Upload
others
View
2
Download
0
Embed Size (px)
Citation preview
1
BSIM 12th Annual Congres 2007
Emerging and Re-emerging Infectious Diseases
W. PeetermansInternal Medicine – Infectious Diseases
UZ Leuven
Emerging and Re-emerging Infectious Diseases
Clinical syndromes or pathogens never recognised before :HIV, Bartonella henselae, Helicobacter pylori, SARS, etc.
Emerging
Re-emerging
Clinical syndromes or pathogens that are or have been endemic in some parts of the world and come back in a different form or different location :West Nile in USA, severe dengue fever in the Americas, CA-MRSA, Clostridium difficile 027, etc.
Fauci AS. Acad Med 2005;80:1079-1085
King DA et al. Science 2006; 313:1392-1393
2
Emerging and Re-emerging Infectious Diseases
• Dis-Balance between human and microbial species1. Genetic and biologic factors : high replication and mutation rate2. Physical environmental factors3. Ecologic factors4. Social, political or economic factors
• Mostly zoonotic : animal reservoir
• Rapid spread (travel, migration, trade)
• Prepare for deliberately emerging ID : Bioterrorism
Fauci AS. Acad Med 2005;80:1079-1085
King DA et al. Science 2006; 313:1392-1393
Beyond the scope of this presentation
• Aids; Malaria; Tuberculosis including MDR-TB and XDR-TB
• SARS (2003); Ebola (2005)
• New species (Bartonella bacilliformis, NEJM 2007) or
new serotypes (non-vaccine IPD, JAMA 2007) or
new patient populations (aspergillosis in ICU, CID 2007)
• Non-events : Chlamydophila pneumoniae and atherosclerosis (721 hits in pub med, JCM 2005)
3
N. meningitidis infections in Belgium
4
N. meningitidis infections in Belgium
Within the scope of this presentation
• CA-MRSA
• Clostridium difficile 027
• Syphilis and FQ-resistant gonorrhea
• Chikungunya and Dengue fever
• Avian influenza
5
Community-acquired MRSA
• Differs from HC-associated MRSA microbiologicallyand clinically
• Clonal epidemics in children, MSM, prisoners, football players, beauty clinics, etc.
• Nosocomial spread less prevalent but reported
• Still rare in Belgium
Zetola N et al. Lancet Infect Dis 2005;5:275-286
N Engl J Med 2005; 352: 468-475.
6
Community-acquired MRSA : microbiology
• Type IV SCC mec cassette andPanton-Valentine gene for Leucocidin positive
• High producer of multiple toxins
• Susceptible to clindamycin (80%), gentamicin, cotrimoxazole, glycopeptides and linezolid
Zetola N et al. Lancet Infect Dis 2005;5:275-286
Community-acquired MRSA : clinical
• Young healthy people
• Severe skin and soft tissue infections
• Necrotising pneumonia
7
7537SSTI (%)
1576Underlyingdisease (%)
2368Age (yr)
CA-MRSAHC-Associated MRSA
Naimi TS et al. JAMA 2003;290:2976-2984
MRSA in pig and cattle Farmers
• Scc mec cassette type III-IV-V;PVL-negative; non-typable by Sma1 PFGE;new clonal complex ST398 by MLST
Kluytmans J. EID 2007 dec.
• Belgian survey in pig farms44% of pigs were carrier (all ST398)68% of farms had at least 1 carrier pig38% of farmers were carrier
3% in MRSA-free farms50% in MRSA-pos farms
Struelens M. BVIKM 16/11/2007
8
Clostridium difficile
Clostridium difficile associated diarrhea : Classical
• Mild to moderate disease : diarrhea and pseudomembranous colitis
• Well-known risk factors
• Metronidazole first-choice (VRE threat)
• High recurrence rate (20%) associated with poorantibody response
Bartlett JG. Ann Intern Med 2006;145:758-764
Aslam S et al. Lancet Infect Dis 2005;5:549-557
9
Clostridium difficile associated diarrhea : New
• Incidence increased 4-fold
• Severe disease : toxic megacolon; septic shock; perforation or bleeding; death (15%)
• Refractory to metronidazole; oral vancomycin superior
• (frail) elderly
• Very high recurrence rate (>50%)
→ New epidemic strain : PCR ribotype 027, PFGE-NAP1Bartlett JG. Ann Intern Med 2006;145:758-764
Pepin J et al. Clin Infect Dis 2005;40:1591-1597
Zar FA et al. Clin Infect Dis 2007;45:302-307
Clostridium difficile NAP1 – Ribotype 027
• Resistant to fluoroquinoles : independent risk factor
• Hyperproducer of toxin A and toxin B (toxinotype III)
• Deletion of tcdC in pathogenicity locus
• Producer of a binary toxin
• Clonal spread
Bartlett JG. Ann Intern Med 2006;145:758-764
Mc Donald LC et al. N Eng J Med 2005;353:2433-2441
Loo VG et al. N Engl J Med 2005;353:2442-2449
Warny M et al. Lancet 2005;366:1079-1084
10
Clostridium difficile associated disease : Treatment
• Discontinue implicated antibiotic
• Hydration and electrolyte replacement
• Avoid antiperistaltics
• oral vancomycin 4 x 125-250 mg daily for 10 days
• Initiate infection control measures
• Surgical consultation if severe CDAD
• Retreat if recurrence
Bartlett JG. Ann Intern Med 2006;145:758-764
Kuijper EJ et al. Curr Op Infect Dis 2007;20:376-383
Clostridium difficile associated disease : Prevention
• Restrictive use of antibiotics
• Early identification of new cases (toxin EIA)
• Isolation precautions and cleaning (spores!)
• Probiotics if recurrence (?)
• Prolonged vancomycin treatment if recurrence
• IVIG if multiple recurrences
• (experimental : active and passive immunisation)
Bartlett JG. Ann Intern Med 2006;145:758-764
Kuijper EJ et al. Curr Op Infect Dis 2007;20:376-383
11
STD:
syphilisgonorrhoea
LGV
Syphilis
12
Re-emergence of Syphilis
• 156 new registered cases in Flanders (jan - july 2007)
• Ongoing outbreaks, mainly MSM (50% HIV-pos.)
• Clinical diagnosis and serology
• Standard treatment: benzathine–Pen G (availability?)
Sasse A et al. Euro Surveillance 2004;9:6-8
Peterman TA et al. Curr Op Infect Dis 2007;20:54-59
0
5
10
15
20
25
30
35
Period 1 Period 2 Period 3 ¨Period 4 Period 5
Num
ber o
f syp
hilis
dia
gnos
es
MSMHetero MWomen
I P H - 2005
Syphilis cases per sex and sexual orientation, Sentinel Network of Clinicians, Belgium, Oct.-Jan. periods, 2000 - 2005
13
Primary syphilis
Secundary syphilis
14
Gonorrhoea
Gonorrhoea
• 4-fold increase over 10 years (MSM; sextravel)
• Transport medium or bed-side inoculation
• PPNG (>20%) and doxycycline resistance (>40%)
• Increasing resistance to fluoroquinolones→ 28% (2002-2003) → 47% (2004-2005)
• First-choice treatment :
ceftriaxone 250 mg IM or spectinomycin 2g IM
• Also treat for NGU
15
Lymphogranuloma Venereum
• Chlamydia trachomatis LGV serovars L1-3
• Endemic in tropics – outbreaks in MSM
• Necrotising lymphadenitis – deep anorectal ulcers
• Clinical diagnosis and PCR (serology)
• Doxycycline 200 mg for weeks
Fever in returned travelers
16
Fever in returned travelers
• Spectrum of diseases according to travel destination and time of presentation
• Tropical diseases (39%) and cosmopolitan infections (34%)
71%58%21%Pretravel advice
8%18%42%Hospitalisation
9%24%45%Malaria
18%29%52%Fever
TouristTraveler VFRImmigrant VFR
Bottieau E et al. Arch Intern Med 2006;166:1642-1648
Freedman DO et al. NEJM 2006;354:119-130
Leder K. et al. Clin Infect Dis 2006;43:1185-1193
Chikungunya
• Arbovirus transmitted by Aedes mosquitoes
• Endemic in Africa, South- and South-East Asia
• Outbreaks: India 2006-2007 and Réunion 2005-2007
260000 cases in 775000 population
• Acute febrile syndrome with rash and incapacitatingarthralgia
• Severe disease : MODS – encephalitis – death
• PCR (Pasteur, Paris) and serology
• Symptomatic treatment
Pialoux G et al. Lancet Infect Dis 2007;7:319-327
Seneviratne SL et al. J Travel Med 2007;14:320-325
17
Chikungunya and Dengue
Dengue
• Arbovirus (4 sterotypes) transmitted by Aedesmosquitoes
• Asia, Latin-America, Subsaharan Africa
• 2 clinical syndromes (WHO)• Classic Dengue Fever• Dengue Haemorrhagic Fever and Dengue Shock Syndrome :
capillary leakage
• Rapid Ag-test and serology
• Symptomatic treatment
Halstead SB. Lancet 2007;370:1644-1652
18
Dengue : Geographical Distribution
Avian Influenza
19
Influenza : The Pandemic Threat
• Influenza A and B winter epidemicsHA and NA mutations : Ag drift
• Influenza A pandemicsHA and NA reassortment : Ag shift
• Stable lineage• No immunity in population• Human to human transmission• Pathogenicity virulence in humans
Origin of antigenic shift and pandemic influenza
Lancet 2003; 362: 1733-1745.
20
The Influenza Pandemics of the 20th century
• 1918-19: Spanish flu (H1N1; swine or water fowl)20-50 million deaths worldwide (500.000 in USA)nearly half of deaths were young healthy adults
• 1957-58: Asian flu (H2N2; re-assortment with avian type)70.000 deaths in USA
• 1968-69: Hong-Kong flu (H3N2; re-assortment with avian type)34.000 deaths in USA
• 1977-78: Russian flu-swine flu(H1N1; similar to virus that circulated up to 1950’s)low death rate
H5N1 Avian Influenza
• Ongoing spread since 2004 (clade 1 – clade 2)
• Human cases due to direct exposion to poultry
• (extremely) high death rate
• Resistant to adamantanes (clade 1) and sporadic resistance to oseltamivir reported
21
NEJM 2006;355:2174-2177.
22
Cumulative number of confirmed cases of Avian Influenza A / H5N1 (WHO 25-07-2007)
192319Total
154
3812
EgyptTurkey
1725Thailand4295Vietnam81102Indonesia
DeathsCasesCountry
23
H5N1 Influenza : Virulence• Pro inflammatory cytokine responses induced by influenza A H5N1
viruses in primary alveolar and brocheal epithelial cellsChan MCW et al. Respir Res 2005;6:135
• Fatal outcome of human H5N1 influenza A is associated with high viral load and hypercytokinemia
de Jong MD et al. Nature Med 2006;12:1203-1207
• Inhibition of the cytokine response does not protect against lethal H5N1 influenza infection
Salomon et al. PNAS 2007;104:12479-12481
• A single mutation in the PB1-F2 of H5N1 and 1918 influenza A viruses contributes to increased virulence
Conenello GM et al. PLoS pathogens 2007;3:e141
• Aberrant immune response in lethal infection of macaques with the 1918 influenza virus
Kobasa D et al. Natrure 2007;445:319-323
Pandemic Preparedness Plan
• Surveillance and virological research
• Pandemic vaccine(s) development
• Risk management1. Contain impact on morbidity and mortality
– Vaccination– Antiviral drugs– Reduction of transmission
2. Sustain good management of cases
3. Contain impact on social disruption
24
Emerging and Re-emerging Infectious Diseases
• Don’t forget the lesson of the sixties“… anticipate that within some measurable time allmajor infections will have disappeared”“Close the book on Infectious Diseases”
US Surgeon General 1968
• Invest in– Knowledge of broad range of I.D.– Surveillance systems to detect new evolutions– Research in new modalities of diagnosis, treatment
and prevention
25
R. KochNobelprice 1905
R. Warren en B. MarshalNobelprice 2005
Emerging and Re-emergingInfectious Diseases