Download Vibrio cholerae: Ecology, Evolution and Climate

Vibrio cholerae: Epidemiology, Ecology,
Evolution and Climate Change
On Lee Lau
Abstract. With the advent of molecular techniques, such as PCR and genomics, it has been
possible to identify specific pathogenic agents and their characteristics; consequently, the
available literature on epidemics has increased exponentially. Here, I provide a basic guide
through the expanding literature and our understanding of the non-linear properties of cholera
emergence. The discovery and investigation of active cholera genes and toxins, bacterial
evolution and diversity, and molecular properties reveal mechanisms that we may use to improve
detection and population modeling of epidemics. In the case of cholera, biological and
mathematical information is critical in directing future policy for improving health resources and
education in specific areas, as new cholera biotypes continue to evolve, invade, and establish in
populated areas.
15 September 2004
Research sponsored by DARPA Grant DAAD19-02-1-0288, P00001
1 September 2004
Reed College, Portland, OR
DARPA Grant
Introduction
Vibrio cholerae bacterium has evolved in various coastal areas and is likely to become
infectiously active as temperatures increase during climate change. As the global temperature
increases, up to 2.6 C in the next 50 years as projected by the IPCC (1), the distribution and
ecology of many organisms are likely to shift according to their optimal performance. The
mysterious activation of the seventh pandemic, accompanied by the molecular change in a new
virulent biotype and persistence during recently prolonged El Nino years, suggests that cholera is
an active threat to challenge heath care capacities (2, 3).
The impacts of cholera in its second pandemic motivated modern health care in 1854,
with blocking the use of contaminated wells as directed by John Snow (3). Cholera is treatable
with rehydration and antibiotics. The history of cholera provides a source of biological
information to determine the mechanisms of transmission, persistence, and virulence. Recent
findings on molecular biology and ecology of Vibrio cholerae and clinical information of cholera
are herein reviewed in perspective of the historical knowledge that is basic to epidemiology.
During World War II, Japan released fleas infected with cholera and other pathogenic
organisms over China as a biochemical agent (10). The continued virulence of cholera
throughout human history attests to the flexibility of this gram-negative bacterium. Common
molecular elements producing CT, TCP, and RTX enterotoxin proteins and other observed
microbial characteristics help identify a population in water samples as the classical biotype V.
cholerae 01, the agent of previous pandemics. V.cholerae 01 El Tor was isolated as the seventh
pandemic. Recently, isolated in 1992, V. cholerae 0139, a non-01 pathogenic strain from
Indonesia, varies from El Tor strains in producing a distinct capsule and demonstrates the
bacterium’s ability to express pathogenic elements. It threatens to be the next pandemic. The
populations of these three toxigenic strains fluctuate with respect to each other, as emerging new
strains replace previous populations or cohabit (4). Over 206 serogroups are classified by the
identity of the somatic O-antigen.
Clinical evaluations of Cholera
Vibrio cholerae attaches to and colonizes intestinal lining. Cells affected by the cholera
toxin expel fluids. The infectious dose ranges from 103 – 105 cells, with a high dose being 108 (2,
3). Symptoms of cholera, namely watery diarrhoea and vomiting, generally occur abruptly after
an incubation period of between 18 hours and 5 days. The severity of cholera symptoms may
increase with a higher infectious dose, low host/local intestinal immunity, compromised gastricacid barrier, and blood group O. Severe cholera patients may lose 500-1000mL/h and 10% of
their body weight, and may die from volume shock (50% case-fatality) without treatment or
sufficient rehydration. Deaths from cholera usually occur in the first day. More commonly,
patients may fall into the other categories of none and some (or moderate) symptoms. Clinical
signs of dehydration become apparent after 5% loss of body weight. (3)
Many rehydration products have been developed to facilitate efficient treatment of
cholera symptoms. Emergency intravenous polyelectrolyte solution, commercially Ringer’s
lactate containing 4 mmol/L potassium and oral rehydration solution (ORS) containing 20
mmol/L potassium or 75 mmol/L sodium are given to prevent potassium deficiency as metabolic
acidosis is corrected. The same amount of fluid lost should be replaced within 2-4 hours. With
hydration, a patient normally recovers in 4-5 days. (3)
Antibiotics are effective in shortening recovery time to 2-3 days. However, cholera
resistance to tetracycline, ampicillin, kanamycin, streptomycin, sulphonamides, trimethoprim,
and gentamicin has been reported. A chromosomally integrating SXT element in V. cholerae
0139 may allow for resistance genes from neighboring organisms. Antibiotic resistance
undergoes fluctuating periods of sensitivity. (3) Antibiotics are not cost effective and
demonstrate the adaptability of the microbial community as well.
Improvements in Public Health
Transmission of cholera occurs through a combination of factors: seasonal bloom of
bacteria, contaminated water supply, inadequate sanitation, and contaminated seafoods. Water
filtration is an effective prevention of cholera as the bacteria inhabit copepods at an infectious
dose, 105 cells (2). A low cost filtration of folded sari cloth was introduced in a cholera-endemic
area with dramatic 50% reductions in seasonal cases (9). Rehydration products, various ORS, are
commercially available and widely used. Vaccines continue to be developed, with the latest
targeting identified virulent proteins, but vaccination is limited to 6 months effectiveness and is
therefore not practical for populations continually exposed to the evolving bacterium.
Fluorescence detection techniques are available for pre-infectious levels of V. cholerae. In the
1900s the US was successful in curbing cholera cases through the provision of safe municipal
water, especially in the New York area. Cholera is still endemic to areas in the southwestern
United States. There are seasonal outbreaks in those areas, especially when the surrounding
waters are compromised by pollution (8).
Genes and Toxins
Intensive study of toxigenic strains of 01 and 0139 yield a set of virulence genes most
notably belonging to TCP pathogenicity island, tcpA, tcpI, and acfB encoding colonization factor
TCP, and CTX prophage, ctxA encoding CT toxin (5,6). The investigation is far from complete
as more genetic variants to the proteins are found and bacteria continue to transfer genetic
components (4,6). The emergence of V. cholerae 0139 likely originated from a homologous
recombination event of environmental strain 022 O-antigen specific genes, which becomes the
0139 wbf region, with a 01 El Tor strain. V. cholerae 0139 and 01 El Tor strains share all their
virulence factors and similar ribotypes, from analysis of highly conserved rRNA (4). V. cholera
0139 strains are genetically highly diverse, with all combinations of nontoxigenic strains with
various virulence genes. Those with TCP+ genotypes may undergo toxigenic conversion by CTX
phage (4). Horizontally transferable conjugative transposons in V. cholerae or the presence of
integrons converting antimicrobial resistance of other organisms into functional operons may
explain the fluctuating antimicrobial character and genomic diversity of 0139. Genomic
instability probably contributes to the bacterium’s evolution and success.
Genetic diversity of proteins within individual V. cholerae explains the versatility of the
bacterium in different environments. V. cholerae contains two circular chromosomes (3, 6).
Chromosome II contains genes necessary for adaptation and growth in unique environments with
genes found to be active during human infection (5). In addition to gene clusters associated with
toxigenic strains, there are environmental alleles of virulence genes, which include some
environmental strains that are able to colonize and/or induce fluid accumulation by unknown
factors (6).
Life History and Persistence
In a severe cholera patient, up to 1013 bacteria per day may be released into the
environment (7); this release contributes to the continuance of an outbreak. V. cholerae can
survive in seawater for more than 50 days and may enter a viable but non-culturable state under
unfavorable conditions and cells may be resuscitated by heat shock (2). Association and
attachment with zooplankton, algae, and other aquatic organisms as biofilms is an important
aspect of V. cholerae life history to explore as developing policy may seek to control or
eliminate natural populations as a method of reducing incidence of cholera (11). As governments
and organizations develop policies to control the biological impact of previous policies that have
contributed to global climate change, it remains that V. cholerae is a part of the natural and large
oceanic ecosystem, and further understanding of the human-microbe interaction will yield
medically motivated public health changes and discoveries (12) that will benefit human
populations.
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