PANDEMICS
| EMERGING INFECTIOUS DISEASES AND THE UPCOMING PANDEMIC— David J. Karras, MD, Professor of
Emergency Medicine, Associate Chair for Academic Affairs, and Research Director, Department of Emergency Medicine,
Temple University School of Medicine, Philadelphia, PA
|
| Historical overview: 1950 to 1990 (era of complacency)—increasing use of antibiotics and vaccines (polio vaccine
developed); public sanitation improved; clinical epidemiology became science; Centers for Disease Control and Prevention
(CDC) founded; federal funding of local and state public health agencies began; 1990s (new era of plagues)—new
pathogens appear; microbes develop resistance to commonly used antibiotics; rapid transit of food and people accelerates
spread of infectious disease; bioterrorism appears; plagues fueled by—negligent antibiotic use by physicians, patients,
and in livestock; public complacency and high-risk behaviors; overwhelmed public health systems; questionable ability
to respond to natural disasters and epidemics
|
Methicillin-Resistant Staphylococcus aureus (MRSA)
| Nosocomial MRSA: identified in 1960s; risk factors—hospitalization or residence in long-term care facility; use of antibiotics;
dialysis; chronic disease; intravenous (IV) drug abuse
|
| Community-acquired MRSA (CA-MRSA): Herold et al 1998—retrospective study at pediatric hospital; found
prevalence of CA-MRSA 10 per 100,000 admissions in period 1988-1990 (13% with no traditional risk factors), increased
to 259 per 100,000 admissions during 1993-1995 (71% with no risk factors); reports of CA-MRSA outbreaks—
in day care centers, football and other sport teams, and prisoners
|
| Study (2005): 1600 cases of CA-MRSA in 3 communities over 2 yr (8%-20% of all MRSA isolates); risk factors age <2
yr and black ethnicity; no traditional MRSA risk factors; 87% of cases skin and soft tissue infections; 4% urinary tract infections
(UTIs); 4% sinus infections; 3% bacteremia; 2 cases of meningitis; 1% of cases osteomyelitis, bursitis, and arthritis;
antibiotic susceptibility—100% to vancomycin, 96% to linezolid, 97% to trimethoprim-sulfamethoxazole
(TMP-SMZ); 87% sensitivity to clindamycin; tetracycline sensitivity ≈80%
|
| Risk factors for CA-MRSA: young age; minority ethnicity; lower household income; skin and soft tissue infections
and noninfectious disease; 24% of adults and 85% of children have no risk factors
|
| CA-MRSA in emergency department (ED) patients (Moran et al): overall, 55% of study patients had
MRSA; MRSA found in 61% of abscesses, 53% of infected wounds, and 47% of cellulitis; antibiotic susceptibility—
95% sensitivity to clindamycin, 100% to TMP-SMZ and rifampin
|
| Implications for emergency medicine: patients with uncomplicated abscesses need incision and drainage (I and D;
antibiotics needed only if extensive cellulitis present); closer follow-up required for those who do not respond to I and
D or to appropriate antibiotics; prudent to routinely do wound checks for patients with skin and soft tissue infections;
prudent to routinely culture even uncomplicated infections (guides therapy if patient becomes worse; helps hospital
and local health department determine prevalence of MRSA in community)
|
 | When antibiotics indicated: if prevalence of CA-MRSA low in area, no change in antibiotic therapy, ie, first-generation
cephalosporin; in communities with high prevalence of CA-MRSA—TMP-SMZ drug of choice (may add rifampin
for synergy); clindamycin for patients allergic to sulfonamides (efficacy decreasing); doxycycline (efficacy fading); use
vancomycin if patient to be admitted
|
| Caveats: Streptococcus pyogenes most common organism in uncomplicated cellulitis, and TMP-SMZ not best drug for
this organism; addition of first-generation cephalosporin recommended for severe cellulitis or abscess complicated by
cellulitis; clindamycin resistance may develop over time, especially in patients resistant to erythromycin; health care
workers—need not worry about carrying MRSA home; low incidence of autoinoculation or transmission to first-generation
contacts
|
Influenza A (H5N1; Avian flu)
| Natural history: normally circulated in wild birds and transmitted via their stool; occasionally infects domestic bird livestock,
causing 90% mortality; routinely controlled by destroying birds; outbreaks usually occur in Asia because of antiquated
poultry handling and delivery methods; humans rarely infected (≈100 cases worldwide), despite millions of
infected birds; human-to-human transmission extremely rare, and second-generation transmission does not occur
|
| Reasons for concern: infection highly fatal; influenza viruses mutate rapidly by random exchange of groups of genes
with other viruses (reassortment); if avian flu virus acquires genes from human influenza virus that enable it to be transmitted
from human to human, global pandemic likely; World Health Organization (WHO) states that avian flu becoming
disease of humans matter of “when,” not “if”
|
| Pandemic: defined as global infection by new pathogen or strain of pathogen to which humans have no natural immunity;
3 conditions required—1) emergence of new virus or viral subtype; 2) ability to cause serious disease in humans; 3)
ability to spread easily among humans; first 2 conditions already exist, only third required for start of pandemic; 20th
century pandemics—Spanish flu (1918) caused 500,000 deaths in United States; Asian flu (1957) 70,000 Americans
died; Hong Kong flu (1968) 34,000 Americans died; these were all avian influenzas; current data—winter of 2005 to
2006, 108 cases of avian flu, resulting in 51 deaths; at present, world at 3 on WHO 6-point “scariness chart” (pandemic
alert)
|
| United States government projections: if pandemic occurs, 90 million people will be infected; moderate
pandemic—800,000 will require hospitalization; >100,000 people will require intensive care unit (ICU) care, 65,000
on ventilators; ≈200,000 deaths; severe epidemic—10 million people will require hospitalization; 1.5 million people
will need ICU care, almost 1 million on ventilators; ≈2 million deaths
|
| Budget: total $7.1 billion; $3 billion to develop new vaccine; $1.5 billion to purchase existing vaccines; $1 billion to
stockpile antiviral drugs; $1 billion to develop new treatments and vaccines
|
| What government expects of EDs: develop planning and decision-making structures; develop written plans to address
disease surveillance and hospital communications; participate in response drills; estimate minimum number of
necessary personnel and determine how staffing needs will be met (eg, reassign administrators; enlist volunteers,
health care students, patients’ families; recruit retired personnel); suggested stockpiles—antiviral agents; medications
for respiratory failure; masks; ventilators
|
| When pandemic begins: activate enhanced staffing plan; move other inpatients to other facilities; continue to provide
usual medical care
|
| Clinical characteristics of avian flu: affects previously healthy individuals; most cases in young adults and children,
but older and chronically ill people more vulnerable if exposed; incubation period 2 to 4 days; symptoms—fever, chills,
cough, watery diarrhea; at 5 days, viral pneumonia develops, with patchy multifocal infiltrates, often consolidation;
within 1 wk, death from acute respiratory distress syndrome (ARDS); overall death rate ≈50%; almost universally fatal in
younger patients
|
| Treatment: virus resistant to amantadine and rimantadine; neuraminidase inhibitors, eg, oseltamivir (Tamiflu) and zanamivir
(Relenza) effective against influenza A and B; when started within 48 hr of symptom onset, result in 2- to 4-day
reduction in symptom duration in influenza A; all strains of 2004 avian flu susceptible to oseltamivir; however, resistant
strains reported in Asia, resulting in 2 deaths
|
| Prophylaxis: regular flu vaccine not effective against avian flu; virus poorly immunogenic, and no vaccines being developed;
oseltamivir 70% to 90% effective in preventing infection; oseltamivir—expensive; proprietary; complex manufacturing
process; will take years to make enough drug for worldwide pandemic; currently in short supply because of
stockpiling by WHO and United States government
|
| Implications for EDs: respiratory hygiene and cough etiquette—patients who present with secretion-producing respiratory
illness put into separate waiting room and told to cough into tissue and wash hands frequently; provide receptacles
for tissues; triage—identify high-risk patients, ie, those who have recently traveled to high-risk areas and have
fever and respiratory complaints; ask about expanded risk factors, eg, exposure to someone who has recently returned
from high-risk area and has respiratory illness; isolate patients with flu-like illnesses; treatment areas—maintain isolation
and hygiene; confirm history; perform influenza A testing for high-risk patients; those who test positive should be
admitted, placed in respiratory isolation, and reported to CDC or local health agency; start anti-influenza therapy; precautions
for staff—hand washing most important; contact isolation; use dedicated equipment; eye protection when
within 6 ft of patients; negative-pressure rooms and N-95 fitted respirators; postexposure prophylaxis—oseltamivir (effective
regimen unknown for avian flu; 75 mg once daily for 7-10 days recommended)
|
| WHAT YOU NEED TO KNOW ABOUT THE AVIAN FLU —Joseph C. Howton, MD, Medical Director, Emergency
Services, Portland Adventist Medical Center, Portland, OR
|
| Transmission of H5N1: ingestion of undercooked infected poultry and eggs; slaughtering of poultry in open-air markets;
water contamination by asymptomatic infected ducks; human-to-human transmission?
|
| Case of fatal H5N1 flu in children: boy 4 yr of age presented with encephalitis and no respiratory complaints; sister
9 yr of age died 2 wk earlier; autopsy found virus in cerebrospinal fluid (CSF), serum, throat, and feces (enormous public
health implications; regular flu does not spread in feces)
|
| Pathogenesis: incubation period—infected patients contagious but asymptomatic and afebrile for ≈24 hr, making effective
quarantine difficult; ordinary flu—self-limited infection of upper respiratory tract; secondary viral or bacterial
pneumonia occasionally develops; highly pathogenic avian influenza (HPAI)—exhibits pantropism, ie, severe gastroenteritis,
encephalitis, pulmonary hemorrhage, other nonrespiratory involvement; clinical presentation of HPAI (10
patients)—average age 14 yr; incubation period 2 to 4 days after exposure; all presented with fever, shortness of breath,
and cough; 5 produced sputum (blood-tinged in 3); 7 had diarrhea; none had pharyngitis, runny nose, or rash; all had abnormal
chest x-ray on admission, with bilateral infiltrates; all lymphopenic, 9 thrombocytopenic; all received antibiotics;
8 died; 5 received oseltamivir (probably late in course; 4 of these died); reasons for high mortality—virus induces massive
release of cytokines (cytokine storm) into affected tissues, compounding injury; younger healthier immune systems
may overreact
|
| Diagnosis of HPAI: if suspected in high-risk patient, use throat swab, not nasopharyngeal swab; obtain rapid flu test; if
type A, send to biosafety level 3 laboratory for viral culture and determination of subtype and serology
|
| Treatment: oseltamivir—to be effective, must be given within 48 hr of symptom onset (standard dose 75 mg/day for 5
days); effectiveness in HPAI unclear; resistant strains reported, but these not easily transmitted; studies in mice indicate
higher doses and longer treatment may be needed, eg, 150 mg bid for 10 days; prophylaxis of first responders not option
because of shortage of oseltamivir; no contraindications (main issues cost and availability); probenecid may enhance bioavailability
of oseltamivir; zanamivir—inhaled neuraminidase inhibitor; contraindicated in patients with reactive airways
disease, eg, asthma; other agents—no randomized trials on ribavirin, steroids, or interferon, but case series indicate lack
of effectiveness; alternative therapies—2 high-quality randomized trials on regular influenza A indicate effectiveness of
Sambucol (derived from elderberry [sambucus nigra]); symptom duration reduced to 2 to 3 days from 6 days; safe for any
age group and in pregnancy; widely available in health food stores; oscillococcinum of no value
|
| Vaccines: would take ≥6 mo to produce vaccine specific for pandemic strain; vaccine produced before pandemic unlikely
to be effective; could produce only enough vaccine for frontline workers; H5N1 has low immunogenicity, so large
amounts of virus needed to make vaccine using current antiquated manufacturing techniques; vaccination of poultry
daunting task; poultry vaccine low dose and too contaminated for human use
|
| Protecting health care workers: mask for patient; place patient in negative-pressure room; N-95 mask or powered
air-purifying respirator (PAPR) for workers; gowns, gloves, eye protection, and dedicated equipment; be vigilant for febrile
illness in workers within 1 wk of possible exposure
|
| Preparation: hospitals—Department of Health and Human Services (HHS) recommends written plan addressing use of
vaccines, antiviral drugs, ventilators; exercises and drills; home—anticipate food shortages, interruption of power and
water supplies (due to sick workers); N-95 masks and hand sanitizers
|
| Phases of pandemic (WHO): officially in phase 3, unofficially in phase 4; phases 1 and 2—interpandemic period;
phase 3—transmission of potential pandemic threat from birds to humans, with rare human-to-human transmission;
phase 4—clusters of cases suggest limited unsustained human-to-human transmission; phase 5—larger clusters of
cases but human-to-human transmission not sustained; phase 6—sustained human-to-human transmission (pandemic
under way)
|
| More on preparation: HHS recommends at phase 4, need food and water for ≥3 wk; personal medications for 3 mo; 55-
gal water barrel; dehydrated foods, grains; communication devices, including hand-cranked radios, cell phones with text
messaging; required reading—“The Great Influenza” by John Barry; “Woodson Pandemic Handbook” at www.birdflumanual.com
|
| Final thoughts: cell culture method for vaccine production could decrease manufacturing time to 2 to 4 mo (1 to 2 yr
away); need enhanced syndromic surveillance and more hygienic poultry farming; have ethical discussions about, eg,
ventilator allocation, before outbreak
|
Educational Objectives
| The goal of this program is to educate the listener about emerging infectious diseases such as community-acquired methicillin
resistant Staphylococcus aureus (CA-MRSA) and the possibility of an avian influenza pandemic. After hearing and assimilating
this program, the clinician will be better able to:
|
| 1. List the differences between nosocomial MRSA and CA-MRSA, including risk factors, affected age groups, types of
infections and emergency department (ED) management.
|
| 2. Describe the United States government’s projections about a possible avian influenza pandemic and what the government
expects from EDs in such a pandemic.
|
| 3. Discuss the implications of a possible avian influenza pandemic for EDs, including triage, isolation of patients, and
protection of health care workers.
|
| 4. Describe the pathogenesis, diagnosis, and treatment of avian influenza.
|
| 5. List the phases of a pandemic as described by the World Health Organization (WHO) and some suggested measures
to be taken by private individuals as well as hospitals to prepare for a pandemic.
|
Discussed on This Program
Amantadine HCl [Symmetrel]
Clindamycin (several trade names and formulations)
Doxycycline (several trade names)
Erythromycin [Akne-Mycin, A/T/S, Emgel, Eryderm 2%, Erygel, Ery Pads, Ilotycin]
Interferon alfacon-1 [Infergen]
Linezolid [Zyvox]
Oseltamivir phosphate [Tamiflu]
Probenecid
Ribavirin [Copegus, Rebetol, Ribospheres, Ribatab, Virazole]
Rifampin (rifampicin) [Rifadin, Rimactane]
Rimantadine HCl [Flumadine]
Sambucol [Sambucus nigra]
Tetracycline HCl [Sumycin 𣝢’, Sumycin 𣡜’, Sumycin Syrup]
Trimethoprim-sulfamethoxazole (co-trimoxazole; TMP-SMZ; several trade names)
Vancomycin [Vancocin, Vancoled]
Zanamivir [Relenza]
Suggested Reading
Avalos-Mishaan A et al: Severe Staphylococcal sepsis in adolescents in the era of community-acquired methicillin-resistant
Staphylococcus aureus. Pediatrics 115:642, 2005; Bartlett JG: Planning for avian influenza. Ann Intern Med
145:141, 2006; Epub 2006 Jun 26; Beigel JH et al: Avian influenza A (H5N1) infection in humans. N Engl J Med
353:1374, 2005; Dietrich DW et al: Community-acquired methicillin-resistant Staphylococcus aureus in southern New
England children. Pediatrics 113:e347, 2004; Fabain N: A special report--what is the threat and why should we be concerned?
J Environ Health 68:46, 2006; Ferguson NM et al: Public health. Public health risk from the avian H5N1 influenza
epidemic. Science 304:968, 2004; Herold BC et al: Community-acquired methicillin-resistant Staphylococcus
aureus in children with no identified predisposing risk. JAMA 279:593, 1998; Jeyaratnam D et al: Community associated
MRSA: an alert to paediatricians. Arch Dis Child 91:511, 2006; John CC et al: Therapies and vaccines for emerging
bacterial infections: learning from methicillin-resistant Staphylococcus aureus. Pediatr Clin North Am 53:699, 2006;
Johnigan RH et al: Community-acquired methicillin-resistant Staphylococcus aureus in children and adolescents:
changing trends. Arch Otolaryngol Head Neck Surg 129:1049, 2003; Kaiser J: Public health. Pandemic or not, experts
welcome Bush flu plan. Science 310:952, 2005; Liu JP: Avian influenza--a pandemic waiting to happen? J Microbiol
Immunol Infect 39:4, 2006; Luke CJ et al: Vaccines for pandemic influenza. Emerg Infect Dis 12:66, 2006; Mermel
LA: Pandemic avian influenza. Lancet Infect Dis 5:666, 2005; Moran GJ et al: Methicillin-resistant S. aureus infections
among patients in the emergency department. N Engl J Med 355:666, 2006; Moran GJ et al: Methicillin-resistant
Staphylococcus aureus in community-acquired skin infections. Emerg Infect Dis 11:928, 2005; Normile D et al: Infectious
diseases. Lapses worry bird flu experts. Science 308:1849, 2005; Normile D: Avian influenza. Europe scrambles to
control deadly H5N1 Strain. Science 310:417, 2005; Perez DR et al: Avian influenza: an omnipresent pandemic threat.
Pediatr Infect Dis J 24:S208, 2005; Smith DJ: Predictability and preparedness in influenza control. Science 312:392,
2006; Stephenson I: Are we ready for pandemic influenza H5N1? Expert Rev Vaccines 4:151, 2005; Trampuz A et
al: Avian influenza: a new pandemic threat? Mayo Clin Proc 79:523, 2004; Tsang KW et al: H5N1 influenza pandemic:
contingency plans. Lancet 366:533, 2005; Webby RJ et al: Responsiveness to a pandemic alert: use of reverse
genetics for rapid development of influenza vaccines. Lancet 363:1099, 2004; Winterfeld A et al: Preparing for a pandemic:
concern over a possible avian flu pandemic is moving states, communities, and the federal government to action.
State Legis 32:14, 2006; Wong SS et al: Avian influenza virus infections in humans. Chest 129:156, 2006.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial relationship
with the manufacturer or provider of any commercial product or service discussed. For this issue, the faculty reported
nothing to disclose.
Dr. Karras spoke at the 12th Anuual Scientific Assembly of the Amercian Academy of Emergency Medicine, February
16-18, 2006, in San Antonio, TX. Dr. Howton was recorded May 15, 2006 in Sonoma, CA, at the 2006 CEP CME
Southern Regional Meeting, sponsored by the California Emergency Physicians Medical Group. The Audio-Digest
Foundation thanks the speakers and the sponsor for their cooperation in the production of this program.
|
