The Dental Forum

November 10, 2006

Avian Flu And Virology

Dr. Dennis Maki

Meeting Minutes

37 members, 8 guests, 1 life member

 

 

Dr. William Dowsett introduced our speaker, Dr. Dennis Maki at 8:50 a.m.  He is the Director of Infectious Disease, Department of Medicine, UW-Madison.

 

“Advances in the Control of Infectious Disease in the 20th Century”

 

 

Advances in Control of Infectious Disease

Dr. Maki gave an Historical review- from Pasteur  to Prions. 

                         

 

 . Dr. Maki likes to study infectious disease because we can identify cause of disease.  Diseases are managed at cellular level.  Toxin for tetanus denatured and vaccine made.   Infectious disease spans all disciplines of medicine; it is multi-disciplinary.  We can prevent disease.  He sites effect of epidemiology –infection control prevention measures -and antibiotics on decline in crude mortality rates in U.S.  Polio is a significant example.  95-8% or diseases have antiinfective.

 

 Impact of Epidemiology on Public Health  - Decline of mortality in 20-21st centuries due to epidemiology

            -T.B.-control, screening, preventing spread, before vaccine

            -More TB in immigrants

Impact of anti-infective therapy-

-        Pneumonia- 5% mortality   

-        Meniningities- 5% mortality

-        Endodocarditis- 75-95% survive due to antibiotic

-        Septic Shock-75% survive

Impact of Vaccines- Smallpox has killed more individuals than any other disease.  Vaccine was huge achievement.  Russia, US led immunization campaign. The last case was 1977.  Immunization is the greatest health achievement in 20th century.

Diptheria, Tetanus, Pertussis, Polio, Measles, Rubella, H influenzae meningitis all positively affected by vaccines. 

 

Immunization should continue. A test of this was during  Glasnost in Russia- no taxes, no immunization. In  1989, when the immunization program stopped,  from less than 100 to 50000 children were affected by diphtheria.  The Pertussis vaccine has side effects, but saves countless lives.  As Japan economy became able provide vaccine, cases dropped to less than 1000 from rumors of  80,000. The day we stop using vaccines we will see the quick return of disease.

 

 

 

Recommended vaccines for over 40 health care workers.

            1.Tetanus diphtheria booster every 10 years

            2.Acellular pertussis vaccine for adult health care works

            3.HPV vaccine for cervical cancer-

4.MMR- most of us need second dose of vaccine, if you have not had meas,     mumps

            5.Hep A for travel, Hep B in children

            6.PERTUSSIS IMP

            7.PNEUMONIA

 

Moderation of inflammation of disease- we are seeing success

 

A. Pneumococcal meningitis- study demonstrated that modest dose of anti-inflammatory decreased deaths by 50%. (Corticosteroid less that $20 dose)

B. Trial of addition  rhAPC in Septic Shock syndrome- Added recombinant protein C.  Cut mortality by 20%

C.Impact ability detect emerging infectious diseases- Legionaire’s disease.

            List of 30 new diseases since 1975.

D.HIV is most important of new discoveries.  By early 1990’s, meds which could affect at molecular level were available.  Impact of protease inhibitors is key.  We are starting to see drug resistant HIV.  AIDs is a still a tragedy in underdeveloped countries.  40 million cases exist worldwide today.

E.Emerging vaccine for shingles for adults- valcyclovir, famcyclovir, mega doses of acyclovir.  Post herpetic neuralgia is a terrible pain. 10% of population will have shingles by age 70.  Vaccine will significantly reduce chance of contracting disease. 

 

What do we need- human genome project is helpful. We need vaccines for diseases, and better diagnostics. The public needs to be willing to participate in research.  Treatment is based on experience. This produces altruism and personal benefit.  Every protocol is scrutinized for safety and worthiness.   

 

Crisis in Antimicrobial Resistance-

 

Magnitude of Problem- Literally every community or hospital environment- bacteria are resistant.  (except Strept A and syphilis, which can be treated with penicillin)

 

            Staph aureus infections are the issue

-        Penicillin

-        Penicillin resistant-and other meds

-        1997

-        2002- high level vancomycin resistant –

-        New meds

 

Gram negative also resistant (e.coli,…)

-sulfa no longer used due to resistance

-psuedomonas is problem

-fluoroquinolone- resistant pseudomonas- 30%

 

 

Streptococci- all were susceptible to ampicillin in 1989

                        -now 30% resistant to vancomycin resistant enterococci.

 

Community Acquired Pneumonia

 

The organism with the most concerning trends in resistance is strept pneumococci.  In 1977, resistant strains in Africa spread to Europe.  They reached US in early ‘90s.  These strains are resistant to multiple antibiotics.   These strains have a different mechanism of resistance than for other organisms.  The concern is that the hospital has not been involved in acquiring the disease.  The gene complex that mediates has spread into the community. 

 

Multi-drug resistant t.b. is on the rise, esp. on the rise Asia, Russia, South America.  If one is imprisoned in Russian prison, will get t.b.

 

Does resistance (MRSA)multiple resistant staph aureus a big deal?  Dramatic effect on death rates.  He is seeing more and more sternotomy infections with MRSA.  Wash U. -1 in 3 patients got inadequate antibiotic therapy.  VRE, MRSA may be community or hospital acquired. 

 

Why is this happening?- Darwin’s Survival of the Fittest adaptations. Evolution happens in front of our eyes with resistance process.  Resistant species can transfer genetic info to susceptible bacteria. Plasmid transfer accelerated in presence of antibiotics. 

 

Antibiotic use vs. resistance.  The more antibiotic used, the more resistance.  Today we have vancomycin dependent bacteria.

 

Patients that had little exposure to antibiotics had little exposure to resistant bacteria. 

 

Prevention-

1.     Reduce antibiotic pressue

2.     Improve nosoconial infection control

 

Agricultural Use of Antibiotics

            Impact- increased salmonella and camphylobacter, not others.

            No need for antibiotics in animal food.

 

Surgical- If you give antibiotic 1 hour before incision, cut risk in half to two thirds.  One does only is needed.  Rate of infection is 80% post op in large oral maxillofacial surgeries, if no antibiotic.  One dose of antibiotic lowers it to 10%.  Clindamycin orally or cephalosporin IV is recommended. 

 

25-30 mg prednisone is of concern in immunocompromise.  Less is not of concern

 

 

Oral antibiotics

 Phamocodynamics- Is drug effective against the germs we want to kill.  We have used the MIC to tell to this point.  We need to know about the total amount of efficacy with time- how long above MIC and how high above MIC do we need. 

 

What counts is time above the MIC- must be above MIC at least 50% of the time.  The higher above MIC, the more rapidly you kill the organism.  We apply this by giving the drug more frequently. Pen at least 4X day, amox at least 3X day.

 

TMP-Sulfa- little application to dentistry.

 

Oral Pen VK- 500 mg qid

Pen allergy- ask manifestation of allergy.  Hives, angioedema, swelling, bronchospasm, anaphylaxis.  Use Clindamycin (300-child, 450,600mg for one shot), macrolide.

Amoxicillin- broader spectrum better absorbed, but can cause diarrhea, colitis, thrush

Amoxicilling-Clavulinic Acid- 875 or 2000mg bid- anaerobe and aerobic bacteria

 

Do not use Cephalexin-not effective enough.

 

Clindamycin- for absess- kills anaerobes in mouth. Abscess has low pH.  Clindamycin penetrates right into the abscess.  Extremely effective.  Has been revolutionary for periotonsilar abscess.   Treat until no significant evidence that abscess is present.  150-450 mg tid po.  The downside is diarrhea or colitis.  Treatment for bacterial caused diarrhea or colitis is metronidazole. 

 

Doxycycline- Use for third tier.

 

Erythromycin limited use in dentistry.

 

Telithromycin- new medication, but causes hepatic toxicity.

 

No need for fluoroquinolones in dentistry.  Dentists need to help preserve efficacy by not prescribing.

 

Traveler’s diarrhea- sick for 4-5 days.  Can be treated with fluoroquinolone- one day of diarrhea. New med-Rifamixin 400 mg TID.

 

Community Acquired MRSA- Huge amount

            -New anti-infectives

-Linezolid (Zyvox)-  Oligosaccharide for enterococcus or staph.  If given for more than one week, bone marrow suppression.- $100/day.  Monitor for resistance

-Clindamycin is effective against the majority

-MInocycline or TMP Sulfa (for child

 

            If patient cannot get breath, epinephrine (epi pen) and transport

 

C Reactive Protein- Use macro assay to determine inflammation. Most have CRP of 0 or 1.  If you are wondering if they have osteomylitis, treat until CRP is normalized. 

 

 

Emerging Infectious Diseases-

            Legionare’s Disease

            Toxic Shock Disease

            Early 1980’s- AIDS

About 10 years ago, CDC put together “Emerging Infection” manual- why do pathogens emerge?

                        -Societal events- sexual revolution of 19060-70’s

- changes in health care- immunosuppressive drugs- opportunistic infection

                        - Changes in food preparation

Case Studies

 

Case- 50 year old with sore throat- exudate of pharyngitis.  He just returned from the Ukraine- resurgence of diphtheria now.

 

4 year old acute agitation and confusion-febrile, wide eyed, mumbling, mononuclear neuclocytosis- mumps resurgence of 1000 in Midwest a year ago.  She got encephalitis.  Immunity starts to wane.  We need second dose of vaccine for those who have not had mumps.

 

22 year old – 3 cycles of chemo in treatable testicular cancer. Inflammation around catheter site. Oncologist takes cather out; puts him on keflex. Two seeks latter fever of 100, severe abdominal pain- opened and everything looks normal .   Entire body swollen. Chest xray normal, goes into coma, haeart rapid, 106 fever, abdomine distended. Septic shock; cannot intubate easily, can’t get line in, 10 liters fluid in 2 hours. Asked if you have had diarrhea- pseudomembranous colitis was problem-  white count increased. Colon removed.  Died of multiple organ failure 8 days later.  Unnecessary broad spectrum antibiotic administered.  Physicians did not get a history of diarrhea.

Treatment of colitis is metranidazole.

 

Canada now has lethal C. dificile that are super toxin producers.  7000 cases of C. dificile colitis with 1270 death. 

 

Tell patient that they can have diarrhea- if becoming severe with cramps or fever, so physician immediately! 

 

We adjourned for a delicious holiday turkey dinner!

The group reconvened at 1:10 p.m. to continue hearing Dr. Maki’s lecture.

 

WEST NILE VIRUS

West Nile Virus- 1999- First outbreak in NY

            -Viral meningal encephalitis

            - CIA- got involved with CDC- possible bioterrorism

 

By 2003, West Nile in 46 states- summer/fall disease when mosquitos

-        Subclinical exposure affects blood supply

-        Increased #s of cells in spinal fluid- RNA test in spinal fluid

 

How to prevent? Do not get mosquito bite- use repellent with DEET (25%)

 Case Study-69 year old with aneurysm- recovered but spiked a fever.  Treated with antibiotics, everything.  Ended up to be West Nile Virus she received through transfusion.  

  The problem was 20 yr old female organ donor who had had exposure from 63 different donors- blood right before she died had West Nile.  She passed on disease through organ donation.

 

2002-One out of every 8000 units of blood transfused. was infected with West Nile

- While infectious, screening of blood is not as sensitive as AIDS, Hepatitis

 

 Case Study-5l year old , fever, coughing a lot, respiratory distress- influenza with influenza pneumonia.  Virus infects lining cells of respiratory tract.  The virus that cause influenza-denudes ciliated epithelium. The problem is that in the month of rebuild time, one contracts pneumonia, emphysema.  Most of deaths in elderly.   Cough, Fever, Headache, Myalgia.

 

The tremendous systemic inflammation due to high cytokine mediator release- high inflammatory response.

 

Cold vs. Flu- Never have fever with cold.  Little cough, little myalgia, little inflammation with cold. 

 

Flu treatment- Amantadine, Ramantadine can shorten the duration of illness.  Most of influenza strains today are resistant., but new class call neuraminidase inhibitors- Tamiflu (oral) or Relanza(inhaler) are treatments recommended.   We have a vaccine for influenza.The only contraindication is allergy to eggs.  Research project on vaccine in St. Paul among research that should positive effect of vaccine programs.  Health care workers should be immunized. 

 

Immunization- Vaccine only manufactured in embryonated eggs.  April- choice on strain- mass production- takes six months.  We should change technique, to use recombinant types.

 

Cautions for Cold/Flu 

-        Wash hands, keep hands off nose

-        Do not go to work if sick

-        Cough hygiene

Influenza surface proteins-two Hemagglutinin and Neuroaminadase.

Why are there annual epidemics of Influenza A every winter?  Why can they get infected 2-3 time over 10-20 years – due to antigenic drift.  Virus mutates its structure- 3-4 % of virus- same thing happens with Hepatitis and AIDS.

 

Why are we concerned about global pandemic of the virus?   They are due to an entirely new virus that can spread human to human.  All flu virus start in water birds.  It cannot kill the water bird, but it can kill other birds.  Human influenza- comes from where large populations co-exist with water birds. Recombinant mutation in made. 

 

Three epedimics- 1918 Spanish Flu killed four times as manner soldiers as WWI in France

-        1957- Asian Flu

H3N2 1968- Hong Kong Flu

 

2003-SARS could  have easily been a pandemic.  Credit goes to the efforts of the local countries. Proved power of molecular biology.  The virus was identified in eight days.  WHO coordintated with countries.  246 cases, quarantined, hot line.  Control of Flu requires commitment to work together and help the poor countries.

 

2003-2006   H5N1 Bird Flu- In South Korea outbreak of bird flu spread throughout  SEAsia- slaughtered 150 million birds to try to stop.  Humans were coming down with bird flu.  Median age of victims- 13 years.  Bird flu is a GI disease- kids are playing among the bird poo.  Less than 2% adopted from person to person.  The virus not yet seen in the U.S. This is not a human pandemic- it is a bird influenza. 

 

Why are we not controlling situation like malaria?  Government does not prioritize. Not cost effective in terms of resources. 

 

9/11 woke us up to bioterrorism concerns.  Health and Human Services Web Site  shows how we address bioterrorism.. Vaccines can be developed.  Antivirals can provide treatment. (oseltamivir-Tamiflu).

 

Prparations at UWHC- excercises for isolation/room and ventilation areas. Research- UW Madison is on the forefront of research on H1H1, NSh5n1.  The previous strains have killed multiple times more people. Researchers have reconstrudted strains from exhumed bodies. H5N1 does not spread nasally, but very efficiently with lung.  Patient dies is picture of Septic Shock. 

 

 

We must hang together or assuredly we shall all hang separately- B.Franklin

 

 The lecture was completed at 2:43 p.m. Guest were excused  for the business meeting.

 

 

Business Meeting

 

Dr. Dowsett called the meeting to order. Dr. Abraham reported that 37 members, 8 guests, and one life member attended the meeting.  She stated the minutes of  the last meeting are posted on our web site.  In Dr. Huberty’s absence, Dr. Dowsett reported that the current treasury held $71,000.  In Dr. Ziebert’s absence, Dr. Dowsett reported that plans for the Christmas party were underway, and invitations should be out next week. 

 

Old Business topics included discussion of venue, and projector purchase.  Dr. Dowsett and Dr. Fahey are reviewing our venue options.  Dr. Dowsett reported that Dr. Moser has purchased the digital projector.

 

New Business topic was plaque preparation.  Dr. Abraham will follow up on plaque preparation. 

 

Dr. Lindstrom motioned to adjourn.  The meeting was adjourned at 2:52 p.m.

37 members, 8 guests, 1 life member.