identified in Turkey, and will likely provide substantial There is good evidence that early Canadian government stockpile sizes and that control measures being implemented there seem to have been effective in protection. Resistance is a potential treatment with oseltamivir is (enough to treat 10% of the population) slowing the number of new human cases. issue, but is unlikely to be a significant effective in reducing the duration are too small. problem for the next few years. There and severity of influenza, and the risk Our knowledge about influenza viruses and influenza infection is growing rapidly. are drawbacks to the use of antiviral of serious complications, including Thus, physicians have found Nonetheless, it remains impossible to predict whether H5N1 will be the cause of the medication. Antivirals only provide hospitalization. It seems likely that themselves bombarded with requests next pandemic. We do know that the time to the next pandemic gets shorter every day, protection while a person is taking treatment of pandemic influenza will for oseltamivir prescriptions. In and our chronic shortages in health care combined with our “just-in-time” delivery them. Thus, if antivirals run out before also be effective. Early treatment is the absence of clear directives or system will mean that even a mild pandemic will severely stress the system. � a vaccine is available, everyone is at more effective than later treatment, so recommendations on how to respond risk, and the pandemic impact may attempts will be made to start everyone to these requests, physicians find Both Health Canada and the Ontario Ministry of Health will be releasing new versions only be delayed. Long term use might with compatible illness on therapy themselves in a struggle between their of their pandemic plans later this spring. Many local health units have first versions of also have side effects that we have within the first 48 hours after symptom responsibility to their patients and their their plans, and most hospitals are also working on plans. It is also time for physician not yet identified. There are several onset. There is no doubt that this will be responsibility to the public good. In offices, pharmacies, and clinics to start preparing. While the Ontario Ministry of ways that antivirals may be used in a difficult, since so many people will be the fall of 2005, Roche decided to stop Health is building stockpiles of personal protective equipment, they are expecting that pandemic. ill simultaneously. Additional problems sales to private pharmacies in North INSIDE THIS ISSUE individual offices and hospitals will also contribute to their own protection. A list of with this strategy are that treatment for America. In late January, this ban was supplies that offices and clinics should consider stockpiling is shown in the box: each Continuous prophylaxis influenza is much less effective than lifted in the United States, but not in office should have enough to manage for 4-6 weeks. Clinics should also consider how Use of antiviral medication by prophylaxis, and many treated people Canada. PAGE they will separate influenza patients from non-influenza patients (it may be a good idea uninfected individuals for the duration will likely get complications. At the to consider “shared” clinics or triage sites in cooperation with local hospitals and , where physicians and other staff contribute hours), and how to start providing of influenza activity (probably 50-100 moment, government stockpiles are The best each of us can do is to offer 1 Pandemic influenza update � days) is an effective option, but one that targeted to treatment of 10% of the ‘credible’ explanations to patients patient teaching about preventive practices and home management of influenza. requires large stockpiles. This option is population at currently recommended seeking drugs for personal stockpiles. 2 What’s new in seasonal influenza? not feasible for the general population, doses. It is estimated that about 35% Patients are rational in wanting their Pandemic Influenza Planning because such supplies cannot be of people will develop influenza, and own stockpile and society is rational in 2 Laboratory confirmed Suggested supply list obtained; it is also not cost-effective likely that higher doses and longer not wanting them to have it. As long influenza illness requiring for offices and clinics Canadian Pandemic Influenza Plan: hospital admission: Clinical http://www.phac-aspc.gc.ca/cpip-pclcpi in most pandemic scenarios. Long- duration of therapy will be needed for as oseltamivir remains in short supply, features, treatment, and Alcohol handwash term prophylaxis may be beneficial pandemic influenza. Our stockpiles there is only one really legitimate outcomes Fluid resistant masks Ontario Health Plan for an Influenza Pandemic: Eye protection http://www.health.gov.on.ca/english/providers/ in groups in whom minimizing for therapy are still inadequate if the argument against personal antiviral 4 Use of antiviral medication (eg. 2 pairs safety glasses program/emu/pan_flu/pan_flu_plan.html absenteeism during a pandemic is pandemic is moderate or severe. stockpiles. That is, that society as a and stockpiling issues per person) critical, eg. healthcare professionals. whole will be better off if the entire Gloves Pandemic Influenza Plan: Surface cleaning supplies http://www.toronto.ca/health/pandemicflu Individual Stockpiling versus supply is centrally controlled for Re-useable thermometer Postexposure prophylaxis Government Stockpiling optimal use. In order to support this Public Safety Canada: Close contacts of an individual with Public health stockpiling of anti-viral argument, however, each of us needs http://www.safecanada.ca/pandemic influenza could be treated with antiviral drugs for an influenza pandemic is to be educated about the potential medication after exposure but before viewed as an appropriate and cost- uses of oseltamivir, to make a decision This newsletter has been generously the onset of symptoms. This strategy, effective strategy. The disadvantages about what the size of our stockpiles sponsored by an unrestricted Editor: Mount Sinai Hospital, Room 1460 educational grant from: Karen Green, RN, MSc Toronto, ON, M5G 1X5 if used in conjunction with immediate of individual stockpiling are: should be for Canada, and to lobby our Toronto Invasive Bacterial Diseases Network 416-586-3124 isolation of the ill person, might reduce (i) When shortages exist, centralized professional organizations, local public transmission once a case has been decision making gives us the best health units, and governments to ensure This newsletter is a publication of the Toronto Invasive Bacterial Diseases Network (TIBDN), a collaboration of the microbiology laboratories, infection control practitioners, and public health officials who serve the population identified, and permit close contacts chance of allocating drug in a way that that these stockpiles exist. of Metropolitan Toronto, Peel, York, Durham, Simcoe, Hamilton, and Halton Regions. For an electronic copy of to care for that person at home. This minimizes mortality and morbidity; this newsletter please visit our website at: microbiology.mtsinai.on.ca/tibdn 2 3 TIBDN T O R O N T O I N V A S I V E B A C T E R I A L D I S E A S E S N ETWORK http://microbiology.mtsinai.on.ca/tibdn

What’ s new in seasonal influenza? Allison McGeer, MD A case of influenza requiring hospital in hospitals and nursing homes, but community-acquired illness had a test is positive. admission is defined as a patient because diagnostic testing is done more physician visit before their admission. Although much of our attention is years vaccine will not be very effective whose illness requires hospitalization, commonly in these circumstances. Twenty-four percent of patients were Physicians should also think about focused on when the next influenza against. Those people who have had a and who has a positive antigen test started on an antibiotic, while less than replacing empiric antibiotics with pandemic will emerge, annual vaccine in previous years will likely or a culture yielding influenza A. Overall, none of the 102 children, and 1% were started on antiviral therapy empiric antivirals when out-patient epidemics of influenza continue still have substantial protection. Patients who acquire influenza while 112 of 289 adults (39%) were treated therapy of respiratory illness is to cause thousands of deaths and in hospital are also included. Clinical with oseltamivir. Oseltamivir was Comments being initiated during influenza hospitalizations in Canada. The other significant change this year data is collected by chart review, and prescribed more often to patients with These data illustrate that, despite that season. Although we tend to think of has been the emergence of resistance interview with patients, attending and nosocomial and nursing home acquired more than 40% of people in Ontario using antibiotics in patients we are Last year’s influenza season began to amantadine in influenza A/H3N2 family physicians. disease (P<.001), older patients receive influenza vaccine every worried about to protect them from early in January in Ontario, with viruses. Amantadine resistance (median age 78y vs 57y, P<.001), and year, influenza is still an important complications, the data from TIBDN During the 2004/5 influenza season, activity peaking in the first week of emerges quite easily in patients patients with chronic underlying illness disease. Current vaccines substantially surveillance suggests that antivirals 403 patients were hospitalized due to February. Most influenza was due to who are on treatment for influenza; (38/114 with Charlson scores of >2 vs reduce the mortality associated with may actually be more effective at lab-confirmed influenza. Thus, during A/H3N2, and a mid-season shift in however, it has remained otherwise 50/ 275, P=.002). influenza (for adults over the age of preventing serious complications and the virus meant that most infections rare until very recently. In Canada, the first five months of 2005, more 65, vaccination is associated with hospitalization. patients were hospitalized for lab- in February and March were caused until 2003, all isolates of influenza A Current recommendations are that 42% reduction in all cause mortality confirmed influenza than for invasive by a new variant called A/H3N2/ were susceptible to amantadine (note: antivirals should only be initiated during influenza season). However, Finally, 13% of influenza cases pneumococcal disease. There was a California/7/2004. Fortunately, there influenza B is intrinsically resistant). within 48 hours of the onset of there is enough residual disease that identified by surveillance were hospital great deal of variability in the number was sufficient cross-reactivity between However, amantadine resistance has symptoms: in this cohort, most patients better diagnosis and treatment remain acquired, and two of 59 patients with of diagnosed cases per hospital: this new strain and the H3N2 strain in now emerged and spread rapidly, This were treated later. Only 13/54 (24%) important. hospital-acquired influenza died from hospitals rarely doing NP swabs the vaccine (A/Fujian/411/2002) that year, more than 90% of the influenza adults with community-acquired their infection. The identified rate of identified few cases: the two hospitals the vaccine still provided protection. A isolates tested in Canada have disease, 9/22 (41%) with nursing home These data confirm data from hospital acquired influenza in TIBDN routinely testing adults with respiratory Some experts believe that the apparent been resistant to amantadine. Both acquired disease, and 20/36 (55%) randomized controlled trials that last year was still 5 to 10 times lower illness (Credit Valley and William increase in the speed of evolution of Health Canada and the US Centers for with nosocomial disease had their first oseltamivir therapy is associated with than that identified in other prospective Osler Health Centre) diagnosed 221 new virus strains presages the next Disease Control and Prevention have dose of oseltamivir within 48 hours of a very significant reduction in serious studies where testing was routine, and 82 cases, respectively. pandemic. recommended that only neuraminidase symptom onset. Nonetheless, treatment complications and mortality due to suggesting that our detection of inhibitors (oseltamivir and zanamivir) with oseltamivir appeared to be influenza. Further, they suggest that if hospital-acquired influenza cases is So far this year, there has been little be used for treatment or prophylaxis of Of the 403 patients, 102 (25%) were associated with a substantial reduction a patient is shedding virus at admission poor. Most patients at risk of acquiring influenza activity in Ontario. Most influenza. children (aged 15 years of age and in mortality. In multivariate analysis, (that is, has a positive rapid antigen influenza in the hospital are elderly and influenza to date in Canada has under), 73 (18%) were adults aged 16- factors associated with survival were test), treatment is effective even if the have comorbid illnesses. Such patients occurred in Alberta and BC. In Alberta, 64 years of age, and 228 (57%) were younger age (OR 4.1, 95% CL 1.1,15), patient has been symptomatic for more are also likely to benefit from early than 48 hours. During influenza season, antiviral therapy. During the influenza most isolates have been influenza B, Laboratory confirmed adults over the age of 65 years. residence in the community rather and several school outbreaks have been all patients who require admission season, we should be alert to hospital influenza illness requiring than a nursing home (OR 4.9, 95% Cl reported. In contrast, in BC, most of the Most infections, 291 (78%), were 1.8,14), and therapy with oseltamivir and have symptoms of respiratory –acquired respiratory disease in hospital admission: Clinical infections have been influenza A/H3N2 due to influenza A, with 112 (22%) to (OR 3.1, 95% CL 1.03,10). infection should have a rapid test done patients, test them promptly, and treat (so far, all the A/California/7/2004 features, treatment, and influenza B. Influenza B infection was for influenza, and should be treated those patients who have influenza. strain). outcomes more common in children (50/102, More than half (53%) of patients with with oseltamivir (or zanamivir) if the Allison McGeer, MD 49%) than adults aged 15-64 years Over the last few years, two different (21/73, 28%), or older adults (41/228, Table 1: Clinical characteristics of patients with LCII requring hospitalization Table 2: Treatment & outcomes of patients with LCII requiring hospitalization groups of influenza B strains have It is important before the pandemic 18%), P<.001. that we understand as much as 0-14 years 15-64 years 65+ years Adults evolved. For the last few years, the (n=102) (N=73) (N=228) Children Community Nursing Home Hospital major influenza B strain has been of possible about the clinical features Clinical characteristics, treatment Source (N=102) (N=181) (N=50) (N=58) and complications of influenza, as Underlying illness the “Shanghai” lineage, with a smaller and outcomes of disease are shown None 77/101 (76%) 31/72 (43%) 32/220 (15%) Antiviral treatment number of isolates of the “Hong Kong” well as the impact of treatment with in Tables 1 and 2. Most children and Lung disease 17 (17%) 22 (31%) 83 (38%) Amantadine 0 1 (0.6%) 1 (2%) 0 lineage. The 2003 and 2004 vaccines antivirals. For this reason, the Toronto nearly half of adults aged 50-64 years Diabetes mellitus - 17 (24%) 108 (49%) Oseltamivir 0 54 (30%) 22 (44%) 36 (62%) Invasive Bacterial Diseases Network Cardiac disease 1 (1.0%) 8 (11%) 149 (68%) had antigen from the Hong Kong type of age had no significant underlying Renal disease - 8 (11%) 29 (13%) Antibacterial treatment 75 (74%) 146 (81%) 46 (92%) 35 (60%) viruses; because the Shanghai type (TIBDN) has begun population-based illness; however, more than 25% of Cancer 2 (2.0%) 3 (4.2%) 24 (11%) surveillance for laboratory-confirmed Other 4 (4.0%) 7 (9.7%) 8 (3.6%) ICU Admission 2 (2%) 27 (15%) 9 (22%) N/A viruses were increasing in frequency, adults aged 15-64 years were smokers. Current smoker - 20/72 (28%) 15/220 (6.8%) the 2005 vaccine antigen was changed influenza illness (LCII) resulting in A very significant proportion of Source of infection Hospital LOS 2 (1-10d) 6 (1-103d) 10 (1-47d) N/A to a Shanghai like one. However, this hospital admission in residents of our infections were acquired in nursing Community 101 (99%) 57 (78%) 135 (59%) (median, range) population area (metropolitan Toronto Nursing home - 4 (6%) 47 (21%) year so far, most of the B viruses have homes, or in the hospital – this is not Acute care hospital 1 (1%) 12 (16%) 46 (20%) Death due to influenza 0 12 (6.6%) 9 (18%) 3 (5.2%) been Hong Kong-like strains that this and the regional municipality of Peel) because influenza is more common

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