Infectious Diseases

Anca Streinu-Cercel MD PhD

May 2019
• Infectious diseases remain a leading cause of
morbidity and mortality worldwide, with HIV,
tuberculosis and malaria estimated to cause
10% of all deaths each year.

• New pathogens continue to emerge, as

demonstrated by the SARS epidemic in 2003
and the swine flu pandemic in 2009, EBOLA in
2014, MERS-COV 2013 on gooing, E coli
hemolytic-uremic syndrome….
CDC Travel Notice Definitions

http://wwwnc.cdc.gov/travel/notices, accessed ian 2016

 Themes:
• Environment
• Pathogen agent
• Host
• Interaction microbes-host
• Infectious
• Contamination
• Defenses mechanism
3 milliards of years of microbial species development passed before
animal and plants appear on Earth
 We live in a BACTERIAL World
• 3 milliards of years of microbial species development passed before
animal and plants appear on Earth

• Microbes represents 60% of earth biomass

• We estimate that < 0.5 % of the

2-3 milliards of bacterial species
have been identified

• But only o small part of the existing

• microbes are pathogens for the humans
A.S. Fauci CID, 2001

Cellular composition of the human body:

• 1013 eukaryotic cells
• 1014 microbiene cells
• Represents endogen flora
• 500 commensal bacterial species colonies GI tract
Bonnie Bassler: How bacteria "talk"
Bonnie Bassler: How bacteria "talk"
Bonnie Bassler: How bacteria "talk"
Bonnie Bassler: How bacteria "talk"
Bonnie Bassler: How bacteria "talk"
Bonnie Bassler: How bacteria "talk"
Human body, animals, water, food, soil… active state or dormant

Prions
 Where are this micro organisms that
causes infections coming?
• Microorganisms that produce infections (sporadic,
epidemic, endemic)
– Endogenous: commensal\saprophyte
– Exogenous: air, soil, water, food, animals,
humans, vectors

• By the origin/place of infectious :

– Community acquired infectious
– Health care associated infections
– Hospital acquired infectious- nosocomial
 ID importance
• 2 out of 10 causes of death are due to ID1:
– Pneumonia and flu
– Sepsis
• ID represents an important cause of death2:
– Elderly
– Imunodeficient
– Chronic diseases
– Imunosupresive treatments

1: Minimo AM et al: Deaths: final data for 2004. Natl Vital Rep Stat 55:1, 2007
2: Lopey et al: Global nad regional burden of diseases and risk factors, 2001: systematic analysis of
population health data. Lancet 367:1747,2006
 Infectious new clasification:
Community acquired Nosocomial
infectious infectious

Community acquiredHealth care associated Nosocomial

infectious infections infectious

2009 definition change

 Infectious classification
Community acquired infectious Nosocomial infectious

Community acquired infectious Health care Nosocomial infectious

associated
infections

G-neg MDR:
Germs AB susceptable +
non-fermentativi:
G-neg posibil
-piocianic
MDR ± ESBL
MDR-multi drug resistant -acinetobacter
ESBL-extended spectrum beta lactamases
Are all microorganisms
causing diseases?

Which microbes are causing and

where are they coming from?
Saprophyte: μorganism that growth
without determining pathological signs Pathogen: μorganism
( symbioses) capable to produce ID
Opportunists: infectious agent that
becomes pathogen when the immunity
is altered
 Other sources?
• Germs transmission:
• Human to human ……
Indirect Direct:
• Fomites (clothes, blankets, door • Droplet
handles etc) • Aerosol
• Vectors (e.g. mosquitoes) • Skin to skin
• Food and water
• Intermediate hosts (e.g. snails)
What makes a microorganism
“dangerous”?
 BIOLOGIC CHARACTERISTICS OF
INFECTIOUS AGENTS

• Infectivity – the ability to infect a host

• Pathogenicity – the ability to cause disease in

the host

• Virulence – the ability to cause severe disease

in the host

• Immmunogenicity –the ability to induce an

immune response in the host
 Infectious Disease Terms

• Infectious dose –number of organisms needed to successfully infect

• Latent period -exposure to infectiousness interval
• Incubation period – interval from exposure to clinical symptoms
• Infectious period – interval during which host can transmit infection
• Reproductive rate – ability of an agent to spread in populations
• Virulence
• Pathogenicity
• Immunogenicity
• Outbreak – limited spread
• Endemic – usually present; steady prevalence
• Epidemic – rapid spread
• Pandemic – occurring across countries and in multiple populations
 Important Terms Used for
Infectious Diseases (1 of 2)
 Important Terms Used for
Infectious Diseases (2 of 2)
 Colonized or Infected:
What is the Difference?
• Colonization: bacteria is present without evidence of
infection (e.g. fever, increased white blood cell count)
• Infection: active process where the bacteria is causing
damage to cells or tissue;

• If an infection develops, it is usually from bacteria that

colonize patients, e.g. their endogenous microbial flora, but
can also exogenous source, e.g. transmitted by hands of
HCW
Infection:
 Time spam to manifest the bacterial infection
Time Diseases Microorganism Mechanism

Minutes Food borne disease Clostridium perfringens Preform Toxin

Hours Necrotizing fasciitis Streptococcus pyogeness Bacterial spred

Days Antrax Bacillus anthracis Resistence to
macrofage ingestion
Weeks Pulmonar Abces Oral Anaerobs Proces of piogenic
necrosis
Month Bacterial Endocardites β hemolitic Streptococcus Cardiac involvment-
special location
Years Osteomielites S.aureus Piogenic infectious of
(persistent) an osteal tissue +/-
implanted devices
Years TB Mycobacterium Reactivate of latent
(latentt) tuberculosis site
Decade Oncogenes Helicobacter pylori Persistent inflamation
plus select cellular
abnormalities
 HOST defences mecanisms

VIRULENCE AGENT PATOGEN HOST DEFENSIS MECANISMS

HOST defences mecanisms

/Adaptive Immunity
 Innate defense mechanism

Anatomical Barriers:
Skin and mucosa- mechanic chemical and biological
protection
Aponevroze, seroase
biological protection chimical mechanical,
Macrophages
Dendritic cells
Natural killer (NK)cells
 Inflammatory reaction
(vasodil + aflux de cel sang şi fact umorali)
stimulare monocite\macrophage cu sinteză IL1

Centrii termoreglăriifebră
Măduva hematogenă neutrofilie
Stimulează neutrofile fagocitoza
LB creşte producţia de Ac
LT sinteza de IL2
Fibroblast proliferate fibre de collagen
Ficat sinteza proteinelor de fază acută
 Host Non specific response

Phagocitosis
2 types of cells macrophages and neutrophils
stages:
•Chimiotaxis = activates cells to the site of infection(C3a, C5a +
complex C5b, 6,7)
•Opsonize = recognition + Training of pathogen agent for
phagocytosis by docking with IgG, C3b)
need to opsonize: pneumococ, stafilococ auriu
H.influenzae, piocianic, Klebsiella,
do not need to opsonize: BGN, staphylococci alb
•Ingestion = fagozom forming
•Digestion =docking with lysosome + inactivate & intracellular
destruction of the pathogen agent; after destruction PN are destroy
puss, MN are not destroy
 Host Non specific response
• Complement
– Protein Complex (C1-9) cascade activation
– Activate C lytic complex C6-C9
• Classical pathway: Ag-Ab bound
• Alternative pathway: non specific, endotoxin (BGN), polizaharid
bacterian (BGP), aggregate by Ig
• Lectin activation pathway: mannose binding lectin->binds
bacterium -> C3b->..
– Activated complement cascade: produces membrane attack
complexes MAC
• Punch holes in the surface of foreign organisms->complex C6-
C9 (Neisseria, BGN)
• Opsonisation invaders by C3b ++phagocytosis
• proinflamator effect <- C3a & C5a
• Modulate LB proliferation
• Increases the activity cytotoxic Ac dependent cells NK
Specific response
Liza celulelor infectate de către
celule T citotoxice
Formare de Ac de către limfocitele B
în cadrul RI umoral T dependent
 Host specific response (1)

Humoral Immunity
Globulin (gamaglobuline) recognition and specific react with
Ag
• Produce by Limfocite B; 5 class Ig: M,G, A, D, E
• Duties :
– Antitoxic
– Bactericidal (by C activate – Neisseria, BGN)
– Cellular mediated cytotoxicity, Ab dependent (Ab
recognize Ag from infected cells and bind by NK cell Fc,
producing the infected cell death)
– Opsonis for extracellular multiplying bacteria
– Local defense (IgA): inhibitates bacterial
adherence+neutralisis viruses\toxins
– Neutralizes some extracellular viruses (vermicelli,
rubella)
 Host specific response (2)
Cellular Immunity (important for inf due to intracellular growth
microorganisms, mediate by Limfocite T)
• Lymphocyte T
– LT helper (CD4) - amplify RIU\RIC by stimulating the proliferation
LB\LT - limfokinelor
– LT suppressor (CD8) – decreases RIU\RIC
• Citokine-limfokine
– Glycoprotein that permit cooperate\interaction between immunity
cells
• Interferon
– glicoproteine species specific
– Biological activity :
• antiviral
• imunomodulator
• anti-tumoral
– 3 tips:
• alfa IF: produced by monocite
• beta-IF: produced by fibroblaste umane
• gama-IF: produced by LT sensibilizate (LTH1)
Microbial attack  celular & humeral mechanism

pro-inflammatory Cytokines anti-inflammatory Cytokine

TNFα
IL1, IL8 IL4
IL6 IL10
IFNγ - IL1ra
IL6

Local & general scaring, fibrosis

Inflammation
 Antibacterial Immunity
 NESPECIFIC defence: opsonizare / fagocitoza = rol primordial for extracelular
Bacteria
 SPECIFIC HUMORAL defence : Bacteria that induce Ab sintesis:
toxigene bacteria (tetanos, difterie)
Extracelular bacteria
Rol of Ab antibacterien:
antitoxic = protect (botulism / tetanos / difterie)
neutralisis bacterial enzime (stafilococ, streptococ)
opsonisis = favor fagocitoza of extracelular bacteria(pneumococ, H.iinfluenza,
piocianic, Klebsiella, stafilococ auriu)
Nespecific bacterianal lisis (by activarea C5-9): H.influenza, Neisserii,
Enterobacterii
local imunity: IgA secretorii (împiedică aderarea la mucoase)
 SPECIFIC CELULAR defence : intracelular bacteria
which multiplie / persist în macrofage away from Ab
vulnerabilty the action LT citotoxice\NK
Produce late hypersensitivity reaction (granuloame cronice TBC etc)
 Antiviral Immunity
Virusis = multiply stricty intracelular = celular imunity (rol
primordial)

 CELULAR IMUNITY : citotoxic events celular mediated-distroy

infected cell
2 mecanisme citotoxice:
Citotoxicitate antiviral specific
 LT citotoxice CD8+
 Ag specific , no need for Ac specific
 ag viral e prezentat LTc de o celulă care posedă Ag CMH cls I
Citotoxicitate celular Ab dependent
 cells NK
 nespecific Ag
 cel NK recunosc / lisis infected cell only in the presentsof NK Ab fix

 HUMORAL IMUNITY : virusurile sensibile la AV numai în timpul viremiilor

 Antifungal Immunity

 NESPECIFIC DEFENCE
 skin / mucosa = barrier mecanic & fizico-chimică
 fagocitosis:
neutrofile / macrofage
important rol in inf : Candida, Aspergillus,
Criptococcus, Histoplasma
neutrophil abnormalitis patients -> SFI
 CELULAR IMUNITY : most important!
 Antiparasits imunitatea
Protozoar
majority infections chronic evolution
Imun response does not permit complete parasite elimination
• Celular Imunity :
Esential for : T. gondii / Leishmania
citotoxicity Ab-dependent: most important mechanism
By eozinofil, presence IgE
Patients with impeard ID celulară (HIV) : frequent inf and
severe with protozoare
• Humoral Imunity: rol modest = Ab low protective rol
 Metazoare: important rol celular imunity
 Imune deficites
• Humoral Imunity
– Hipo/agamaglobulinemia congenital (infecţii cu bacterii cu multiplicare
extracelulară)
– Deficit de IgA (infecţii respiratorii/digestive repetate)
• Complement impearment (infecţii cu bacterii cu multiplicare
extracelulară, Neisseria C6-9)
• Splenectomia (pneumococ H.influenzae, meningococcal)
• Neutropenia
• Functional granulocite abnormalitis (granulomatoza cronică
familială, deficit de G6PDH)
• LT deficit (infecţii cu germeni cu dezvoltare intracelulară)
– Congenital: sd Di George
– Dobândit: hemopatii maligne, transplante, trat imunosupresoare,
denutriţie, malnutriţie, infecţie HIV
• Other imune deficite :
– Diabetis (afectează chemotactismul, fagocitoza, bactericidia PN)
– Hepatic Chirosis, etilism (pneumococ, infectarea spontană a lichidului
de ascită)
 NEWLY IDENTIFIED INFECTIOUS DISEASES AND
PATHOGENS (1)
Year Disease or Pathogen
1993 Hantavirus pulmonary syndrome (Sin Nombre
virus)
1992 Vibrio cholerae O139
1991 Guanarito virus
1989 Hepatitis C
1988 Hepatitis E; human herpesvirus 6
1983 HIV
1982 Escherichia coli O157:H7; Lyme borreliosis;
human T-lymphotropic virus type 2
1980 Human T-lymphotropic virus
Source: Workshop presentation by David Heymann, World Health Organization, 1999
 NEWLY IDENTIFIED INFECTIOUS DISEASES AND
PATHOGENS (2)
Year Disease or Pathogen
2012 MERS-CoV
2009 H1N1
2004 Avian influenza (human cases)
2003 SARS
1999 Nipah virus
1997 H5N1 (avian influenza A virus)
1996 New variant Creutzfelt-Jacob disease;
Australian bat lyssavirus
1995 Human herpesvirus 8 (Kaposi’s sarcoma virus)
1994 Savia virus; Hendra virus

Source: Workshop presentation by David Heymann, World Health Organization, 1999

Take home message