Gerry Greenstone, MD

A commentary on : The scourge that never dies

Human actions play a large part in creating the conditions that allow cholera outbreaks to occur.

ABSTRACT: The study of cholera is n the field of infectious disease, Snow’s investigations eventually an instructive one that touches on cholera is one of the most instruc- implicated a particular pump in Broad many different fields, including Itive diseases to study because it Street as an important source of the microbiology, epidemiology, marine touches on several disciplines, in - outbreak. Even though the number of biology, climatology, waste man- cluding microbiology, epidemiology, cases was already declining as a result agement, and socioeconomics. We marine biology, climatology, waste of people leaving the area, Snow man- now understand much about Vibrio management, and socioeconomics. aged to reduce the number further by cholerae that was previously per- The study of cholera began in earnest meeting with local officials and hav- plexing and know more about the more than 100 years ago. In 1854, the ing the handle of the pump removed. organism’s ability to survive by colo- city of was in the grip of a Investigation eventually identified the nizing the gastrointestinal tract of terrible cholera outbreak affecting , an infected child named copepods. Today cholera outbreaks hundreds and killing dozens. At the Frances Lewis, whose mother was continue to occur throughout Africa same time the scientific world was throwing her soiled nappies into a and in other areas affected by war embroiled in debating the merits of cistern that was found to be connect- and poverty such as Iraq. Until we the germ theory (disease is caused by ed to the pump in Broad Street by combine our understanding of V. a specific organism) and the miasma chronic rot. cholerae with determination to erad- theory (disease is caused by poisonous Although Snow’s ideas were not icate the disease it causes, many will vapors in the air).1 immediately accepted, the establish- continue to suffer and die because Previously, in 1849, Dr ment gradually came to recognize the of this waterborne illness. had published an essay about his importance of his findings, and long investigation of an earlier London after his death Snow became known cholera outbreak that had convinced as the father of epidemiology. him water was the carrier and cause of this terrible illness. During the 1854 Microbiology outbreak he set out to prove his theo- In the same year that Dr Snow was ry. He went from house to house carrying out his studies in London, Dr tabulating who was sick, who was Filippo Pacini, an Italian microsco- healthy, and who had died. He then pist, found an organism in stool sam- correlated these data with information ples of patients with cholera. While about the water supply. During his investigation, Snow received valu- Dr Greenstone works as a family physician able support from a local preacher, in Surrey. He has long been interested in Reverend Henry Whitehead, and a infectious diseases and the history of local statistician, Dr William Farr. medicine.

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studying a cholera epidemic in Flo- ties, including resistance. with 87% of these occurring in Africa. rence, he showed clearly that cholera This factor in particular has made it Since 2007, cholera has also been sufferers had numerous such organ- difficult to produce an effective vac- reported from several parts of Iraq. isms in their stools and healthy people cine against cholera. did not. He described a “comma- Marine biology shaped bacillus” and named it “Vib- Epidemiology Dr Rita Colwell first discovered the rio.”2 In a series of publications, he Cholera probably originated in the relationship between the Vibrio organ- correctly described the basic patholo- Bengal area of India and then spread isms and a type of zooplankton called gy as involving a massive loss of fluid west across Asia in a series of pan- copepods, tiny crustacea that feed in the intestinal mucosa. Unfortunate- demics beginning in 1817.6 The first on phytoplankton.8 These copepods ly, his published findings were not six all began in India, have an exoskeleton shell composed widely accepted and he did not receive while the seventh began in largely of a polymer called chitin. The the recognition he deserved. Instead, 1961 in Indonesia and reached Peru in Vibrio organism possesses an enzyme Dr received credit for the 1991. This outbreak, caused by the called chitinase, which allows the bac- discovery when he confirmed Pacini’s strain, was especially virulent, teria to partially digest the exoskele- findings in 1884. By that time the and by 1994 over 1 million cases ton, thus using it as a source of nutri- scientific world was ready to accept with 9642 deaths were reported from tion. In addition the bacteria are able microorganisms rather than the so- 13 countries in Central and South to colonize the gastrointestinal tract of called miasmata as the cause of the America. Routes of transmission of the copepods. disease. However, Pacini did finally receive posthumous recognition in 1965 when the International Institute of Microbiology renamed the organ- ism in his honor as pacini 1854.3 Subsequent research has delineat- ed the role of V. cholerae in causing disease by describing several patho- Cholera has continued to be a 4 genic factors. These include the abil- menace throughout the world. In 2000, ity of the organism to survive gastric acidity, to penetrate intestinal mucus, 56 countries reported cases, with 87% and to withstand gut motility. Other of these occurring in Africa. factors identified include the organ- ism’s ability to form adhesins and TCP pili (which allow the bacterium to adhere to the intestinal cells) and to form the cholera toxin (which causes massive outpouring of fluid from the mucosa). While V. cholerae has around 200 serotypes, only two are pathogenic— 01 and 0139. Serotype 01 is further V. cholerae in this epidemic included While associated with the cope- divided into classical and El Tor “unwashed fruits and vegetables, con- pods, the Vibrio organisms can exist strains.5 The newer serotype 0139 taminated food from street vendors, in a dormant state, remaining viable has acquired genetic material from contaminated drinking water and but not culturable through ordinary other Vibrio species, probably through contaminated crabmeat transported in means. These viable non-culturable mechanisms such as transduction, luggage.”7 (VNC) Vibrio organisms can thus be whereby viral DNA is incorporated Chlolera has continued to be a protected while moving with the tides into the host bacterial genome and menace throughout the world. In and traveling significant distances. confers greater pathologic possibili- 2000, 56 countries reported cases, The pathogenicity of the copepod-

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associated bacteria depends upon dif- stronger in the last 20 years and pri- Socioeconomics ferent environmental factors, such as marily involves coastal areas where The link between socioeconomic water temperature, salinity, and acid - V. cholerae thrives. By comparing the conditions and infectious disease is ity. These conditions often exist in patterns of sea surface temperature well known, but no disease highlights estuarine areas where the bacteria can and sea surface height with blooms of this connection better than cholera. propagate effectively and cause out- Vibrio-bearing plankton, Colwell and A clean water source, good personal breaks. The association of VNC bac- colleagues have been able to predict hygiene, and safe waste disposal are teria with copepods explains some outbreaks of cholera. essential to preventing epidemics. But previously perplexing observations: these factors are a gigantic challenge the persistence of Vibrio organisms Waste management for millions of people living in pov- despite negative cultures, the frequent Throughout history the story of chol- erty around the world. Thousands of recurrence of outbreaks in certain era has been intimately tied to the communities in the nonindustrialized areas, and the simultaneous occur- story of human waste, which has also world simply do not have the re - rence of new outbreaks in different been closely related to the use of sources or infrastructure to maintain locales.9 water. In the early 19th century the these necessities of . population of London rose to 2.5 mil- According to Dr Robert Morris,12 Climatology lion through rapid urbanization and “around the world 1.1 billion people Flooding, increased rainfall, and high- industrialization. With this population lack access to improved water sources er aquatic temperatures—all common explosion the amount of human waste and 2.6 billion lack access to im - in a warming world—can lead to became overwhelming. Cities contain - proved sanitation.” increased epidemics of waterborne ed masses of excrement in cisterns and Indeed, as the world becomes diseases such as cholera and typhoid. cesspools, a situation worsened by more heavily populated many related Flooding greatly increases the chance open sewers harboring germs carry- factors are ensuring that diseases such that fresh water will be contaminated ing cholera, typhoid, and other water- as cholera may never be eradicated with waste products and sewage. It borne diseases. because of “urban migration with for- also interferes with the supply of clean Then in 1831 a cholera epidemic mation of huge unsanitary slums, water and can cause direct invasion of struck the city.12 The high-density increased long distance mobility and reservoirs by bacterial overgrowth. inner-city living combined with in- trade, changes in personal behaviour Another weather factor related adequate toilet and waste facilities and the terrible disruption of wars and to disease is El Niño, which is part provided a ready means for the V. conflict.”13 Even as cholera outbreaks of a larger phenomenon known as cholerae bacillus to spread through continue to occur throughout the ENSO—El Niño Southern Oscilla- the citizenry, infecting and killing world, the last several years have seen tion. In El Niño years, there is an east- thousands. By 1847 London’s sewage a concentration in Africa, especially ward shift of rainfall and warm water problem was even worse with more in Angola, Sudan, Zaire, Democratic across the equatorial Pacific Ocean excrement piling up in cesspits and Republic of the Congo, Senegal, and toward the west coast of South Amer- open sewers. Niger. ica along with a decrease in the nor- The first act of the newly formed In September 2007, a cholera out- mal upwelling of ocean nutrients in Metropolitan Commission of Sewers break was reported around Kirkuk that area. This warmer water along the was to close the cesspits, thus direct- in northern Iraq. Cholera has since Peruvian coast along with increased ing the sewage into the Thames River, spread to Baghdad and other areas, plankton stimulated by El Niño rains which essentially became a giant which is not surprising in a country appears to have increased the V. sewer. Since the river was also the where war and poverty ensure inade- cholerae population in the ocean.10 main source of drinking water, anoth- quate access to clean water, disruption The association of warmer water er major cholera epidemic occurred of sanitary networks, and the preva- and cholera outbreaks has also been the following year, killing thousands. lence of raw sewage.14 Although the observed in Bangladesh’s Bay of Ben- This epidemic indicated the impor- general situation in Iraq is improving, gal area, where the seasonal pattern of tance of separating the water intake continued outbreaks will occur until cholera reflects sea surface tempera- from the sewage output, a factor still adequate infrastructure and basic tures and plankton abundance.11 This crucial today in preventing cholera facilities are in place. relationship appears to have gotten outbreaks.

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Conclusions A review of the history of Vibrio cholerae shows us that cholera is not just a disease but a result of how we interact with the world around us. While the V. cholerae organism itself can never be eradicated, the disease it causes can be controlled. Thus, the morbidity and mortality of future out- If there is malnutrition there will be cholera; breaks depends not so much on the if there is poor sanitation there will be cholera; organism as on human actions and the environment surrounding the organ- if there is war there will be cholera. ism. If there is malnutrition there will be cholera; if there is poor sanitation there will be cholera; if there is war there will be cholera. We have the knowledge and the technology to eradicate this disease, but do we have the will and the deter- mination? If not, then cholera will remain the scourge that never dies. 5. Lipp EK, Huq A, Colwell RR. Effects of 10. Rodo X, Pascual M, Fuchs G, et al. ENSO Competing interests global climate on infectious disease: The and cholera: A nonstationary link related None declared. cholera model. Clin Microbiol Rev to climate change? Proc Natl Acad Sci 2002;15:757-770. USA 2002;99:12901-12906. References 6. Hays J. Epidemics and Pandemics: Their 11. Pascual M, Rodo X, Ellner SP, et al. 1. Johnson S. . New York: Impacts on Human History. Santa Bar- Cholera dynamics and El Niño-Southern Riverhead Books; 2006:57-76. bara: ABC-CLIO; 2005:98-116. Oscillation. Science 2000;289:1766- 2. Bentivoglio M, Pacini P. Filippo Pacini: A 7. Guthmann JP. Epidemic cholera in Latin 1769. determined observer. Brain Res Bull America: Spread and routes of transmis- 12. Morris RD. The Blue Death. New York: 1995;38:161-165. sion. J Trop Med Hyg 1995;98:419-427. HarperCollins; 2007:25-44. 3. UCLA Department of Epidemiology. 8. Colwell RR. Infectious disease and 13. Weiss RA, McMichael AJ. Social and Who first discovered Vibrio cholera? environment: Cholera as a paradigm for environmental risk factors in the emer- www.ph.ucla.edu/EPI/snow/first waterborne disease. Int Microbiol 2004 gence of infectious diseases. Nat Med discoveredcholera.html (accessed 2 Dec;7:285-289. 2004;10(12 suppl):S70-76. November 2008). 9. Colwell RR. A voyage of discovery: 14. World Health Organization. Outbreak 4. Klose KE. Regulation of virulence in Vib- Cholera, climate and complexity. Environ news. Cholera, Iraq. Wkly Epidemiol Rec rio cholerae. Int J Med Microbiol 2001; Microbiol 2002;4:67-69. 2007;82:321-322. 291:81-88.

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