Download EMERGING … and RE-EMERGING INFECTIOUS DISEASES

EMERGING … and RE-EMERGING
INFECTIOUS DISEASES
LARRY M. BUSH, MD, FACP
Affiliated Professor of Biomedical Sciences
Charles E. Schmidt College of Medicine
Florida Atlantic University
Affiliated Associate Professor of Medicine
University of Miami-Miller School of Medicine
http://www.who.int/mediacentre/factsheets/fs310/en/
http://www.who.int/mediacentre/factsheets/fs310/en/
Definition

Emerging infectious disease
Newly identified & previously unknown
infectious agents that cause public health
problems either locally or internationally
Definition

Re-emerging infectious disease
Infectious agents that have been known for some
time, had fallen to such low levels that they were
no longer considered public health problems &
are now showing upward trends in incidence or
prevalence worldwide
NEWLY IDENTIFIED INFECTIOUS
DISEASES AND PATHOGENS
Year
Disease or Pathogen
1993
Hantavirus pulmonary syndrome (Sin Nombre
virus)
Vibrio cholerae O139
Guanarito virus
Hepatitis C
Hepatitis E; human herpesvirus 6
HIV
Escherichia coli O157:H7; Lyme borreliosis;
human T-lymphotropic virus type 2
Human T-lymphotropic virus
1992
1991
1989
1988
1983
1982
1980
Source: Workshop presentation by David Heymann, World Health Organization, 1999
NEWLY IDENTIFIED INFECTIOUS
DISEASES AND PATHOGENS
Year
Disease or Pathogen
2012
2009
2004
2003
1999
1997
1996
MERS-CoV
H1N1
Avian influenza (human cases)
SARS
Nipah virus
H5N1 (avian influenza A virus)
New variant Creutzfelt-Jacob disease;
Australian bat lyssavirus
Human herpesvirus 8 (Kaposi’s sarcoma virus)
Savia virus; Hendra virus
1995
1994
Source: Workshop presentation by David Heymann, World Health Organization, 1999
GLOBAL EXAMPLES OF EMERGING AND
RE-EMERGING INFECTIOUS DISEASES
AS Fauci
FACTORS CONTRIBUTING TO
EMERGENCE OR RE-EMERGENCE
OF INFECTIOUS DISEASES
• Economic development and changes in the use of
land, including deforestation, reforestation, and
urbanization
• Global warming - climate changes cause changes
in geographical distribution of agents and vectors
• Changing human behaviours, such as increased
use of child-care facilities, sexual and drug use
behaviours, and patterns of outdoor recreation
• Social inequality
FACTORS CONTRIBUTING TO
EMERGENCE OR RE-EMERGENCE
OF INFECTIOUS DISEASES
• International travel and commerce that
quickly transport people and goods vast
distances
• Changes in food processing and
handling, including foods prepared from
many different individual animals and
countries, and transported great distances
FACTORS CONTRIBUTING TO
EMERGENCE OR RE-EMERGENCE
OF INFECTIOUS DISEASES
• Evolution of pathogenic infectious agents by
which they may infect new hosts, produce
toxins, or adapt by responding to changes in the
host immunity.(e.g. influenza, HIV)
• Development of resistance by infectious
agents such as Mycobacterium tuberculosis and
Neisseria gonorrhoeae to chemoprophylactic or
chemotherapeutic medicines.
FACTORS CONTRIBUTING TO
EMERGENCE OR RE-EMERGENCE
OF INFECTIOUS DISEASES
• Resistance of the vectors of vector-borne
infectious diseases to pesticides.
• Immunosuppression of persons due to
medical treatments or new diseases that result
in infectious diseases caused by agents not
usually pathogenic in healthy hosts (e.g.
leukemia patients)
FACTORS CONTRIBUTING TO
EMERGENCE OR RE-EMERGENCE
OF INFECTIOUS DISEASES
• Deterioration in surveillance systems for
infectious diseases, including laboratory
support, to detect new or emerging disease
problems at an early stage (e.g. Indonesian
resistance to “scientific colonialism”)
• Illiteracy limits knowledge and implementation
of prevention strategies
• Lack of political will – corruption, other
priorities
FACTORS CONTRIBUTING TO
EMERGENCE OR RE-EMERGENCE
OF INFECTIOUS DISEASES
• Biowarfare/bioterrorism: An unfortunate
potential source of new or emerging disease
threats (e.g. anthrax and letters)
• War, civil unrest – creates refugees, food and
housing shortages, increased density of living,
etc.
• Famine causing reduced immune capacity, etc.
• Manufacturing strategies; e.g., pooling of
plasma, etc.
The global air network
Million of Passenger (Mil)
Average annual number of global airline
passengers by decade, 1950-2010
IATA 2010
Decade
Commercial Air Traffic Over a 24 Hour Period
What did these Epidemic Infectious
Diseases have in Common?
• All were caused by zoonotic pathogens
• All spread by modern transportation
• Most had Asian origin
• Laboratory and clinical diagnoses were problematic
• Poor communication among countries
• Major economic impact
Live Animal Importation into the USA - 2002
• 47,000 mammals
 28 species of rodents
• 379,000 birds
• 2 million reptiles
& Poisonous snakes
• 49 million amphibians
• 223 million fish
Data from U.S. Fish & Wildlife Service
Exotic Mosquito Species Recently
Introduced and Established in the US
•
•
•
•
•
Aedes (Stegomyia) albopictus
Ochlerotatus (Aedes Finlaya) togoi
Ochlerotatus (Aedes Finlaya)
japonicus
Aedes bahamensis
Culex biscayensis
EBOLA VIRUS
Mysterious Disease
Books – ‘Hot Zone’ and ‘Outbreak’
Comes…. and then Goes
“A” list of Bioterrorism Agents (Hemorrhagic Viral Fever)
Ebolavirus; family Filovirus
5 species (Bundibugyo, Tai Forest, Reston, Sudan, and
Zaire {90% fatlality})
Fruit Bats likely reservoir
1976 1st outbreaks : Sudan and Zaire
(Democratic Republic of the Congo)
Central Africa, remote villages, rainforests
Feb 2014 Guinea ; 1st this far west : largest to date
26
FAMILY DISEASE (VIRUS) NATURAL DIST
SOURCE
Arenaviridae
Lassa Fever
Africa
Rodent
Bunyavurudae
Rift Valley Fever
Africa
Mosquito
Flaviviridae
Yellow fever / Dengue
Africa, S. America Mosquito
Filoviridae
Marburg / Ebola
Africa
Fruit Bat
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1976- 2 outbreaks EBOLA Hemorrhagic Fever
Northern ZAIRE (Democratic Republic of Congo) and SUDAN
5 Species EVD: Zaire, Sudan, Tai Forest, Bundibugyo, Reston
ZOONOTIC Infection: BATS most likely reservoir
28
1976-2012: 33 Outbreaks
Year
Country
Cases
Death
1976
Zaire
318
88%
1976
Sudan
284
53%
1999
Zaire (DRC)
315
81%
2001
Uganda
415
53%
2002
Rep Congo
143
89%
2007
Uganda
149
25%
2007
Dem Rep Congo
264
71%
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EVD Cases and Deaths*
Reporting Date
Total Cases
(Suspected,
Probable, and
Confirmed)
Confirmed Cases
Total Deaths
Guinea
3 Mar 15
3,237
2,833
2,141
Liberia
1 Mar 15
9,249
3,150
4,117
Sierra Leone
3 Mar 15
11,497
8,383
3,565
United Kingdom**
29 Dec 14
1
1
0
Nigeria**
15 Oct 14
20
19
8
Spain**
27 Oct 14
1
1
0
Senegal**
15 Oct 14
1
1
0
United States**
24 Oct 14
4
4
1
Mali**
23 Nov 14
8
7
6
23,406
14,142
9,457
TOTAL
Updated case counts available at http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/case-counts.html.
* Total cases include probable, suspected, and confirmed cases. Reported by WHO using data from ministries of health
**There are currently no cases of EVD in Senegal, Nigeria, Spain, the United States, the United Kingdom, and Mali.
30
Outbreak Distribution — West Africa,
March 4, 2015
Map includes total confirmed EVD cases reported to WHO
31
EVD Cases (United States)
•
EVD has been diagnosed in the United States in four people: one (the
index patient) who traveled to Dallas, Texas from Liberia, two healthcare
workers who cared for the index patient, and one medical aid worker who
traveled to New York City from Guinea
– Index patient – Symptoms developed on September 24, 2014 approximately
four days after arrival, sought medical care at Texas Health Presbyterian
Hospital of Dallas on September 26, was admitted to hospital on September
28, testing confirmed EVD on September 30, patient died October 8.
– TX Healthcare Worker, Case 2 – Cared for index patient, was self-monitoring
and presented to hospital reporting low-grade fever, diagnosed with EVD on
October 10, recovered and released from NIH Clinical Center October 24.
– TX Healthcare Worker, Case 3 – Cared for index patient, was self-monitoring
and reported low-grade fever, diagnosed with EVD on October 15, recovered
and released from Emory University Hospital in Atlanta October 28.
– NY Medical Aid Worker, Case 4 – Worked with Ebola patients in Guinea, was
self-monitoring and reported fever, diagnosed with EVD on October 24,
recovered and released from Bellevue Hospital in New York November 11.
Information on U.S. EVD cases available at http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/united-states-imported-case.html.
32
EVD Cases (United States)
• During this outbreak, five health workers and
one journalist have been infected with Ebola
virus while in West Africa and transported to
hospitals in the United States. Five of these
patients have recovered.
– One of the health workers died on November 17
after being transported from Sierra Leone to
Nebraska Medical Center.
33
EBOLA CONTACT TRACING, DALLAS, TEXAS
CONFIRMED CASES: 3
CONTACTS (recognized exposure to Ebola patient’s fluids or surface)
Current: 0
Completed Surveillance: 11
Total: 11
POSSIBLE CONTACTS (possible exposure to same)
Current: 53
Completed Surveillance: 113
Total: 166
TOTALS
Current: 53
Completed Surveillance: 124
Total: 177
………..AND ONE PET DOG CONFIRMED NEGATIVE !!
34
Human-to-Human Transmission
• Infected persons are not contagious until
onset of symptoms
• Infectiousness of body fluids (e.g., viral load)
increases as patient becomes more ill
– Remains from deceased infected persons are
highly infectious
• Human-to-human transmission of Ebola virus
via inhalation (aerosols) has not been
demonstrated
35
Ebola Virus Transmission
• Virus present in high quantity in blood, body fluids, and
excreta of symptomatic EVD-infected patients
• Opportunities for human-to-human transmission
– Direct contact (through broken skin or unprotected mucous
membranes) with an EVD-infected patient’s blood or body fluids
– Sharps injury (with EVD-contaminated needle or other sharp)
– Direct contact with the corpse of a person who died of EVD
– Indirect contact with an EVD-infected patient’s blood or body fluids
via a contaminated object (soiled linens or used utensils)
• Ebola can also be transmitted via contact with blood, fluids,
or meat of an infected animal
– Limited evidence that dogs become infected with Ebola virus
– No reports of dogs or cats becoming sick with or transmitting Ebola
36
Detection of Ebola Virus in Different
Human Body Fluids over Time
37
Ebola Virus Pathogenesis
• Direct infection of tissues
• Immune dysregulation
• Hypovolemia and vascular collapse
– Electrolyte abnormalities
– Multi-organ failure, septic shock
• Disseminated intravascular coagulation (DIC)
and coagulopathy
Lancet. Mar 5, 2011; 377(9768): 849–862.
38
Early Clinical Presentation
• Acute onset; typically 8–10 days after exposure
(range 2–21 days)
• Signs and symptoms
– Initial: Fever, chills, myalgias, malaise, anorexia
– After 5 days: GI symptoms, such as nausea, vomiting, watery
diarrhea, abdominal pain
– Other: Headache, conjunctivitis, hiccups, rash, chest pain, shortness
of breath, confusion, seizures
– Hemorrhagic symptoms in 18% of cases
• Other possible infectious causes of symptoms
– Malaria, typhoid fever, meningococcemia, Lassa fever and other
bacterial infections (e.g., pneumonia) – all very common in Africa
39
Clinical Features
• Nonspecific early symptoms progress to:
– Hypovolemic shock and multi-organ failure
– Hemorrhagic disease
– Death
• Non-fatal cases typically improve 6–11 days after symptoms
onset
• Fatal disease associated with more severe early symptoms
– Fatality rates of 70% have been historically reported in rural Africa
– Intensive care, especially early intravenous and electrolyte
management, may increase the survival rate
40
Examples of Hemorrhagic Signs
Hematemesis
Gingival bleeding
Bleeding at IV Site
41
Laboratory Findings
• Thrombocytopenia (50,000–100,000/mL range)
• Leukopenia followed by neutrophilia
• Transaminase elevation: elevation serum aspartate
amino-transferase (AST) > alanine transferase
(ALT)
• Electrolyte abnormalities from fluid shifts
• Coagulation: PT and PTT prolonged
• Renal: proteinuria, increased creatinine
42
EVD: Expected Diagnostic
Test Results Over Time
Critical information: Date of onset of fever/symptoms
IgM
IgG
viremia
0
3
10
days post onset of symptoms
Fever
RT-PCR
ELISA IgM
ELISA IgG
IgM: up to 3 – 6 months
IgG: 3 – 5 years or more (life-long persistance?)
43
EBOLA TREATMENT
• No FDA-approved vaccine or medicine (e.g., antiviral drug) is
available for Ebola.
• Symptoms of Ebola are treated as they appear. The following basic
interventions, when used early, can significantly improve the
chances of survival:
– Providing intravenous fluids (IV) and balancing electrolytes
(body salts)
– Maintaining oxygen status and blood pressure
– Treating other infections if they occur
• Experimental vaccines and treatments for Ebola are under
development, but they have not yet been fully tested for safety or
effectiveness.
44
Zmaap®: (Leaf Biopharmaceutical, San Diego, CA)
monoclonal antibodies humanized by genetic engineering
BRINCIDOFOVIR: (Chimerix)
Prodrug of Cidofovir; Activity vs CMV, Adenovirus, Samllpox, Ebola Virus
TKM-Ebola® (Tekmira Pharm, Vancouver, Canada)
Combination of small interfering RNAs target 3 of the 7 proteins in Ebola Virus
45
Patient Recovery
• Case fatality rate between 53-64% among hospitalized
patients in Guinea, Liberia, and Sierra Leone in the 2014
Ebola outbreak
– Case fatality rate is likely much lower with access to intensive care
• Patients who survive often have signs of clinical
improvement by the second week of illness
– Associated with the development of virus-specific antibodies
– Antibody with neutralizing activity against Ebola persists greater than
12 years after infection
• Prolonged convalescence
– Includes arthralgia, myalgia, abdominal pain, extreme fatigue, and
anorexia; many symptoms resolve by 21 months
– Significant arthralgia and myalgia may persist for >21 months
– Skin sloughing and hair loss has also been reported
References: 1WHO Ebola Response Team. NEJM 2014; 2Feldman H & Geisbert TW. Lancet 2011; 3Ksiazek TG et al. JID
1999; 4Sanchez A et al. J Virol 2004; 5Sobarzo A et al. NEJM 2013; and 6Rowe AK et al. JID 1999.
46
DO ALL SERO-POSITIVE PERSONS FALL ILL ???
One post Ebola outbreak, 71% of SEROPOSITIVE individuals did NOT have
disease
Another study showed that 46% of ASYMPTOMATIC CLOSE CONTACTS with
ACTIVE EBOLA patients had turned SEROPOSITIVE
AYSMPTOMATIC SEROPOSITIVE people DO NOT spread disease but
contribute to HERD IMMUNITY and thereby dampen epidemic spread of disease
Lancet, Oct 25, 2014
47
EBOLA PREVENTION
• Epidemiologic history
• Recognizing clinical symptoms
• Strict isolation measures and PPE (personal
protective equipment) use
• Airport screening
• ?? Travel restriction from epidemic countries
48
SARS: The First Emerging Infectious
Disease Of The 21st Century
No infectious disease has spread so fast and far as SARS did in 2003
SARS Cases
19 February to 5 July 2003
Total: 8,439 cases, 812 deaths,
30 countries in 7-8 months
Europe:
10 countries (38)
Canada (243)
Russian Fed. (1)
Mongolia (9)
China (5326)
USA (72)
Kuwait (1)
India (3)
Colombia (1)
Hong Kong (1755)
Korea Rep. (3)
Macao (1)
Taiwan (698)
Malaysia (5)
Viet Nam (63)
Singapore (206)
Brazil (3)
Indonesia (2)
Philippines (14)
Thailand (9)
South Africa (1)
(
Australia (5)
New Zealand (1)
Source: www.who.int.csr/sars
MERS CoV
Caused by a CORONAVIRUS (so was SARS)
1st human cases reported in September 2012
All cases linked to countries in or near Arabian Peninsula
Can spread by close contact : 20% HCW
Approx. 973 cases : 30% - 40% Mortality
Median age 49 yr old; 65% male
Many with Comorbidities
Incubation 5 days (range 2-15 days)
Symptoms : Fever, Headache, Dyspnea and Dry Cough
Diarrhea, Sore Throat
Laboratory : Leukopenia, Lymphopenia, Thrombocytopenia
Elevated LDH, CXR (various patterns)
Testing :
ELISA, PCR, Naso-Oropharyngeal, Serum
Treatment : Supportive
Isolation : Airborne, PPE
52
MERS CoV RESERVOIRS
53
MERS - Epidemiology
54
MERS - Epidemiology
55
MERS – Transmission and Diagnosis
• Spreads from ill people to others through
close contact (e.g., caring for or living with an
infected person)
– Nosocomial spread reported
– Sustained community spread not observed
• Camels have been implicated as a reservoir
and possible direct source for MERS-CoV in
humans
• Diagnosis – PCR & Serology
56
MERS – United States
• May 2014 – two unlinked imported cases of
MERS
– Indiana
– Florida
• Both cases among healthcare providers who
lived and worked in Saudi Arabia
• Active MERS-CoV infection has not been
found in any contact of either U.S. MERS
patient
57
MERS – Symptoms and
Complications
• Severe acute respiratory illness:
–
–
–
–
Fever
Cough
Shortness of breath
Some have gastrointestinal symptoms (N, V, D)
• Most of the people who died had an underlying
medical condition (DM, cancer, chronic lung, heart,
and kidney disease, immune disorders)
• Some patients had mild or no symptoms
• Average incubation 5-6 days (range 2-14 days)
58
MERS – Prevention & Treatment
• No vaccine (yet)
• Usual preventive methods:
–
–
–
–
–
–
Wash hands
Cover nose/mouth with a tissue when coughing or sneezing
Avoid touching eyes, nose, mouth with unwashed hands
Avoid close contact with sick people
Clean and disinfect frequently touched surfaces
Healthcare personnel should adhere to recommended infection
control measures, including standard, contact, and airborne
precautions, when managing symptomatic close contacts, patients
under investigation, and patients who have probable or confirmed
MERS-CoV
• No specific antiviral treatment – only supportive care
59
MOST FATAL EVENT
IN HUMAN HISTORY
WORLDWIDE FATALITIES:
50-100 MILLION
US FATALITIES:
675,000
70
65
Age
60
55
50
45
40
35
1900 1906 1912 1918 1924 1930 1936 1942 1948 1954 1960
Date
U.S. LIFE EXPECTANCY AT BIRTH
61
U. S. Army training camp
and other military outbreaks
were deadly but well studied
medically/epidemiologically
62
INDOOR CHURCH SERVICES WERE
BANNED BY HEALTH DEPARTMENTS
63
64
65
EXTENSIVE PUBLIC
HEALTH EXPERIENCE
WITH TB CONTROL
HEAVILY INFLUENCED
INFLUENZA
PREVENTION
EFFORTS IN THE U. S.
66
Influenza’s Gonna Do What
Influenza Does: Change!
Influenza A
 H1 - H17
 N1 – N10
Aquatic birds
Poultry
Cats
Humans
Pigs
Horses
Aquatic
mammals
Dogs
WISCONSIN STATE LABORATORY OF HYGIENE - UNIVERSITY OF WISCONSIN
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The Changeability of Influenza
Antigenic Shift
www.flu.gov
Antigenic Shift
When a new
subtype (a novel
HA and/or NA) of
influenza A
emerges in the
host (humans)
WISCONSIN STATE LABORATORY OF HYGIENE - UNIVERSITY OF WISCONSIN
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Timeline of Emergent and Pandemic
Influenza Viruses in Humans
Swine H3
Swine H1
Avian H9
Avian H7
Avian H5
Type A
2009 H1pdm A
H1
H3
H2
H1
1999
1918
1940
1957 1968 1977
1997
2011
2003
2009
2013
B/Yam
Type B
B/Vic
WISCONSIN STATE LABORATORY OF HYGIENE - UNIVERSITY OF WISCONSIN
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Influenza Immunization Rates:a
Well Below Healthy People 2010 Goals1,2
100
Goal: 90% for 65 years
of age and older
Percent of Patients Vaccinated
90
80
70
With Age Indication
Goal: 60% for 18-64
years of age
60
Health-care
Personnel
With High-risk Condition
50
Pregnant
Women
Household
Contacts of
People at
High Risk
18-44
5-17 18-49
Without High-risk
Condition
40
30
20
10
0
6-23 50-64 >65
mo
5-17 18-49 50-64 18-64
5-17 18-49 50-64
All
Age (years)
a
All rates are for 2007-2008 influenza season, except 6-23 months of age and health-care personnel (2006-2007).
References: 1. CDC. MMWR. 2009;58(RR-8):1-52. 2. Poland GA, et al. Am J Med. 2008;121(suppl 2):S3-S10.
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It’s NOT all about influenza….
other diseases of public health
importance…..
WISCONSIN STATE LABORATORY OF HYGIENE - UNIVERSITY OF WISCONSIN
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Enterovirus D68
Background








Enteroviruses are very common respiratory
viruses (10-15M/year).
Transmission respiratory route (person-toperson)
Cause a wide variety of illnesses.
Types that circulate are variable &
unpredictable.
>100 EV types
Peak activity during summer and fall.
There are no vaccines or antiviral therapeutics.
Children with asthma are more vulnerable.
WISCONSIN STATE LABORATORY OF HYGIENE - UNIVERSITY OF WISCONSIN
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MOSQUITO …borne diseases
CHIKUNGUNYA VIRUS INFECTION
Togaviridae family; genus Alfavirus
Transmitted by mosquito Aedes aegypti
(also albopictus)
Bantu language “that which BENDS up”
1st outbreak 1952 Tanzania
Historically Africa, S/SE Asia, Italy, France
Now >4000 cases in Caribbean
>15 cases in South Florida
86
Aedes albopictus & Aedes aegypti:
Worldwide Distribution
Aedes albopictus
Aedes aegypti
88
CHIKUNGUNYA CLINICAL SYNDROME
Sudden HIGH Fever
Headache, Myalgias, Rash (50%)
Polyarthralgias-arthritis
wrists, ankles, and knuckles
Prolonged Prostration
Second Fever course
Joint pains can persist a long time
Serologic Diagnosis
No Vaccine
Symptomatic Treatment
Rarely life-threatening
Often confused with Dengue Fever
93
Measles
• Measles = Rubeola (caused by a morbillivirus)
• Highly contagious viral respiratory illness
– Approximately 9 out of 10 susceptible persons with close contact to a
measles patient will develop measles
– Droplet or airborne (2 hours) spread (use N-95 masks)
– Prodrome of fever (up to 105oF), malaise, and the three “C”s –
cough, coryza and conjunctivitis – and a pathognomonic enanthem
(Koplik spots)
– Prodrome is followed by a maculopapular rash about 14 (7 to 21)
days after exposure, spreading from head to trunk to the lower
extremities
– Contagious from 4 days before to 4 days after rash
• Diagnosis: serology (IgM) and/or molecular testing (oral or
nasopharyngeal swab)
111
Measles
• Before introduction of the vaccine in 1963 (and MMR in
1971), an estimated 3-4 million people were infected
annually:
–
–
–
–
400-500 people died
48,000 were hospitalized
4,000 developed encephalitis, with 1,000 developing chronic disability
Subacute sclerosing panencehalitis – rare fatal degenerative CNS
disease generally developing 7-10 years after measles infection
• Highest risk for severe illness or complications: < 5 or > 20
years old (especially > 60 years old); immunocompromised;
pregnant women; malnourished; vitamin A deficiency
• Very effective vaccine (93% protected after one injection;
97% after two)
112
Measles
• In 1998, MMR safety was questioned:
– British researcher Andrew Wakefield, along with 12 co-authors,
published a paper in the Lancet claiming evidence of measles virus in
the digestive systems of autistic children. In press conferences after
the paper was published, Wakefield suggested a relationship
between the MMR (measles, mumps and rubella) vaccine and
autism. Wakefield then recommended that the combination MMR
vaccine be suspended in favor of single-disease vaccinations given
separately over time. Vaccination rates in England dropped in
response, from more than 90% to 80% or lower—well below the level
required for herd immunity to measles. Measles cases, meanwhile,
began to rise: while only 56 cases were confirmed in Wales and
England in 1998, 1,348 were confirmed by 2008.
114
Measles
• By 2004, additional information was uncovered:
– It was reported that some of the subjects of Wakefield’s paper had
been recruited by a lawyer involved in a lawsuit against vaccine
manufacturers; in response to this and other problems with the paper,
10 of the 12 co-authors eventually retracted the interpretation
regarding a link between the vaccine and autism. Numerous
epidemiological studies performed since have also provided
additional evidence that no such link exists. In 2010, Britain’s
General Medical Council ruled that Wakefield had engaged in
misconduct during the course of conducting and publishing the study.
Subsequently, the Lancet formally retracted the paper; in May 2010,
Wakefield was banned from practicing medicine in Britain.
– Despite this and the lack of any evidence to support a link between
vaccines and autism, some groups remain convinced of the
allegations raised by Wakefield in 1998.
115
Measles
•
•
Majority of people who got measles were unvaccinated
Measles was deemed eradicated in the United States in 2000
– No endemic cases since that time
– All cases imported (brought in to the United States by unvaccinated travelers
(Americans or foreign visitors) who get measles while they are in other
countries
•
•
•
Since 2000, at most ~200 (usually < 100) cases occur annually in the
United States
In 2014 there were 644 cases from 27 states
In 2015 there were 173 cases already from 17 states
– Majority of cases (73%) in 2015 are part of a multi-state outbreak originating
in California linked to visiting the Disneyland Resort
– Outbreak likely started with a traveler infected with a strain acquired in
Philippines based on molecular analysis
117
Measles
118
Measles
119
Measles
• Evidence of immunity:
– Written documentation of adequate vaccination:
• one or more doses of a measles-containing vaccine administered on or
after the first birthday for preschool-age children and adults not at high
risk
• two doses of measles-containing vaccine for school-age children and
adults at high risk, including college students, healthcare personnel, and
international travelers
– Laboratory evidence of immunity
– Laboratory confirmation of measles
– Birth before 1957
• MMR Coverage in Michigan (19-36 months, 2013): 89.2%
– Pockets with much lower rates of vaccination
120
Antibiotics Revolutionized Medicine
• Enable complicated surgery
• Enable cancer chemotherapy
• Enable critical care medicine
• Enable care for premature babies
• Enable organ transplantation
• Changed medicine from a diagnostic
profession to a treatment profession
Antimicrobial Resistance
130
Antibiotic Resistance Threats
September 2013
131
Antibiotic Resistance Threats
132
Newer Antimicrobials
2010 - Present
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•
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October 29, 2010: Ceftaroline (Teflaro) – Forest Laboratories – treatment of
bacterial skin infections and bacterial pneumonia
May 27, 2011: Fidaxomiccin (Dificid) – Optimer Pharmaceuticals – treatment of
Clostridium difficile diarrhea
December 28, 2012: Bedaquiline (Sirturo) – Johnson & Johnson – treatment of
multi-drug resistant tuberculosis
June 20, 2014: Tedizolid (Sivextro) – Cubist Pharmaceuticals – Treatment of
acute bacterial skin and skin structure infections
May 23, 2014: Dalbavancin (Dalvance) – Durata Therapeutics – Treatment of
acute bacterial skin and skin structure infections
August 6, 2014: Oritavancin (Orbactive) – The Medicines Company – Treatment
of acute bacterial skin and skin structure infections
December 19, 2014: Ceftolozane-azobactam (Zerbaxa) – Cubist – Treatment of
complicated UTIs and complicated intra-abdominal infections
February 26, 2015: Ceftazidime-avibactam (Avycaz) – Actavis – Treatment of
complicated UTIs and complicated intra-abdominal infections
Good start, but…
136
Microbial Threats to Health