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2/7/2020
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Infectious Diseases in Clinical Practice February 20, 2020
Bryn A Boslett, MDAssistant Clinical ProfessorUniversity of California, San Francisco
Emerging (and re‐emerging) pathogens
Disclosures
• I have no financial disclosures
• I will not discuss off‐label uses of medications or unapproved laboratory tests
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Content and Learning Objectives
• Define the factors that influence the development and spread of new human pathogens
• Discuss examples of pathogens that have recently emerged or re‐emerged
• Describe surveillance and control strategies for emerging human pathogens
What are emerging or re‐emerging infections?• Emerging infectious disease (EID) describes a new organism appearing as a pathogen in humans…
• New species (HIV)
• Known organism previously unrecognized as pathogen (H pylori)
• Or, a previously known pathogen that is occurring with increased frequency, severity or global distribution
• Altered form of known pathogen (MRSA)
• Altered geographic spread (West Nile Virus)
Nature 451, 990–993 (2008) doi:10.1038/nature06536
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http://www.bu.edu/articles/2016/neidl‐symposium‐infectious‐diseases/
Factors that influence the emergence of new pathogens• Change in human behavior / society – migration, travel, sanitation, decline in vaccination
• Change in climate / ecosystem – warming, floods, droughts, earthquake, human development
• Change in the microorganisms – selective pressure of antibiotics, bioterrorism, human‐animal interaction leading to recombination events
According to the World Health Organization, 60% of the agents recognized as human pathogens come from the
animal kingdom (zoonoses)
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Travel
• ~1 billion travelers cross international boarders annually
• 60 million travel from the US – half to developing countries – most often for leisure
• Adventure travel is becoming more popular
• In one study, only 15% have a travel medicine visit
• Of patients in travel clinic, 30% with <2 weeks lead time
Duval, et al. J Travel Med 2003; 10:4–10.Hamer DH, et al. Mayo Clin Proc Innov Qual Outcomes. 2017 Apr 28;1(1):78‐90.
Where we travel
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https://www.cdc.gov/climateandhealth/effects
Climate change
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Vector‐borne diseases
US Reportable Vector‐borne Diseases
#Reported cases (2013)
Tick‐borne 36,307
Lyme disease 36,307
Spotted fever Rickettsia 3,359
Anaplasma/Ehrlichia 4,551
Babesia 1,792
Tularemia 203
Mosquito‐borne
West Nile Virus 2,469
Malaria 1,594
Dengue 843
Eastern equine encephalitis
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Flea‐borne
Plague 4
https://health2016.globalchange.gov/vectorborne‐diseases
Change in Microorganisms –acquisition of resistance genes
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COMBAT study – travelers acquire resistance genes at alarming rates
Arcilla MS, et al. Lancet Infect Dis. Vol 17, Issue 1, Pages 78‐85 (January 2017)
Percentages of travelers acquiring β‐lactamase‐producing Enterobacteriaceae, by sub‐region
Case Studies in Emerging Infections
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Influenza virus
• Epidemics infect 15‐20% of world’s population annually
• 250 – 500,000 deaths/year
• Pandemics have occurred sporadically throughout history
• 1918‐19: “Spanish flu”; H1N1 virus
• 1957‐58: “Asian flu”; H2N2 virus
• 1968‐69: “Hong Kong flu” H3N2 virus
• 2009‐10: pH1N1 virus
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• Three influenza types:• Influenza A – humans, mammals, birds• Influenza B – humans only• Influenza C – humans only
• Many influenza A subtypes:• Differentiated by HA and NA • 18 HA subtypes, 11 NA subtypes• Named by specific combination (eg, H1N1,
H3N2, etc)
Influenza Pathogenesis
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• Hemagglutinin (HA)
• Binds sialic (neuraminic) acid receptors viral entry
• Agglutinates RBCs
• Neuraminidase (NA)
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Viral Structure
• Segmented Genome
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• Hemagglutinin (HA)
• Binds sialic (neuraminic) acid receptors viral entry
• Neuraminidase (NA)
• Cleaves sialic acid to release virus
Viral Structure
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• Antigenic Drift• Minor mutations in HA or NA• Influenza A, B, C
• Antigenic Shift• Complete change of HA, NA or both• Only occurs in Influenza A(requires non‐human intermediate) SHIFT
Neuraminidase Hemagglutinin
DRIFT
Antigenic Changes
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Antigenic Shift
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Antigenic Shift
• March 2013: H7N9 virus first detected in humans
• Poultry‐human transmission, limited human‐to‐human transmission
• 6 epidemics in China to date, last in 2016‐2017, total of ~1600 cases
• 40% mortality rate across epidemics
Avian influenza H7N9
https://www.cdc.gov/flu/avianflu/h7n9-virus.htm. Updated Dec 2018.
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• 1997: H5N1 humans (Hong Kong)
• 2004‐2005: Epidemics in poultry, some human cases
• Today: Highly Pathogenic Avian Influenza (HPAI H5N1)
• >800 people infected via human‐human transmission
• 50 countries, considered endemic in Bangladesh, China, Egypt, India, Indonesia, and Vietnam
• No US cases to date, 1 case in Canada• 60% mortality
Highly Pathogenic Avian Influenza H5N1
CDC, Highly Pathogenic Avian Influenza A (H5N1), Updated Dec 12. 2018
Coronavirus
• Large family of viruses
• Widely circulating among humans and animals including cats, camels and bats
• In humans, usually gives “common cold”
• Animal coronavirus can evolve, spread to humans in close proximity, presumably via respiratory droplets, details unknown
• This has resulted in several large‐scale global outbreaks
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SARS‐CoV
• 2002: Severe Acute Respiratory Syndrome emerged in Guangdong, China
• Bats civet cats humans, then spread between humans
• 29 countries, >8000 cases, >800 deaths
• SARS has reappeared four times – three laboratory accidents, and once in southern China where the source of infection remains undetermined
• No widespread transmission since 2004
• 2012: Middle East Respiratory Syndrome (MERS Co‐V)
• All cases linked to Arabian peninsula
• Outbreaks from returning travelers South Korea in May 2015
• 186 infected, 36 deaths
• Mortality rate 30‐40%
MERS Co‐V
CDC, Middle East Respiratory Syndrome (MERS). Updated Dec 8, 2015.
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2019 Novel coronavirus
• 2019‐nCoV: first identified in Wuhan, China in Dec 2019
• SARS‐like illness – fever, cough, pneumonia
• Initial cases reported exposure to seafood market, which was closed
• Later cases did not have contact, confirming human‐human spread
• Wide range of presentations – from mild respiratory illness to respiratory failure
2019‐nCoV Map (Jan 22)
• Virus sequence released by China on 1/10
• First exported case (Thailand) on 1/13
• First US case on 1/21
• >500 cases reported by China on 1/22
World Health Organization, as of Jan. 22, 2020.
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Situation in the US (so far)
• Jan 8: CDC issues clinician alert for patients with pneumonia symptoms and returning from China
• Jan 17: US airport screening begins – SFO, JFK, LAX. Soon added ATL and ORD.
• Jan 21: First US case reported in returning traveler to Seattle. CDC activates Emergency Response System
Procedures and guidance at airports
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CDC Patient Under Investigation (PUI) criteria
https://www.cdc.gov/coronavirus/2019‐nCoV/clinical‐criteria.html
Specimen Collect and Hold for PCR at CDC• CDC and/or local DPH will advise yes/no to testing
• If yes, CDC issues patient tracking #
• Healthcare team collects:• Upper respiratory (OP and NP swab; wash/aspirate)
• Lower respiratory (sputum, BAL, tracheal aspirate)
• Serum
• Urine and stool (?)
• Local public health labs will collect and ship to CDC next business day. CDC can arrange weekend courier.
https://www.cdc.gov/coronavirus/2019‐nCoV/guidelines‐clinical‐specimens.html
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Infection Control Guidance
• Standard, Contact, Airborne precautions PLUS eye protection
• Gown, gloves, N95, goggles or face shield
• Surgical mask on patient
• Negative pressure room if possible
• What if a facility without negative pressure room?• Avoid that scenario if possible
• Evaluate patient at end of day, outside, etc.
• Take room out of use for 2 hours
• If patient mildly ill, home isolation is an option
https://www.cdc.gov/coronavirus/2019‐nCoV/infection‐control.html
Good Info Sources
• CDC https://www.cdc.gov/coronavirus/2019‐nCoV/summary.html
• CIDRAP http://www.cidrap.umn.edu/
• StatNews https://www.statnews.com/category/health/
• FluTrackers (reports not vetted) https://flutrackers.com/forum/forum/‐2019‐ncov‐new‐coronavirus
• New York Times https://www.nytimes.com/section/health
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Zika virus
• Mosquito‐borne RNA flavivirus: • like Japanese encephalitis, dengue, West Nile, and yellow fever viruses
• Named after the Zika forest in Uganda where the virus was first isolated in a rhesus monkey
• Prior to 2007, only sporadic infections in Africa and SE Asia
• Aedes species mosquitoes• Live in and around households
• Aggressive daytime biters
• Sexual and IVDU transmission also possible
Cao‐Lormeau VW, Emerg Infect Dis, 2014
Zika disease characteristics
• Incubation period: 2‐4 days (range 1‐14)
• Clinical manifestations: 1 in 5 infected may have fever, rash, joint pain, conjunctivitis
• Severe complications (rare): Guillain Barre
• Risk of fetal complications greatest concern• 250 maternal cases in US in 2016
• Fetal microcephaly in 10‐15% of cases
• Highest risk in 1st trimester
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Differentiating from similar mosquito‐borne viruses
Zika map
https://wwwnc.cdc.gov/travel/files/zika‐areas‐of‐risk.pdf
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Imported Zika in the United States, 2015‐2016
US States: 819 travel‐associated cases (6/30/16)‐ 11 sexually transmitted, 48+ pregnant, 4 GBS
CDC recommendations
For pregnant women:
• Avoid travel to Zika high‐risk areas
• Testing after travel to risk area only if symptomatic
• If male partner traveled, avoid sex for duration of pregnancy
Considering pregnancy:
• Avoid for 2 months if woman visited
• Avoid for at least 3 months if male partner visited
https://www.cdc.gov/pregnancy/zika/testing‐follow‐up/exposure‐testing‐risks.html
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What’s new in 2020?
• No current local transmission of Zika virus in the continental United States, including Florida and Texas (last case in 2017)
• Travel restrictions have been lifted on many countries, as there are no active outbreaks
• Still need to check updated maps prior to planning travel –
https://wwwnc.cdc.gov/travel/page/zika‐information
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Ebola virus
• RNA filovirus zoonosis • Fruit bats as likely reservoir
• Five distinct subtypes, similar clinical syndromes
• First isolated in DR Congo and South Sudan in 1976
• 1976 – 2013: sporadic outbreaks, most in central Africa, ~1600 deaths
• 2013 – 2016 : largest outbreak to date, Western Africa, ~29,000 cases and 11,323 deaths
https://www.who.int/en/news‐room/fact‐sheets/detail/ebola‐virus‐disease. Accessed Jan 14, 2020
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Ebola disease characteristics
• Transmitted via direct contact with infected body fluids
• Blood, urine, vomit, diarrhea, semen, vaginal secretions, saliva, sweat, breast milk
• Bushmeat handling
• Incubation period 2 – 21 days • Initial symptoms of fever, fatigue, muscle pain, headache, sore throat
• Later: vomiting, diarrhea, rash, impaired kidney and liver function, spontaneous bleeding internally and externally
• Case fatality rate: 25 – 90%
Ebola map2013 outbreak
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Current Ebola outbreak
Ebola future directions
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Measles
• Aerosolized RNA paramyxovirus • Airborne virions from cough, sneeze can linger for 2 hours
• Contact with contaminated surfaces
• Attack rate of 90%
• First described in 9th century Persia
• 1976 – 2013: sporadic outbreaks, most in central Africa, ~1600 deaths
• 2013 – 2016 : largest outbreak to date, Western Africa, ~29,000 cases and 11,323 deaths
Measles characteristics
• Incubation 10‐12 days
• Prodrome 2‐4 days (contagious)• High fever, often >40 C• Cough, Coryza, Conjunctivitis• Koplik spots pathognomonic
• Rash (still contagious for first ~4 days)• Papular, face torso extremities• Fades in same order, over 5‐6 days
• Complications• Common: pneumonia (largest cause of death), otitis media, diarrhea
• Rare: subacute sclerosing panencephalitis (0.1%)
https://www.aafp.org/afp/2017/0601/p729.htmlAmerican Journal of Neuroradiology May 2004, 25 (5) 892‐894.
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Subacute sclerosing panencephalitis (SSPE)
• Progressive neurological disorder caused by slow, but persistent, measles viral infection in the CNS
• Initially: Personality change, fevers, headaches
• Then: Jerking movement, spasticity, seizures, vision loss, dementia
• Finally: Writhing, rigidity, coma and death
• Occurs between 1 in 1000 and 1 in 10,000 cases of measles, nearly always fatal within 3 years
• Onset typically 6 – 8 years after measles infection (range 1 ‐ 27 yrs)
• Risk highest in males, children who develop measles at age < 2yo
• No known cure, treatments all experimental
Measles Global Vaccination Rates, 1980 – 2010
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1963
US Measles Cases, 2010‐2019
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2019: 31 states with measles cases
Medical exemptions
BB1
What about outside of the US?
Slide 55
BB1 Bryn Boslett, 1/17/2020
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MMR recommendations for adults• Considered immune:
• Documented measles IgG positive
• Have an official record of 2 MMR vaccinations
• Born prior to 1957 likely have natural immunity
• May need MMR:• Adults vaccinated 1963 – 1967: may have received inactivated vaccine.
• Adults vaccinated 1967 – 1989: may have received only one dose MMR.
• Whom to target: international travelers, healthcare workers, college students, local to outbreak
Surveillance and Control of Emerging Infections
Needed to detect and respond to emerging infections:
• A functional and effective surveillance and response system (including isolation rooms, ventilation control, soap and clean water, and adequate personal protective equipment [PPE])
• A skilled public health workforce
• A functional and networked laboratory
• Effective coordination and intersectoral collaboration
WHO estimates that >70% of the world remains underprepared to prevent, detect, and respond to a public
health emergencies
WHO International Health Regulations (2005)
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Global Health Security Agenda (GHSA)• Launched in Feb 2014, a US‐lead collaboration to strengthen the world’s ability to prevent, detect, and respond to infectious disease threats
• 67 partner countries to date, 11 action packages developed
One Health concept
• Problem: Human diseases and animal diseases have been considered as separate entities
• Most emerging diseases are vector‐borne or zoonoses
• Doctors, veterinarians, ecologists rarely work together
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One Health initiative
• 2007: One Health formed interdisciplinary movement to create collaborations between animal, human, and environmental health organizations
• American Veterinary Medical Association
• American Medical Association
• Centers for Disease Control and Prevention
• United States Department of Agriculture
• Since 2017, the WHO and EU have adopted and been promoting One Health strategy
Examples of One Health in action
• Stepwise Approach to Rabies Elimination (SARE) Workshop in Beijing in 2019
• FARMER app in Thailand – crowdsourcing to report abnormal illnesses and deaths in humans and animals
• Influenza and zoonoses education campaign among youth in US agriculture
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Summary
• Many factors have changed interactions between people, animals, and our environment
• More than half of all known human infections have their root in animals and insect vectors
• Vaccines are powerful tools, when available and properly utilized
• Collaboration is needed across boarders and disciplines to focus limited resources on preventing, detecting, and responding to diseases of greatest global concern