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- Ralph R. Frerichs, Professor Emeritus, UCLA Dept. of Epidemiology (June 28, 2013). INTRODUCTION On, January 12, 2010, Haiti was devastated by a large earthquake, with the epicenter being 16 miles west of the capital city of Port-au-Prince. Ten months later, cholera cases and deaths began to appear in the rural Artibonite Department, about 62 miles north of Port-au-Prince (1). The disease had not been present in Haiti for at least half a century, so the emergence of a cholera epidemic was a surprising development. As of November 30, 2011, the Haiti Ministry of Public Health and Population reported 6,942 cholera deaths since the epidemic began and a cumulative total of 515,699 cases of cholera. Hence, among all persons with purported cholera the case-fatality was 1.3%. The story of the emergence and impact of cholera in Haiti is similar to what Dr. John Snow faced in London in the mid 1800s. At that time, he observed multiple cases and deaths from cholera, hypothesized a waterborne route of transmission, and noted the important roll of both the River Thames and a local water pump. Others at the time supported the miasma theory, believing cholera was transmitted through the air. Snow's intention, in explaining the epidemiology of the disease, was to prevent future occurrences of cholera. Ultimately, Snow's view of the disease was proven to be right. In the 2010 Haiti outbreak, the disease also is having a devastating effect on the population. There is much talk of controlling the epidemic, including by the World Health Organization (WHO) and the United States Centers for Disease Control and Prevention (CDC). Yet many are wondering how the epidemic got started in the first place, since cholera had not been in Haiti for a long time. So far there have been no published reports of detailed investigations by epidemiologists on the recent origin of cholera in Haiti. Yet investigating reporters have been very willing to step into void, thereby attempting to fill the mythical "activist" shoes of John Snow. Two hypotheses have emerged, explaining how the cholera outbreak got started. The interest for etiology is how the first wave of cases came to be (i.e., primary transmission from a common source), rather than the many cases that followed (i.e., secondary transmission from a common source or propagating source). Such secondary transmission in Haiti from one person to another is not mysterious, in fact easy to understand in a country where river bathing and water consumption are common, clean water is not always available, and sanitary conditions remain problematic, especially following the earthquake. Therefore this narration will focus only on factors that may have caused the index (or first wave) Haitian case or cases. What follows was gleaned from news postings and professional references, but is not necessarily fact. Instead it is an attempt to stimulate further inquiry on origin, namely answering how the index case or cases came about. If such detailed investigation also leads to preventive action by the Haitian government or international organizations, then we can anoint the skilled investigator and activist as a modern "John Snow." There are two main hypotheses (and perhaps more) regarding the initial cause of the Haiti cholera epidemic. Both will be considered here. The first views Vibrio cholera as a human pathogen, brought to Haiti by outside persons and then spread via water and person to others in the country. The second views Vibrio cholera as an aquatic bacterium, residing dormant in costal waters, until the microbes were activated by climate changes. PANDEMICS Cholera is caused by a toxin emitted by a bacteria, Vibrio cholerae (2). Traditionally, cholera is viewed as a human disease, in which an infective dose of the organism is ingested and then passed to others via infected feces, traveling directly by touch from one person to another, or indirectly by contaminated food or water. This traditional view, however, has been expanded in the past quarter century, as noted below. During the 19th century, cholera spread repeatedly in 6 pandemic waves, moving from the Bay of Bengal to most of the world. During the first half of the 20th century, the disease was confined largely to Asia, except for a major epidemic in Egypt in 1947. The current worldwide occurrence of cholera -- termed the 7th pandemic -- started in 1961. Cholera of the El Tor biotype (i.e., the same biotype as in Haiti) spread worldwide from Indonesia, reaching the Asian mainland in 1963, and Africa in 1970. The disease has has remained epidemic in many countries of Asia and Africa. After nearly a century of absence,cholera reached Latin America in 1991, causing explosive epidemics in many countries, including Peru. By 1994, approximately one million cholera cases had been recorded in Latin America. While the 7th pandemic was underway, scientists began to recognize environmental reservoirs of cholera, including the coastal waters of the Gulf of Bengal and in the southern United States by the Gulf of Mexico. As noted by Cairncross, by the 1980sVibrio cholerae became viewed as not just a human pathogen spread from feces to mouth, but rather as an aquatic bacterium which can survive in coastal waters for long periods of time, and then infect humans (3, 4). In Haiti, the full description of the organism is Vibrio cholerae serogroup 01, serotype Ogawa, biotype El Tor, identified by the National Laboratory of Public Health in Haiti and confirmed by the United States Centers for Disease Control and Prevention (1). THE HUMAN CAUSAL HYPOTHESIS Cholera in 2007-2009 has been reported by the World Health Organization (WHO) as occurring mainly in Africa and Asia (5). One Asian country - Nepal - is in focus as a possible source for the cholera epidemic that is impacting Haiti.
While cholera may be spread from infected to susceptible regions by tourists or other travelers, imported food or imported water, this does not appear to have happened in Haiti. Instead, the organism is believed to have traveled from Nepal with United Nations peacekeepers heading to the Annapurna military camp in Mirebalais by the banks of the Meile river which feeds into Haiti's Artibonite river (6). Cholera has been endemic in Nepal, as shown above in the 2007-2009 world map. The most recent cholera outbreak had occurred in the Nepal capital city of Kathmandu on September 23, 2010, shortly before the troops left for Haiti, arriving between October 8 and 15, 2010 (7).
ORGANISM Cholera, as mentioned previously, is caused by a toxin emitted by a bacteria, Vibrio cholerae. FIRST EPIDEMIC WAVE When investigating an infectious disease outbreak, epidemiologists usually focus on the initial cases. They then use the incubation period of the causative organism to work backwards to estimate the probable exposure time and the location of the cases at the time of exposure. The incubation period for cholera is from a few hours to 5 days, but usually 2-3 days. Thus if a cholera patient was first apparent as a symptomatic case on October 20th, the likely time of exposure would have been on the 17th or 18th of October. If the patient waited a few days before coming to a medical provider, then the exposure time might have been 4-5 days earlier. In Haiti, the government reported the initial wave of cases on October 22, 2010 (9). Some occurred in Mirebalais where the Nepalese peacekeeping troops were stationed, and others down-river in the Artibonite valley, and still others in communities by the coastal waters where the river ends. No initial cholera cases, however, appeared to be found up-river from Mirebalais, supporting the notion that the source came from the Mirebalais area. Alternatively, the initial pattern of cases does not rule out a source in the coastal region, moving up-river to as far as Mirebalais via river transport and commerce.
Perhaps the most consistent source of data on the cholera outbreak comes from Hôpital Albert Schweitzer (HAS), an organization that serves the 300,000 people in the Artibonite valley. On October 20, 2010, the following blog-post appeared on the HAS website: "During the day yesterday (i.e., October 19), reports came in to us at HAS that there was a suspected outbreak of severe diarrhea and vomiting, with most of the cases in the Artibonite region. By the late afternoon, HAS began to accept an influx of such cases, all with similar symptoms, and we reviewed charts from Monday and Sunday (i.e., October 17-18) to identify possible earlier cases. A total of 30 patients had been received by the middle of the night on Wednesday (i.e., October 20), mostly adults and primarily male. The patients came from localities near the Artibonite River, and many reported that they had drunk water from the river. The regional director ... came to HAS and reported that there were many cases in Petite Riviere (i.e., in the mid-artibonite valley, down river from Mirebalais). HAS staff who had been to the hospital in St. Marc (i.e., coastal community near the termination of the Artibonite river) reported that there was a large crowd outside the hospital, with an estimated 60 patients there." (10) Later HAS reported the initial group of cholera admissions by day for the time period from October 17 to November 9, 2010 (11). Their graph suggests that the first exposure occurred near mid-October, shortly after the Nepalese UN peacekeeping troops came to their Mirebalais base.
MODE OF TRANSMISSION Since no publication has yet appeared of a detailed investigation by WHO, Haitian or CDC epidemiologists that addresses the mystery of how the cholera epidemic in Haiti got started, the mode of transmission for the origin of the Haiti cholera epidemic is not known. The roll of the Nepalese UN peacekeeping force is strictly conjectural, although reasonable. In the absence of scientific information, reporters have provided useful initial observations that raise issues not yet addressed by epidemiologists. Included in this section are some passages that have been published by Jonathan M. Katz of the Associated Press (12, 13). "The U.N. issued a statement on Tuesday (i.e., October 26, 2010) defending the base. It said the Nepalese unit there uses seven sealed septic tanks built to U.S. Environmental Protection Agency standards, emptied every week by a private company to a landfill site a safe 820 feet (250 meters) from the river. But those are not the conditions AP found on Wednesday (i.e., October 27). A buried septic tank inside the fence was overflowing and the stench of excrement wafted in the air. Broken pipes jutting out from the back spewed liquid. One, positioned directly behind latrines, poured out a reeking black flow from frayed plastic pipe which dribbled down to the river where people were bathing. The landfill sites, across the street, are a series of open pits uphill from family homes. Ducks swim and pigs wallow in pools of runoff. The pits abut a steep slope which heads straight down to the river, with visible signs where water has flowed during recent heavy rains. The people who live nearby said both the on-base septic tank and the pits constantly overflow into the babbling stream where they bathe, drink and wash clothes." (12) Outside experts were consulted by journalist Katz and their thoughts were included in a November 3, 2010 Associate Press posting (13). One comment by John Mekalanos, PhD, Professor and Chair of the Department of Microbiology and Molecular Genetics at Harvard University, provides a good summary for the "human causal" hypothesis. Interviewed by Katz by phone from Cambridge, Massachusetts, Professor Mekalanos said... "The organism that is causing the disease is very uncharacteristic of (Haiti and the Caribbean), and is quite characteristic of the region from where the soldiers in the base came. ... I don't see there is any way to avoid the conclusion that an unfortunate and presumably accidental introduction of the organism occurred." THE CLIMATIC CAUSAL HYPOTHESIS
In Haiti, the recent cholera epidemic was first evident in the communities along the Artibonite River. If the cholera organism was present, it might be found in the estuarine zone, at the costal border between the Caribbean sea and the Artibonite river. Living in areas in Haiti are shrimp-like copepods. Studies in other parts of the world have shown that Vibrio cholerae can live on copepods in a sustaining relationship, often for long periods of time (15). A more detailed of the estuarine zone near the Artibonite River is shown here. The port at St. Marc is currently the preferred port of entry for consumer goods coming into Haiti. Hence it could be the source of cholera-infected food, water or ship workers, coming from Africa or Asia. People living in and around the city could also be infected by consuming the shrimp-like copepods with the attached Vibrio cholerae. In Bangladesh villages, cholera cases had been reduced significantly when copepods were removed from the drinking water, pointing again to the causal relationship.(15) The climate causal hypothesis was mentioned to a reporter in late October 2010 by Professor David Sacks of the Departments of International Health and of Epidemiology at Johns Hopkins Bloomberg School of Public Health. At that point in time, the Haiti epidemic had just gotten underway. Specifically, Dr. Sacks stated... "Cholera is an environmental bacterium. It can persist in the environment for many, many years without any human infection. ... The most likely explanation (for the Haiti cholera outbreak) is a rise in temperature and salinity in the river estuaries around the Bay of Saint Marc in the Artibonite Department of Haiti. That area, 70 miles northwest of Port-au-Prince, is the epicenter of the current cholera epidemic" (16). Further support for the climate causal hypothesis was given by cholera-expert Professor Rita Colwell of both the University of Maryland and the Johns Hopkins Bloomberg School of Public Health. Dr. Colwell opined... "They have been fortunate in Haiti that for 50 years the conditions have been such that they haven’t had an intense increase in cholera bacterial populations. ... But they’ve had an earthquake, they’ve had destruction, they’ve had a hurricane. So the conditions would lead to a very high probability of an outbreak. ... I think it’s very unfortunate to look for a scapegoat. It is an environmental phenomenon that is involved. The reason we don’t know [the catalyst] is because the medical community is not receptive to climactic causation or correlation" (16) CONCLUSION Haiti has been impacted by a deadly epidemic, initiated perhaps by United Nations troops from Nepal coming for peace-keeping purposes. Or perhaps climatic changes took place that stimulated the growth of the cholera organism. The first hypothesis has a human cause that can be addressed with better management, including prior testing of foreign troops for the presence of cholera and other transmittable diseases. The second hypothesis is not so easy to address, since it involves complex climatic changes that are not always predictable. So which is true, or is there a third or fourth explanation? Digging and probing, writing his observations and then presenting them to public officials and professional colleagues is likely what Dr. John Snow would have done. Is there a modern "John Snow" out there who will provide further evidence, and share his or her conclusions in a professional publication? If so, we might then have a scientific explanation for the origin of this devastating epidemic, necessary for creating policies and actions to prevent similar epidemics. SOURCES
NEW DEVELOPMENTS
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Typically, an infective dose of the organism is ingested and then passed to others via infected feces, traveling directly by touch from one person to another, or indirectly by contaminated food or water. Some people, termed carriers, harbor the organism for several months without showing any signs or symptoms. Therefore infected troops showing no signs of fever or diarrhea could easily bring the organism to a new country as carriers. In Haiti, the full description of the organism is Vibrio cholerae serogroup 01, serotype Ogawa, biotype El Tor, identified by the National Laboratory of Public Health in Haiti and confirmed by the United States Centers for Disease Control and Prevention (1). This same organism was recently reported by Nepalese scientists in a Japanese professional journal to have caused cholera in Nepal from mid-June 2008 to mid-January 2009 (8). Both the Haitian strain and the Nepalese strain were susceptible to tetracycline and ciprofloxacin, and resistant to furazolidone and nalidixic acid. While Vibrio cholerae serogroup 01, serotype Ogawa, biotype El Tor is common in Asia, the recent presence of cholera in Kathmandu, timing of the troop movements, possibility of carriers, and similarity in antibiotic susceptibility adds support to the hypothesis of travel from Nepal to Haiti. 
The climatic hypothesis assumes that Vibrio cholerae is an aquatic bacterium which infects humans. As such it lies dormant in the costal waters for many years, including perhaps Haiti, until some event disturbs the local environment, leading to an outbreak of the disease (14). 
The city of Saint Marc, with population of about 160,000, is just South of the shown estuary, sitting next to the Bay of St. Marc. As mentioned earlier, Saint Marc was included in the first wave of cholera cases, presented both by the government of Haiti and 