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

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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?