Rita Colwell: Global Infectious Diseases - Climate, Oceans, and Cholera
Berkeley Regents' Lectureship 2011
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see yesterday's talk http://ff.im/zt9tU
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she has defined many of the fields in environmental microbiology, particularly of the oceans
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decades ago, she was one of the first to identify that V. cholerae exists in free-living form in the oceans - this shows how ahead of the game she was
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very distinguished career in microbial taxonomy, physiology, and species interactions
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the first and only woman director of the National Science Foundation, appointed by Pres. Clinton, served there 6 years
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moving force that gave us biocomplexity, as well as putting together other transdisciplinary teams
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had huge effect on making more opportunities for women and minorities available
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she made the G-K-through-12 program, which is not being continued; we should write our representatives
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past president of AAAS, ASM, National Medal of Science
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a wonderful, warm, encouraging person to interact with
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now she begins
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"...whoever wishes to pursue the science of medicine must first investigate the seasons of the year and what occurs in them." -- Hippocrates, 4th century BC
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direct relationship between water quality and child survival: the less the fraction of the population w/ access to safe drinking water, the more deaths of children under the age of 5 (per thousand)
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total diarrheal diseases, in disability-adjusted life years (DALY), burden falls heavily on Africa, Asia, and S. America
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flagellated curved bacterium V. cholera grows on TCBS thiocyanosulfate bile salt (?) medium
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old cartoon shows specter of cholera haunting New York, until Wolman introduced chlorination of water in 1910
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John Snow made a map of the deaths from cholera, see _The Ghost Map_ by Steven Johnson, and supposedly removed the handle from the Broad Street Pump and ended the epidemic of cholera
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however, it actually took 20 more years, because the water commissioner refused to believe that his pump, which drew from the Thames (essentially a sewer), could be responsible
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cholera is not a disease of the past; we've all heard about Haiti
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Zimbabwe has experienced a cholera epidemic, starting in August 2008. A corrupt official took the money that was meant to be used for chlorinating the water. 10's of thousands of cases & deaths
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in 1970, Colwell showed that DNA from the bacteria isolated from the environment and DNA from bacteria isolated from patients would hybridize, using gradient centrifugation. This was not accepted by the medical community
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they also made monoclonal antibodies to pick up V. cholerae in a dormant state in the environment. this was also scoffed at, and the CDC referred to these as "Colwell's ghosts"
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micrographs of V. cholerae O1 entering into the VBNC state
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Dr. Takkaida (sp?) in Calcutta has used gas chromatography to isolate the components allowing V. cholerae to go from the dormant state into the growth stage
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used radio-labelled amino acids / carbon to show the bacteria were actively growing
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studied V. cholerae in Chesapeake Bay, 1998-1999, and studied relationship of environmental parameters such as salinity and temperature to incidence of V. cholerae in the environment
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zooplankton lay eggs in the water, and their axillae leak nutrients
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the bacteria also live in the zooplankton gut: a grad student did microsurgery on these copepod guts, excised them, and found the gut microbes almost entirely V. cholerae
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these copepods also occur in drinking water in Bangladesh
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the disease is dose dependent: mild diarrhea at 10^3 with antacids, severe diarrhea at 10^6 with food or >10^6 with water. thus responses vary
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multiple creatures in aquatic environment from which V. cholerae can be isolated
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see Carla Pruzzo et al, 2009. e.g., fish (host, vector), protozoa (host), benthic crustaceans (reservoir?), bivalve (vector ), etc.
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with colleagues at U. Dhaka, find other microscopic animals besides copepods harbor V. cholerae
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lots of cholera in Africa, but we usually think of it as Asia
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see book by Christopher Hanlon, _Cholera: A Biography_
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in Asia, have ponds where cholera is harbored; thus it is referred to as Asiatic cholera, but actually this is just because the clean drinking water has eliminated it in the US
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cholera has very rapid onset, within 24 hours. severe dehydration occurs. if rehydrated, within 36-48 hours, along w/ antibiotic, can be cured.
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A. Huq & R. R. Colwell have a model for cholera epidemiology: sunlight, *temperature*, nutrients, salinity, & rainfall in spring increase phytoplankton: micro- and macro-algae; then zooplankton, and finally an increase of V. cholerae in the water
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studies over 25 years in Bangladesh, Chesapeake Bay, Gulf of Mexico, Mexico itself, and Latin America at various times, have led to environmental parameters for the epidemiological model. pretty good fit, except in 2003 when the monsoon was unusually delayed
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in countries where sanitation is poor, have person-to-person transfer, but it's mostly in environment
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map w/ Sunderbans, in the Bay of Bengal, mangrove swamp, in W. Bengal India and Bangladesh. NIH grant to study cholera here
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the El Niño and the sea surface height affect the incidence of cholera. seasonal increases in spring & fall of plankton measured by chlorophyll, observed by satellite imagery
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over a series of studies from 1983 to the present, have shown relationship between cholera outbreaks in the Bay of Bengal and sea surface temperature measured by satellite. Will also measure salinity
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Constantin de Magny et al 2008, PNAS show model based on environmental parameters fits well for Kolkata and for Matlab (a city in Bangladesh)
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a simple, sustainable method for reducing cholera: They thought it would be useful to the individual villagers to take all this data and test a hypothesis: remove the zooplankton from the water to reduce the incidence of cholera. Use simple filtration.
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They tried both old saris and new saris. The old saris actually worked better, because they were beginning to unravel and thus formed better filters. The new saris were more regular and let more through.
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Applied and Environmental Microbiology, July 1996: 4 folds of sari cloth make an effective filter (nearly as much filtration as 8 folds)
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they also studied nylon filters, which were used in Africa despite being expensive, and compared with sari group and control group
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to be part of the study, the household had to have children under the age of five
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trained women as extension agent: explained why the filtration was important, gave them charts showing the zooplankton. they showed the women how to fold the sari, filter with it, unfold it, rinse it, and sun dry it to dehydrate it and act as a UV disinfectant
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not hard to convince the women that the water filtered through the sari cloth was better, it was much less turbid
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the sari cloth reduced cases by cholera by 50%, more than the nylon filter. also, they tracked down some of the sari filtered cholera cases, and found they had gone to visit other villages w/o sari filtration and contracted cholera there. PNAS 2003
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they went back 5 years later, and found 75% of the sari villages were still using sari filters, and 25% of the nylon villages were still using nylon filters, but 48% of the nylon villages were still using sari filters. some of the control villages had also heard about the filter and were also using them.
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herd effect: those with filtration in their neighborhood were less likely to get cholera
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in the year 2000, former Colwell student John Heidelberg postdoced at TIGR, and undertook to sequence first V. cholerae
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all Vibrio have two chromosomes, a large and a small, incl. luminescent bacteria related to the Vibrio's
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sequenced 23 V. cholerae from all over the world; 1910 from Saudi Arabia cholera case, 1937 from Indonesia cholera case,
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cases from US Gulf Coast, e.g., Louisiana: they go where the oysters are fat and sassy due to sewage outfall, harvest from there, and get one or two cases of cholera each year
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no two strains are absolutely identical; large variation within the species Vibrio cholerae
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greater variation between V. cholerae and other species
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can track evolution of V. cholerae by following strain-specific genomic islands, known major pathogenicity islands, and the genomic islands coding for O antigens.
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can show the variation in the clinical disease based on the strains that are dominant in the respective part of the world
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historically, it's been considered that the epidemic strain is the O1 serotype, and the others didn't have the pathogenicity island
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until 1992, to be diagnosed with cholera, had to be shown to have O1
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but in fact, the antigen used to diagnose the O1 serotype is laterally transferred, so have been tracking this gene, not the O1 serotype
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with cholera, have genetic shift and drift, just as with influenza virus and other pathogens
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it's been very difficult to get a reliable cholera vaccine. have variable backbone: may be hard to get a good vaccine if it's against antigens in the variable region, not present in the strains in the particular geographic region
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Haitian Cholera Epidemic 2010: on Nov 1, 2010, CDC issued a press release stating that based on pulsed field gel electroporesis (PFGE) of 13 Haitian isolates, these isolates are identical - the same strain and similar to a cholera strain found in South Asia
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this led Haitians to blame peacekeepers from Nepal for bringing cholera. that South Asian strain was one Colwell's group had sequenced and deposited in Genbank. if one used the whole genome, then removed the laterally transferred genes, the Haitian strains form their own clade separate from the Bangladesh 2002 VCCIRS101 strain
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Colwell's group has received permission and funding to ship TCBS plates to Haiti, and get 70 streaked plates from 70 different patients in 70 different places in Haiti. Have isolated V. cholerae O1 from 60 of them, and expect will have gotten sequence from 16 of them today. Also doing metagenomic analysis on water samples.
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the Haitian V. cholerae strains contain genotypes of a tight clonal complex, distinguish from Bangladesh, Zambia, and other strains
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SNPs separate CIRS101 from the Haitian strains
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study w/ Dr. Balakrish Nair, NICED, Kolkata. Every 5th patient admitted w/ diarrhea on 2 randomly selected days a week was enrolled. did classical (culture-based) and metagenomic tests for pathogens
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Vibrio, Aeromonas, Campylobacter, Shigella, Salmonella, EPEC, Rotavirus, Adenovirus, Norovirus, etc.
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of the samples taken, 43% had a single pathogen, and 29% had 2-6 pathogens, and some had no pathogen, by classical tests
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but of those with a sole pathogen by classical microbiology, a fraction had mixed pathogens by real time PCR. similarly, of 703 cases w/ no pathogen by classical microbiology, 54 had one or more pathogens by real time PCR
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also had matched controls of the cohorts, w/ no symptoms of disease. in the controls, found low levels of Shigella sonnei, E. coli O26, as well as other bacteria (Bacteroides, Lactobacillus, etc.)
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have algorithm to use on reads straight from Illumina, w/ no amplification and no hybridization, to identify the strains. were able to detect bacteria that are hard to identify by conventional means, e.g., H. pylori
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studying watershed area of Bangladesh: the Hooghly, the Ganges, and the Brahmaputra feed this river system
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Klein Goldewijk et al (2010a, b) have produced maps of population density in this area over more than a century
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density is high, so providing safe water to this part of the world is critical. have millions of people living in the delta. there is potential inundation of low elevation coastal zones, depending on by how many meters the sea level rises due to climate change
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if we provide safe water, we can protect against multiple pathogens. how many have had cholera vaccine? how many have had rotavirus vaccine? (not many) we're protected against these diseases
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protect national security and economic stability this way
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quotes John Muir: "when one tugs at a single thread, one finds it hitched to the rest of the universe"
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Q: so just taking zooplankton out of the water reduces incidence of cholera? what about sewage coming out of infected patients? A: the cholera is in zooplankton, but also in particulates and biofilm fragments. cholera is a dose-dependent disease. Q: so the human sewage is not that much of a contributing factor? A: in spring and fall, no. Q: does a mild case of cholera give immunity? A: the immunity is not lasting
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Q: suggest that contemporary vaccines are not very effective against cholera due to variation in strains? A: some of the vaccines, particularly the one from Sweden, are 80% effective. not saying that they're not effective, but suggesting--based on genomic data, don't have other evidence--that this variation in serotype might be taken into consideration. Q: so would have annual vaccine, like for influenza? A: this is being studied
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Q: would there be toxigenic V. cholerae in environment? A: theorize that osmoregulates copepods in the environment. in humans, it tries to help us osmoregulate but we end up with cholera. Q: so it's a disease of human progress, i.e., population density? A: have isolated V. cholerae from hydrothermal waters off Iceland, where they've never had cholera
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Q: relation with sea surface temperature? A: not just own work, but many years of work: temperature leads to increase in zooplankton, then the zooplankton population crashes, have large number of V. cholerae in the water
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Q: concentration of V. cholerae in the filtered water? A: from lab experiments, 90% of V. cholerae filtered out Q: so the planktonic V. cholerae concentration is very low, it's mostly particulates
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Q: would not recommend seafood from Chesapeake Bay? A: not if not properly cooked. have increasing incidence of Vibrio parahaemolyticus, e.g., in Alaska
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Q: distinction between groundwater and surface water in Bangladesh? A: the pumps get flooded, and the copepods don't need sunlight. there are copepods in the groundwater
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Q: how do the water bodies interact in that region of Bangladesh? showed individual ponds -- do they interact with the Bay on an annual basis? A: those are excavated ponds, and the houses are built out of the excavated earth. some of the ponds are connected to a river, and have a different microbial ecology than the ones that are distantly connected. however, in Sunderbans, flooding occurs annually. this saltwater flooding is ideal for Vibrio.
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