Infectious Diseases in a Global Context

• Combating infectious diseases presents an opportunity for a multidisciplinary approach, combining medicine with scientific and technological capabilities, with broad implications for daily life quality
• Science and technology can potentially balance the world's inequities
• A global context frames all human health issues in the twenty-first century, based on:
  • Worldwide movement of people and goods
  • Recognition that earth processes operate globally
  • A dynamic international scientific enterprise
• Health encompasses an individual's complex relationship with the global environment
• In the modern world, bacteria and viruses travel almost as fast as money
• Globalization has created a single microbial sea washing over all of humanity, meaning there are no health sanctuaries
• Infectious diseases account for about one-quarter of all deaths worldwide, excluding diseases triggered by infections
• Diarrheal diseases, tuberculosis and malaria are classical infectious killers
• AIDS has emerged as the second leading cause of death in just two decades
• Infectious diseases are responsible for 63% of deaths in children
• Diarrheal diseases are the second most frequent cause of death for children under five
• International travel has skyrocketed in the past half century, with approximately 500 million international arrivals per year
• International arrivals have increased since the mid-1990s, especially in Africa and the Middle East
• Infectious disease is a moving target, affected by climate shifts that influence environmentally sensitive stages or vectors
• Ecosystems and pathogens do not respond linearly to environmental changes
• The understanding of cholera has evolved from a linear reductionist model to a more intricate picture
• The current characterization of cholera's ecology includes:
  • Global weather patterns
  • Aquatic reservoirs
  • Bacteriophages
  • Zooplankton
  • Surface-attached cells
  • Adaptable genome
  • The deep sea
  • The bacterium and its host
• The recorded history of diarrheal disease in India goes back 2,500 years
• Ancient Sanskrit texts allude to a severe illness speculated to be cholera
• Until the early nineteenth century, cholera was primarily confined to the Indian subcontinent
• Since 1817, western medical history has described seven global cholera pandemics that spread illness and death worldwide
• John Snow (1813-1858) observed a correlation between the disease and its spread, and the source of public water
• He published On the Mode of Communication of Cholera in 1855
• The treatise identified the fecal-oral route of human infection
• The treatise offered arguments centered around germ theory

Ecology of Vibrio cholerae

• Vibrio cholerae requires for salt for growth
• A suggestion that Vibrio cholerae's ancestral home is the sea, perhaps a deep-sea vent
• Sulfide chimney samples collected from undersea hydrothermal vents on the East Pacific Rise contained Vibrio species with significant similarity to Vibrio cholerae
• Vibrio cholerae has two chromosomes, one large and one small
• The sequencing data revealed that V. cholerae is versatile, able to live in several habitat types and infect the human gastrointestinal tract
• Report from Andrew Camilli and colleagues in 2002 stated when V. cholerae passes through the human gut, certain genes appear to greatly accelerate their activity, making the bacterium 700 times more infectious
• Lateral transfer of genetic material occurs in V.cholera
• Virulence genes are distributed in environmental strains of V. cholerae from various serogroups, providing an environmental reservoir of such genes
• Vibrio O139 serovar acquired DNA from other cholera strains in its environment

Vibrio cholerae's relationship to environment

• Isolating V. cholerae O1 from the environment is difficult due to competition with other serovars
• Bacterial viruses play a major role in the microbial ecology of aquatic ecosystems
• Lysogeny occurs more frequently in V. cholerae 01 El Tor and O139 strains than in O1 classical strains which imparts antibiotic resistance to the host bacterium
• Phage infection may lead to new toxigenic variants, and polylysogeny can occur
• Pathogens such as V. cholerae can exist in a viable state even though they cannot be cultured
• Anwar Huq and Rita Colwell established the ecological relationship of cholera and planktonic copepods in 1983
• Cholera's causative organism lives naturally in riverine, brackish and estuarine ecosystems, making it non-eradicable
• Endemic areas seasonality is associated with temperature and salinity, as well as interactions with copepods
• Two epidemic variants of V. cholerae, O1 and O139 serovars, preferentially attach to specific genera of copepods

Vibrio cholerae Capabilities

• Pathogenic Vibrio species attach the best to surfaces, indicating their autochthonous aquatic nature
• Eurytemora is more prevalent in the upper Chesapeake Bay
• Acartia is more prevalent in the lower Chesapeake Bay
• Adhesive ability is an important attribute of V. cholerae
• Cholera originally evolved commensally with marine animals, such as copepods
• Bacteria's ability break down chitin is vital in the ocean ecosystem
• Production by V. cholerae of a mucinase enables penetration of the mucus barrier covering the gastrointestinal epithelium
• Increased adhesion to intestinal epithelial cells occurs when Vibrio is ingested with seafood
• Virulence and infectivity depend on bacterial properties and environmental factors
• Bacterial biofilm formation enhances colonization by V. cholerae and serves to protect against stomach acid
• Biofilm formation, virulence factors, and bioluminescence are regulated by quorum sensing
• The salinity most favorable for V. cholerae is between 2 and 14 g/l
• Concentrations are higher in the northern part of Chesapeake Bay, where salinity is low, and when the weather is warmer
• Temperature and salinity conditions predict the presence of V. cholerae with 75.5 to 88.5% accuracy

El Nino and Cholera

• Cholera resurfaced in Peru in 1991 after a century of absence in Latin America
• Cholera recurs in Peru following a seasonal pattern, with the greatest number of cases in summer
• Study by Erin Lipp and others demonstrated that detecting V. cholerae follows ambient temperature increases
• Detection followed ambient temperature increases and coincided with or preceded annual outbreaks of cholera in summer
• Significant correlation between cholera incidence and elevated sea surface temperature occurred from between October 1997 and June 2000, which included the 1997-1998 El Niño event
• A possible early-warning system for cholera risk could be established for Peru and neighboring countries
• El Niño events and cholera outbreaks have increased since the 1970s
• Sea surface temperature and height, as well as plankton blooms, can be used to forecast outbreaks of cholera

Contributions of other Disciplines

• Other disciplines inform study infectious disease and provide insights
• Social science and human beings help the complete understanding relating to cholera
• Even the poorest households can remove cholera from drinking water with a sari cloth folded eight to ten times, becoming a 20-mm mesh filter
• Straining water through used sari cloth prevents ingestion of cholera bacteria because its holes are smaller due to being pre-owned
• Old sari cloth filtered out more than 99% of the V. cholerae attached to plankton
• In Matlab, Bangladesh a study was conducted for three years in 65 villages, where roughly half the people used sari filters
• In villages using sari filters the incidence of cholera roughly halved and severity of the disease also appears to have been reduced
• "Small-world networks" best depicted these three systems
• Air travel has enabled diseases to spread across the world quickly