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Emerging Infections Update: 2011
Ruth Lynfield, MD
Minnesota Department of Health
Emerging Infections
• Infectious agents evolve
– Ability to infect new hosts/new populations/new modes of transmission, new geographic/ecological ranges, resistance to therapeutic agents
• Re-emerging infectious diseases
– Recurrence of previously controlled infectious diseases
Case 1
• 10-year-old male from rural Cass County (wooded farm) presented in June with difficulty speaking and swallowing, headache, confusion, and subjective fever for 1 day
– Flaccid symmetrical bulbar paralysis on exam
• 1 week prior had a generalized urticarial rash, followed by a sore throat 2 days later
• 1 week prior to the development of rash parents noted an engorged tick (unknown type) attached to his body
• CSF sample PCR positive for Powassan virus; of the deer tick lineage
Ixodes scapularis
Tick-Borne Disease New to Minnesota, 2008 (cont.)
Western-most case identified in United States
Powassan Virus
• Tick-Borne flavivirus first isolated in 1958 from a case of encephalitis in Powassan, Ontario
• Incubation period usually 1-2 weeks
– Acute onset of muscle weakness and confusion
• Patients (particularly adults) often left with sequelae
• 31 human cases reported in Canada and northeastern United States, 1958-2001
MN Powassan Virus Cases,2008-2011
• 12 cases
• Exposures May – October
• Median age: 56 years (10-70 y); 92% male; 50% previously healthy
• 100% fever, headache; 67% (8) confusion or delirium; 50% (6) rash; 50% (6) muscle weakness
• 58% (7) required ICU care; 1 fatality
• 42% (5) had known persistent symptoms including weakness, dizziness, speech abnormalities, intense fatigue and difficulty concentrating
• 67% (8) had known tick bite; others tick exposed or lived in geographic area where there are ticks
Human Ehrlichiosis due to Novel Ehrlichia: Ehrlichia muris-Like Agent
• 2009-2010: Mayo Medical Lab detected Ehrlichia muris-like agent (EML) in 14 Minnesota and Wisconsin patients
• Patients had illnesses suggestive of anaplasmosis or ehrlichiosis
• EML infection with cross-reactivity to E. chaffeensis could explain some Midwestern cases with positive E. chaffeensis serology
• EML also identified in I. scapularis and Peromyscus mice by PCR
Minnesota 2010 Tick-borne DiseaseDisease
Lyme disease
Human anaplasmosis (HA)
Babesiosis
Human ehrlichiosis (HE)
HA/HE undetermined
HE-EML agent
Powassan disease
Rocky-Mountain spotted fever
No. of Cases
1,293
720**
56**
12**
11
4
3
2**
** Includes confirmed and probable case totals
Reported Tick-Borne Disease Cases,Minnesota, 1986-2010
(n = 14,921)
0
200
400
600
800
1,000
1,200
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
Year of Report
Nu
mb
er o
f R
epo
rted
Cas
es
Lyme disease
Human anaplasmosis
Babesiosis
Minnesota Biomes
Coniferous and mixed
forest
TallgrassAspen
Parkland
Prairiegrassland
Deciduousforest
Minneapolis-St. PaulMetropolitan Area
Distribution of Lyme Disease Cases by County of Residence, MN, 1996-2010
Incidence Rate (cases/100,000 person-years)No Cases >0.0-10.0 >10.0-100.0 >100.0-160.0
2006-20102001-20051996-2000
Timeline of Autochthonous Vector-Borne Diseases of Humans, Minnesota
Malaria
Babesiosis
Anaplasmosis
La Crosse encephalitis
West Nile virus
Lyme disease
18502000
1920
POW
190019601940 1980
2010
Western equine encephalitis
EEE equine outbreak RMSF Fatality
Mosquito-Borne
Tick-Borne
EML
Case 2
Woman in her 50s with a history of depression, had fatigue, insomnia, achy joints, memory loss and confusion x 5 years with worsening of symptoms x 2 years
Case 2 (cont.)
Serological testing
– Indeterminate IFA for Lyme
– Lyme IgM Western blot + (2/3 bands; 2 or more considered positive)
– Lyme IgG Western blot – (3/10 bands; 5 or more considered positive)
Case 2 (cont.)
• Rx with 5 weeks of doxycycline
– Felt better on therapy; worsened off therapy
• Rx cefuroxime and telithromycin x 2-4 months
Case 2 (cont.)
• Developed diarrhea 5 weeks into course
Case 2 (cont.)
• Started on metronidazole
• Developed ascites and severe abdominal pain 2 days later
• Cardiac arrest while undergoing emergency colectomy
• Pseudomembranes found in colon
• Stool positive for C. difficile toxinotype III, binary toxin positive, containing 36-bp tcdC deletion
Case 3
• 7 yo previously well
• Developed headache and abdominal pain, followed one day later by fever
• Evaluated and given IM penicillin for possible strep throat
• Developed seizures next day and admitted to ICU
• CSF: 8,150 WBC/mm3 (90% PMN), 800 RBC/mm3, TP 461 mg/dL, glucose < 20 mg/dL
Wright’s Stain of Cerebrospinal Fluid
Naegleria fowleri
• Thermophilic, free-living ameba
• Fresh water
• Proliferates above 30º C (86º F)
• Can migrate up olfactory nerve to brain
• Primary amebic meningoencephalitis (PAM)
• 111 cases in U.S. 1962–2008
• 1 survived
Naegleria fowleri
• Thermophilic, free-living ameba
• Fresh water
• Proliferates above 30º C (86º F)
• Can migrate up olfactory nerve to brain
• Primary amebic meningoencephalitis (PAM)
• 111 cases in U.S. 1962–2008
• 1 survived
• 2010: cases in AK, TX; 2011: LA, FL, VA
N. fowleri cultured and confirmed by real-time PCR from CSF
3098
7
3098
7
3098
7
3098
8
3098
8
3098
8
3098
9
3098
9
3098
9
Neg
Ctr
1
Neg
Ctr
2
Pos
Ctr
Mar
ker
6 9 12 15 16 21
Illness Onset
Death
Lake A Lake B River
Timeline of Swimming Exposures and Illness
Date
August 2010
7d 5d
Lake A
Typical incubation
Lake A Organic Matter and Algal Bloom
Environmental Testing
• N. fowleri cultured from Lake A water and sediment
• N. fowleri not found at other 2 swimming sites
• N. fowleri from Lake A water and CSF were genotype 3
Precipitation
Maxim
um
Daily T
em
pera
ture
(°
C)
Date – August, 2010
Cen
tim
ete
rs
Ambient Temperature and Precipitation near Lake A, August 1-15, 2010
6
4
2
8
Lake A
≥30° C (86° F) on 6 of 15 days
Maximum Daily Temperature
* Epidemiol. Infect. 2010; 138:968-975
Primary Amebic Meningoencephalitis Cases
MN
Case 4
• 23 month old male with temp to 102oF x 2 days, runny nose and cough x 2 days
• Decreased activity
• No childcare, no travel
• Mother is a nurse in a long-term care facility
• PE significant for mild conjunctival erythema
Case 4 (cont.)
• Small white spots observed on oral mucosa
• Developed vomiting over next day and a rash on face
Measles Epidemiology in the U.S.
• Before introduction of vaccine (1963) approximately 3-4 million cases and 500 deaths annually; 90% prior to age 15 years
• 1989, 2nd dose recommendation
• 1998, ACIP and AAP recommendation of 2 doses for school entry
• Fewer than 150 cases reported each year 1997-2010 in US (37-140/year)
• Globally 164,000 deaths per WHO in 2008
92%
• Dec 1999-July 2000, Dublin
• National immunization rates 79% and < 70% in North Dublin
• 111 children hospitalized
• Pneumonia 47%, tracheitis 32%
• 13 children ICU, 7 ventilated
• 3 deaths
Resurgence of Measles in UK
Resurgence of Measles •
Rise in measles 'very worrying' Friday, 6 February 2009
Measles cases in England and Wales rose by 36% in 2008, figures show. Confirmed cases increased from 990 in 2007 to 1,348 last year - the highest figure since the monitoring scheme was introduced in 1995. Health Protection Agency experts said most of the cases had been in children not fully vaccinated with combined MMR and so could have been prevented. Immunisation expert Dr Mary Ramsay said the rise was "very worrying", adding measles "should not be taken lightly".
More than 600 of the 2008 measles cases occurred in London, where uptake of the vaccine for MMR - measles, mumps and rubella - is particularly low.
Public confidence in the triple MMR vaccine dipped following research - since discredited - which raised the possibility that the jab may be linked to an increased risk of autism. It led to some parents opting to pay privately for single vaccines. Across the UK, 84.5% of two year olds have been immunised with their first dose of MMR.
But by age five, when children are recommended to have a second dose, the latest uptake figures are 77.9%. “ There are still many children out there who were not vaccinated as toddlers over the past decade and remain unprotected ” Dr Mary Ramsay, Health Protection Agency Since 2005, the number of cases of measles has been rising year on year.
There have also been sporadic outbreaks of mumps in recent years.
t
February 2, 2010
Measles outbreaks spread across EuropeCopenhagen, 20 April 2011
Thirty countries in WHO’s European Region have reported a marked increase in measles cases, with 6500 so far in 2011. Epidemiological investigations and genotyping by laboratories confirm exportation of the virus among several countries in the Region and to other regions of the world. Outbreaks and the further spread of measles are likely to continue so long as people remain unimmunized or do not get immunized on time according to the routine
immunization schedule. France faces the largest outbreak, with 4937 measles cases officially reported from January to March 2011, a figure almost equal to the total of 5090 cases reported for whole of 2010.
Measles in France• Outbreak since January 2008• 14,000 cases from January through June 2011
– 6 deaths– 15 neurological complications – 615 severe pneumonia
Surveillance Report July 13,
2011
United States Measles Cases 1985-2010
0
5000
10000
15000
20000
25000
30000
1985
1987
1989
1991
1993
1995
1997
1999
2001
2003
2005
2007
2009
Year
Mea
sles
Cas
es
Minnesota Measles Cases 1988-2010
0
50
100
150
200
250
300
350
400
450
500
1988
1990
1992
1994
1996
1998
2000
2002
2004
2006
2008
2010
Year
Mea
sles
Cas
es
Comparison of 24 Month Old Children Born in Minnesota of Somali Descent and Non-Somali Descent; MMR vs. Varicella
Vaccinations in Hennepin County, Minnesota
0
10
20
30
40
50
60
70
80
90
100
2004 2005 2006 2007 2008 2009
Somali MMR (≥1)
Somali Varicella (≥1)
Non-Somali MMR (≥1)
Non-Somali Varicella (≥1)
Year of Birth
Per
cen
t V
acci
nat
ed
n= 645 Somali,13,565 Non-Somali
n= 685 Somali,11,947 Non-Somali
n= 719 Somali,14,197 Non-Somali
n= 705 Somali,14,509 Non-Somali
n= 739 Somali,14,323 Non-Somali
n= 321 Somali,7,176 Non-Somali
MN Measles Outbreak; February- April 2011
• On March 2, measles confirmed in a 9 month old infant
• Index case 30 month old, US born, returning traveler from Kenya – Rash onset on February 15 (genotype B3)
• 23 confirmed cases
• 19 linked to the 30 month old (20 total)
• age 4 months to 51 years old
• One case in a 34 y.o. who acquired infection in Florida (unknown vaccination status) (genotype D4)
• One case in 27 y.o. who acquired infection in India (vaccinated with 2 doses) (genotype D8)
• One child with unknown exposure, with secondary case (daycare exposure)
Measles Genotypes
Distribution of measles genotypes associated with endemic transmission in various areas of the world based on information available in 2002. JID 2003; 187 (supp 1) Rota and Bellini
Measles Cases
Vaccination status:• Unvaccinated
– 7 cases too young to receive vaccine – 9 were of age but were not vaccinated
• Vaccinated– 1 had received at least 1 MMR– 1 had received 2 MMR– 1 received MMR earlier than recommended age (11 mo)
• 4 unknown vaccine status
14 hospitalizations, no deaths:• 3 pneumonia, 1 croup, 8 otitis media, many with dehydration
Exposure Settings for Outbreak Cases
• Index case acquired infection in Kenya
• Household (4 cases exposed)
• Healthcare (3 cases exposed in E.D.)
• Congregate living for the homeless (8 cases exposed)
• Drop in Daycare (3 cases exposed)
• One unknown exposure with secondary daycare exposure with B3 genotype
Measles Cases August, 2011
• 12 month old returned from Kenya (not Somali)
– Prolonged course in ICU (intubated, measles pneumonia)
• 15 month cousin (brief hospitalization for dehydration, pneumonia)
• 43 yo exposed in waiting room
• 12 and 15 month- no MMR
• 43 yo unknown if vaccinated, but was measles-IgG negative when presented with symptoms
Community health workers immunize children under the age of five against polio and measles, and give them vitamin A and de-worming tablets,
in a house-to-house campaign in the town of Liboi, north-eastern Kenya.
Acknowledgements
• Clinicians, ICPs, and Microbiologists in Minnesota
• Local Public Health
• Epidemiologists, Laboratorians and Student Workers at the
Minnesota Department of Health
• CDC
Questions?