NATURAL HISTORY OF THE GENUS VIBRIO INFECTION CHOLERA

NATURAL HISTORY OF THE
    GENUS VIBRIO INFECTION

                  CHOLERA
    An Etiological and Epidemiological
     Approach, Clinical Consequences

 Prof. Dr. Ludovic Păun, Prof. Dr.Emanoil Ceauşu,
                Conf. Dan Duiculescu
„Dr.V.Babeş” Clinic for Infectious and Tropical Diseases
            „Carol Davila” UMP, Bucharest

• Cholera, an acute diarrhea disease which induced
  dehydration, developed in human communities,
  including at a worldwide: endemic, epidemic and
  pandemic.
• Until thwas considered to be transmitted exclusively
  among humanse end of the 70s, cholera, by a
  digestive transmission pathway, by infected
  individuals or infected asymptomatic individuals.
• The epidemic and pandemic evolution,
  consequences of the V. Cholera contaminated food
  and water ingestion, the ‘’digestive pathway’’ is the
  conceptual constant of the epidemiology and clinical
  description of cholera

Distribution of the countries which reported cholera
                              cases to WHO in 2008

• Importated cases of cholerae
 Mortality rate

V Cholerae infection is classified as a
           group B biological weappon
• We consider (a personal and assumed
  opinion) that unprotected scientific progress
  will not delay in becoming useful for those
  involved in bioterrorism*

• *Bioterrorism - unique and particular variety of terrorism, that deals
  with the relationship between two living beings: the etiological agents
  of biological weapons (unicellular microorganisms) and/or the toxins
  that they produce and the multicellular living macroorganisms such as
  humans, animals, plants etc.

•   Bioterrorism as a part of terrorism from a social, political, economical
    and ideological point of view, includes specifically acute infectious
    diseases, naturally or deliberately transmissied.

Results from recent research
• The results of recent research support
  the singular, unitary, dynamic character,
  constituent of the natural history basis
  of the Genus Vibrio.

Concept and Trends in Transmissible
Infectious Diseases from 21s Century
   The Global Infectious Threat and
    Implications for the United States
               John C. Gannon,
     Chairman, National Intelligence Council
           NIE 99-17D, January 2000

 This report represents an important initiative on
 the part of Intelligence Community to consider
 the national security dimension of a
 nontraditional threat. It responds to a growing
 concern by senior US leaders about the
 implications- in terms of health, economics and
 national security- of the global infectious diseases
 threat.

Globalization of the Infectious
                Diseases
• It has determined the World Health Organization (WHO)
  to elaborate a new version of the International Sanitary
  Regulations (ISR WHO 2005).

• Addendum no. 2 of ISR defines the procedures for the
  confirmation of those infectious diseases suspicions that
  have the potential to spread nationally or internationally
  and the procedures to follow until the start of the
  pandemic evolution and during it

• In Weekly epidemiological record, 31st July 2009, no. 31,
  pg 309-324 (editorial note) it is recommended to
  integrate the concept and surveillance measures of
  the pandemic evolution of cholera, included in the ISR

CHOLERA AND OTHER VIBRIO INFECTIONS*),**)
     Diversification of the infectious diseases
          produced by the Vibrio genus

Diarrhea syndrome
Infection of soft tissues
Primary septicemia
Cholera gravis: severe clinical form of cholera - “Double
     etiology” – serogroups 01; 0139

•    *) Harrison′s Principals of Internal Medicine -17th edition
     2008.
•    **)From a morphological point of view all vibrio species have
     similar characteristics as well as etiological specificity for the
     clinical features that they induce.

ECOLOGY OF THE ETIOLOGICAL AGENT OF
                  CHOLERA - V.CHOLERAE

• V.Cholerae is a component of the microbial ecosystem of estuaries,
  rivers, tidal-rivers and marine coastlines.
• Together with plankton species (live plankton crustaceum
  copepod!), part of the zooplankton and the aquatic fauna in rivers,
  gulfs and estuaries they open the ocean as a hostess of the Vibrio
  genus.
• V.Cholerae was found on the shell and inside the bowls of copepods
  (10³ – 105); it is an essential vector for this human pathogen and
  dissemination.
• The numerical multiplication of the copepods and of chitin covered
  species of the zooplankton for which V.Cholerae is a “commensally
  or symbiotic” germ induce the numerical growth of it in the aquatic
  environment and are a prognostic factor of the development of
  endemic cholera.
• Bangladesh experience (filtering drinking - water by very simple
  means):
   – has significantly reduced the amount of cases of clinical
      cholera.

ENVIROMENTAL IMLICATIONS ON THE
BIOLOGICAL DYNAMICS OF THE VIBRIO GENUS

• Scientific research with international collaboration
  has been conducted in Calcutta, India and Modlib
  – Bangladesh, which included satellite surveillance
  looking at:
   – Surface and deep water temperature.
   – Rate of precipitation.
   – Chlorophyll concentration.
   – Salinity (saturation degree of salty water)
   – Others
• Conclusion: “the role of climatic changes in
  the natural evolution of V.Cholerae has been
  confirmed”

Perspective
    Using Satellite Images of Environmental
     Changes to Predict Infectious Disease
                    Outbreaks

• Timothy E. Ford, Rita R. Colwell, Joan B. Rose,
  Stephen S. Morse, David J. Rogers, and Terry L.
  Yates1
•   Author affiliations: University of New England, Biddeford, Maine, USA (T.E.
    Ford); University of Maryland, College Park, Maryland, USA (R.R. Colwell);
    Johns Hopkins University Bloomberg School of Public Health, Baltimore,
    Maryland, USA (R.R. Colwell); Michigan State University, East Lansing,
    Michigan, USA (J.B. Rose); Columbia University Mailman School of Public
    Health, New York, New York, USA (S.S. Morse); Oxford University, Oxford,
    UK (D.J. Rogers); and University of New Mexico, Albuquerque, New Mexico,
    USA (T.L. Yates)

Infection cycle with V. Cholerae (schematic
                description)

                                    Epithelial
                                      cells

                           Microvillus adherence          Epithelial
              Epithelial
                               Colonization                 cells
                 cells

           Adherence to and                        Colonization and
       penetration of the mucous                   spreading (ileum)
            gel (duodenum)
                                                        Diarrhea
       Stomach
                                        Environment – free
             Water and                  living cells or cells
             food intake                associated with:
                                        • Oysters
                                        • Plankton
                                        • Crabs
                                        •Crustaceum

Why was cholera chosen as a theme
     for the bioterrorist exercise in
   September 2009, Tulcea, Romania?
• The results obtained in deciphering the natural
  infection with the Vibrio genus and the Romanian
  experience in the management of two epidemic
  types of cholera:
   – Tulcea, with a major evolution in the Danube
      Delta, through water intake (undrinkable )
   – ConstanŃa- Black Sea shoreline through
      infected food intake
• “It offers the documented answer to the question
  in the title.’’

VIBRIO CHOLERAE O139 INFECTION

           Origin of serogroup Cholerae O139

     Vibrio Cholerae serogrupul O139 has its origins in the
Bengal Gulf as a result of the genetic transformation
undertaken by different subtypes of the Vibrio genus under
the influence of environmental factors and in the presence
of the dominant etiological agent of the seventh Vibrio
Cholerae O1 pandemic, biotype ElTor.

• Progress achieved in understanding the
  natural history of the Vibrio Genus, sustain
  its unique, unitary and dynamic
  characteristics and its etiological
  dynamics which is majorly influenced
  by the association of environmental and
  climatic risk factors.

Vibrio Cholerae O139 seems to have been
     generated from the ElTor biotype through horizontal gene transfer;
    it has the virulence and pathogenic mechanisms of the O1
    vibrios; BengalVibrio Cholerae O139 is virtually identical to the
    dominant subtype of the seventh Vibrio Cholerae O1 biotype ElTor
    pandemic with two important differences: the production of a new
    lipopolysaccharide (LPS) and an antigenic capsular polysaccharide
    with immunological implications.

•   The existence of a capsule is not among the characteristics of the O1
    vibrios and it can explain the resistance of O139 subtypes to the
    human serum in vitro as well as the occasional development of
    bacteriemia with O139.

VIBRIO CHOLERAE O139 INFECTION

• Vibrio Cholerae O139 has been isolated in
  other geographical areas: Argentina and
  Mexico. That particular subtype is different
  from the one implicated in the Asian
  epidemic (it is negative in the CT test -
  Cholerae Toxin, genetically different and
  considered to have no potential for
  pandemic evolution).

WILL V. CHOLERAE O139 BE THE
DOMINANT ETIOLOGICAL AGENT
   OF THE EIGHTH CHOLERA
          PANDEMIC?

The spread of Vibrio Cholerae O139 in
    Bengal (1992-2005) (Albert, Nair )

• The conclusion is that it is difficult to
  argue based on facts that the possible
  dominant etiology of the eighth pandemic
  is O139 serogroup

• Lately, Vibrio Cholerae ElTor biotype has
  become more virulent, has increased its
  resistance to antibiotics and has caused
  severe clinical features, including in the
  South-Eastern Africa.

WHO recommendation
• Surveillance of the “double ethiology” of the
  current cholera pandemic (O1 biotype ElTor
  and O139).

CONCLUSIONS
• Natural bacterial competition, under the pressure
  of environmental, climatic factors and the
  consecutive genetic dynamics represent a real
  issue that needs to be taken under consideration
  in what the surveillance of the pandemic cholera is
  concerned and it is a piece of reality that we cannot
  ignore furthermore without exposing ourselves to the
  “reckon up of the biological-epidemiological cost” of
  ignorance.

CONCLUSIONS
• Our opinion concerning the evolution
  perspectives of the seventh and eighth
  cholera pandemic is based on the fact
  that for centuries the pandemic
  evolutions of cholera as well as the
  etiological dynamics have had theirs
  birth in the Bengal Gulf, India and
  Bangaldesh, areas in which cholera
  spreads endemically.

CONCLUSIONS
• The dimensions of the seventh epidemic and the
  evolution perspectives of cholera infection sets it
  among the most important and constant pandemics.
• There is a possibility for less realistic appreciation
  determined by the fact that it is situated in areas and
  with a special structure of populations that may
  diminish the danger of global spread of cholera.
• V. Cholerae infection may surprise not only as a public
  health issue but also as a biological weapon.
• Bioterrorists don’t and won’t hesitate to use the results
  from scientific research as biological weapons.