the global dimensions of cholera - home: centre on global ...cgch.lshtm.ac.uk/global dimensions of...

GLOBAL CHANGE & HUMAN HEALTH, VOLUME 2, NO. 1 (2001) 6 © Kluwer Academic Publishers

The global dimensions of choleraCholera remains among the most feared infectious diseases. The fi rst six pandemics of cholera, beginning in 1817, were

major public health emergencies, infl icting high morbidity and mortality across the world. Today we continue to battle

with the seventh pandemic that began in 1961 and shows no sign of abating. Of particular concern is the spatially and

temporally different epidemiological pattern of Vibrio cholerae O1 biotype El Tor cholera. Accompanying these worry-

ing signs is the emergence and spread of V. cholerae O139 Bengal in parts of Asia since the early 1990s. Cholera is

behaving differently and is serving as a barometer of the unhealthy global changes around us.

Kelley Lee

Centre on Globalisation, Environmental Change and Health London School of Hygiene & Tropical Medicine Keppel Street, London WC1E 7HT U.K. e-mail [email protected]

Cholera remains one of the most feared infectious diseases in public health. It is an acute bac-terial infection of the intestine caused by

the ingestion of food or water contaminated by certain strains of the Vibrio cholerae organism. V. cholerae produces enterotoxins (toxins which act in the gastrointestinal tract) whose actions on the mucosal epithelium is responsible for the character-istic symptoms of the disease, namely acute watery diarrhoea and vomiting. In the most severe cases, cholera is one of the most rapidly fatal illnesses known, due to severe dehydration or water loss. If left untreated, mortality from “classical” cholera can be 50%. A healthy person may become hypo-tensive within an hour of the onset of symptoms and may die within 2-3 hours although more usu-ally death may come within a day or so. Death in this way prompted the French to call cholera mort de chien (the dog’s death). With effective treatment, through fl uid and electrolytes replacement, mortal-ity can be reduced to less than 1%. Affected indi-viduals are highly infectious, contaminating water and food sources that they come into contact with. Therefore, the appearance of epidemic forms of cholera is treated as a public health emergency.

Until 1817, cholera largely remained a disease of South Asia. Epidemics of cholera-like diseases on the Indian subcontinent have been recorded from the early sixteenth century, and the history

of the disease goes back much further (based on references to deaths from dehydrating diarrhoea by Hippocrates and Sanskrit writings). From the nineteenth century onward, cholera spread to other parts of the world in seven pandemic waves. The fi rst six pandemics of “classical” cholera left in their wake high levels of morbidity and mortality, along with much social and political upheaval.[1,2] Each time, however, cholera retreated back to South Asia where it remains endemic to the present day. In 1961, a different strain of cholera, El Tor, spread from Southeast Asia to become the seventh pan-demic. Today, we continue to battle with this sev-enth pandemic which shows no sign of abating. An eighth pandemic may be waiting in the wings, again a new strain of cholera known as V. cholerae O139 Bengal that is slowly spreading across parts of Asia.

Since the isolation of the infectious agent by Robert Koch in 1883, we have continued to stead-ily advance our knowledge of the disease. We have mapped the entire DNA sequence of Vibrio chol-erae [3], learned how the O1 strain evolved to become lethal, and improved treatment, including use of antibiotics, despite growing antimicrobial resist-ance.[4]

The continuing challenges of cholera in the early twenty-fi rst century are integrally linked to the nature of the global changes around us. Processes

feature

GLOBAL CHANGE & HUMAN HEALTH, VOLUME 2, NO. 1 (2001)7© Kluwer Academic Publishers

Figure 1 Boy washing dishes in polluted irrigation canal in the Philippines (Source: M/MC Photoshare, www.jhuccp.org/mmc).

of globalisation, and how these processes are affect-ing the broader determinants of health including our social and natural environments, are core fac-tors in the way cholera itself has changed. Global technological, economic, political and environmen-tal changes are invariably intertwined and cannot be separated from the epidemiology of the disease. This raises clear implications for how we think about infectious disease control amidst globalisation, and the actions needed to put the protection of public health more centrally at the heart of global govern-ance.[5,6]

Cholera in historical context: a barometer of inequityCholera, particularly, lends itself to historical anal-yses because it is the fi rst disease for which modern public health surveillance, monitoring and report-ing was undertaken in an organised way. As a highly infectious and, in the nineteenth century, extremely lethal disease, it was included as one of a handful of

diseases (along with plague, yellow fever, smallpox and louse-borne typhus) regulated under the fi rst International Sanitary Regulations (known today as the International Health Regulations). Thus, his-torical records allow us to analyse trends over a rel-atively long time period and compare them with more recent trends in incidence and mortality.

Cholera was confi ned to the riverine areas of the Indian subcontinent since at least the early six-teenth century. There were occasional outbreaks along China’s coastal communities from contact with trading ships from South Asia, and in the Middle East among pilgrims travelling to Mecca. It was a much feared disease and its devastating impact led to the creation of an Indian goddess of cholera, Sheetola.[7]

In 1817, cholera began to spread worldwide and over the next one hundred years, there were six pandemics (Table 1). Medical historians attribute this change to the colonisation of the region by

The global dimensions of cholera


Table 1 Dates of the fi rst six cholera pandemics

pandemic year

1 (6 years) 1817-1823

2 (12 years) 1826-1838

3 (16 years) 1839-1855

4 (11 years) 1863-1874

5 (15 years) 1881-1896

6 (24 years) 1899-1923

Table 2 Cholera cases and fatalities reported in PAHO region,

1991-1999

year number of number of number of

cases deaths countries

affected

1991 391 751 ~ 4 000 16

1992 352 300 1 692 20

1993 204 543 2 362

1994 195 574 1321

1995 85 802 837 14

1996 ~21 000 ~266

1997 17 760 225

1998 57 106 558 16

1999 8 126 103 12

Source Compiled from Pan American Health Organization,

1996; Tauxe R. et al. Epidemic Cholera in the New World:

Translating Field Epidemiology into New Prevention Strategies.

Emerging Infectious Diseases, 1995; 1(4):

European powers, resulting in intensifi ed migra-tion, socioeconomic restructuring of local commu-nities, and alterations to the natural environment. More specifi cally, under the impact of the Industrial Revolution, the character of European imperialism changed. Early European imperialism focused on a search for the riches of the Orient, and the estab-lishment of trading stations and strategic outposts in Asia and Africa to protect them. In the nine-teenth century, however, the enforced opening of the world to European (notably British) commerce was enacted. This occurred in Turkey and Egypt (1838), Persia (1841), China (1842) and Japan (1858). Hence, the movement of traders, military personnel, camp followers and immigrants between Europe and Asia increased substantially from the early nineteenth century. In South Asia, this inte-gration of the region into the British empire led to the construction of poor draining irrigation canals to raise cash crops (e.g. tea, opium), impoverish-ment of local peoples by land reforms and taxa-tion, and mass migration as a result of economic hardship. Cholera became endemic throughout the region, and then to spread beyond the region to Europe, Africa and eventually the Americas.[8]

In Europe, cholera found hospitable conditions for spreading far afi eld. European societies were undergoing signifi cant social and economic transi-tion, including growing levels of human migration, urbanisation, socioeconomic inequality, and inad-equate water and sanitation facilities. Military con-fl ict and social upheaval resulted in soldiers living in appalling, crowded conditions. They became effec-tive vectors of a variety of diseases including syph-ilis, tuberculosis, typhus and typhoid fever. The Crimean War (1853-1856), in particular, resulted in such high numbers of deaths from disease that

the ensuing scandal famously led to the organiza-tion of proper military nursing services by Florence Nightingale.[9] A substantial proportion of the pop-ulation living in the industrial slums of large cities or affected by military confl ict, lived in squalid con-ditions with poor access to clean water and san-itation. As a water-borne disease spread by the oral-faecal route, cholera became a regular visitor, resulting in hundreds of thousands of deaths during each pandemic. Mortality associated with “classi-cal” cholera was approximately 50%. The lack of scientifi c understanding of how the disease spread, the poorly developed public health systems and, perhaps most importantly, prevailing social atti-tudes and complacency towards the conditions of poor and vulnerable populations allowed cholera to return time and again.

Effective public health response to the disease was slow in coming. Even John Snow’s famous removal of the Broad Street pump in 1854 did not defi nitively change the prevailing attitude that cholera was due to immorality and lack of “proper habits”.[8] It was not until thirty years later, with Koch’s important work in isolating the bacillus Vibrio cholerae as the causative agent of cholera, that the inertia of government policy began to shift.



The development of public health infrastructure, and the growing use of epidemiological methods to understand diseases such as cholera, were together underpinned by wider social reforms to improve housing, nutrition and sanitation.

Cholera traveled to the Americas via intensi-fying migration to the New World. The speed of spread was dependent on contemporary modes of transport. The advent of the steamship and rail-way, in particular, sped the transmission of cholera across larger distances. Consequently, each subse-quent pandemic encompassed a larger area than the previous. Coinciding with these spatial pat-terns were burgeoning trade, migration, political and cultural links across the world, what Robert-son describes as the Incipient (mid eighteenth cen-tury to 1870) and Take Off (1870 to the mid 1920s) phases of globalisation.[10] The fi rst saw the begin-nings of the admission of non-European societies to “international society”, while the second saw a sharp increase in global forms of transportation and communication technologies. With intensifying (frequency) and extensifying (geographical reach) links among societies on many continents, cholera and other infectious diseases were spread more quickly and farther afi eld. Indeed, it was cholera’s clearly crossborder nature that made it a keen sub-ject of negotiation at the periodic International San-itary Conferences held between 1851-1911. Focused narrowly on minimising the impact of certain infec-tious diseases on fl ourishing international trade, standard practices for shared surveillance, monitor-ing and reporting of outbreaks were agreed upon by the leading powers of the day.

Eventually, major welfare reforms, improve-ments in basic living conditions, such as housing, sanitation and dietary standards, led to the virtual disappearance of cholera from most industrialised countries by the mid 1920s.

Cholera and contemporary globalisation: what is the seventh pandemic telling us?After each of the fi rst six pandemics, V. cholerae O1 classical retreated to South Asia where it remained endemic. Regular reports of cases con-tinued between 1923-1961, but pandemic cholera disappeared for 38 years. The seventh pandemic began in Sulawesi, Indonesia in 1961, this time caused by a different biotype, V. cholerae O1 El Tor (named after the El Tor quarantine camp on

the Sinai peninsula where it was fi rst isolated in 1905 from the intestines of pilgrims returning from Mecca). There is uncertainty as to why El Tor assumed pandemic form when it did, and why it has subsequently spread worldwide to replace the clas-sical biotype. One theory from evolutionary biology argues that, when sanitation improves, selection acts against V. cholerae O1 classical in favour of the more benign El Tor biotype. The more virulent and lethal classical biotype kills the host more quickly and, in doing so, shortens the period, reducing the opportunity for infection of other potential hosts. The lower virulence of El Tor results in less severely ill, thus more mobile, hosts capable of infecting others over a longer period of time.[11] By 1964, El Tor cholera had reached South Asia, become endemic in the region and largely replaced V. chol-erae O1 classical.

The behaviour of El Tor cholera over the next forty years t has been distinct from the fi rst six pandemics in a number of ways.[12] First, the sev-enth pandemic has behaved differently along the spatial dimension of globalisation. The pandemic has affected a more widespread and greater geo-graphical area, including regions which had always, or for a signifi cant period, been cholera free. The number of countries affected continues to increase, and it is becoming endemic in an increasing number of areas. Furthermore, the pattern of spread across geographical areas has not been linear, (spreading from country to country), but in some cases, has “hopped continents”, showing up unexpectedly in different regions of the world. Some of the major outbreaks over the past four decades have occurred in Peru in 1991, Soviet Union from 1961 onwards, and South Africa from August 2000.

The second important difference is that the sev-enth pandemic has demonstrated temporal differ-ences both in the speed with which the disease has spread and the duration of the pandemic. In the nineteenth century, cholera transmission traveled across countries and continents as quickly as people moved via prevailing modes of transport. In the twentieth century, of faster modes, reduced costs, and increased frequency of transport by airplanes, automobiles, shipping and high speed trains, have led to the disease travelling much faster rate than earlier. The longest previous pandemic was the sixth pandemic that lasted 24 years (1899-1923). As of 2001, the seventh pandemic has lasted forty years



Figure 2 Women and children bathing and washing clothes in a river in Bangladesh (Source: M/MC Photoshare, www.jhuccp.org/mmc).

and shows no sign of abating. Despite the advent of modern public health systems and effective treat-ments in many parts of the world, the number of cholera cases continues to grow. In the late 1990s, there was a dramatic increase in the number of cholera cases worldwide, with an almost doubling of cases between 1997 and 1998.[13]

An important determinant of the epidemiology of the seventh pandemic is due to the differences in the V. cholerae biotypes. Although V. cholerae O1 El Tor serotype Ibana is a less virulent strain than V. cholerae O1 classical, it causes a higher proportion of asymptomatic infections (1:30-100 compared with 1:2-4), and thus allows carriers to spread the dis-ease unknowingly through contamination of food or water. The duration of carriage after infection is longer for El Tor, the organism grows in many foods, survives longer in the natural environment (it is one of the most resistant to adverse environ-mental conditions), and shows a greater resistance to antibiotics and chlorine. It also lives in associ-

ation with certain aquatic plants and animals, so water is an important reservoir for infection.[14]

The nature of the social and natural environ-mental changes being created by processes of glo-balisation plays an important role in the spatial and temporal differences of the seventh pandemic. In particular, V. cholerae O1 El Tor has remained closely associated with poverty and deprivation with its poor sanitation and lack of access to clean water. In the Celebes Islands of Indonesia, poor sanita-tion because of overpopulation of urban peripher-ies, military operations, and other environmental disturbances, combined with certain cultural prac-tices (e.g. use of night soil) contributed to the local cholera epidemic in the early 1960s.[15] An analysis of four cholera outbreaks during the current pan-demic suggests that global changes are intimately linked to its continued public health challenge.



Cholera returns to Latin America

Cholera arrived, as a vulture, in one of the bleakest peri-ods of Peru’s contemporary history.[16]

After disappearing from the western hemisphere for almost a century, cholera was simultaneously reported in January 1991 in three coastal towns in Peru. The epidemic that ensued moved with “unprecedented speed and intensity”, according to WHO reports, with 12,000 confi rmed cases by mid February. The disease then traveled two thousand kilometers along the coast to Ecuador, reaching Colombia and Chile by March-April. By the end of 1991, there were nearly 400,000 cases and more than 4,000 deaths. By all accounts, the epidemic was a major public health emergency, with more cases reported in one year than total reported during the previous fi ve years. The cause of the ini-tial outbreak remains unclear and subject to some speculation. Many believe that the disease was transported to the region by a Chinese grain ship, the Feng Xian, which arrived in the Peruvian town of Chimbote to pick up a cargo of fi shmeal. With several ill and infected crew members on board, the ship released infected bilge water into the coastal waters. Vibrio cholerae then infected the local shell-fi sh that were eaten by people. The outbreak of El Tor cholera in the U.S. Gulf Coast is similarly thought to have arrived, in turn, by ships from Latin America.[17]

While this theory that transoceanic shipping was the initial cause of the outbreak is questioned by some, it is widely recognised that ballast water from shipping is a major culprit in the spread of aquatic species. As French writes, some 3,000-10,000 spe-cies are moving around the world on any given day in ship ballast. Wherever these waters are dis-charged, so too are these organisms causing, in some cases, serious threats to local environments. Examples of ship induced “bioinvasions” include the Atlantic jellyfi sh in the Black Sea and zebra mussel in the U.S. Great Lakes. The likelihood of such occurrences has undoubtedly been increased by the intensifi cation of trade links in the twentieth century, including the use of ever larger ships.[18]

As well as illustrating global interconnected-ness through trade, the outbreak drew poignant attention to the susceptibility of the communities affected. The coastal Peruvian towns of Chimbote, Piura and Chancay are located in a relatively eco-nomically developed area of Peru with particularly

close trading relations with Asia. Nonetheless, the towns are extremely polluted with toxic and biolog-ical waste from the fi shery industry. For example, Chimbote is described as one of the most polluted towns in Peru, with the fi shery industry discharging 1570 metric tonnes of waste into the bay daily and other industries dumping another 100 metric tons on adjacent lands daily.[16] Rapid population growth in Lima and other coastal cities has also exerted stress on the local environment, with demand exceeding the infrastructure’s capacity to supply clean water and sanitation.

There is extreme socioeconomic inequality in this region. Sixty percent of the Peruvian popula-tion (13 million people) live in poverty, with more than half living in “critical poverty” (unable to meet basic needs in housing, health and education) and three million living in “extreme poverty” (unable to purchase minimum daily nutritional requirements of calories and protein). The poorest 30% of pop-ulation earn less than 5% of national income. Some of the root causes lie far beyond the country itself. Economic problems of the 1980s led to the election of President Fujimori and the intro-duction of economic stabilisation measures (known as “Fujishock”) and the World Bank-backed struc-tural adjustment programme in 1990. The social consequences of such policies, and their dispropor-tionately adverse impact on the poor, are widely acknowledged today. Within 18 months poverty in Peru increased by 11%.[19] Over the past twenty years, urban dwellers’ access to safe drinking water declined from 72% to 24%. Government expend-iture on the public health system also fell signifi -cantly during this period from 0.23% of GNP in 1982 to 0.04% in 1992, and decreased six-fold over the previous year during the fi rst six months of the Fujimori government. Public expenditure on health care and disease prevention decreased from US$77 million in 1982 to U$2 million in 1990. As Panniset concludes, “The Peruvian case demonstrates that the power of OECD countries (exerted, in this case, through the World Bank and the IMF) to interrupt or promote Peru’s commercial and fi nancial rela-tions ultimately had an impact on the outcome of the epidemic. The exercise of this power affected governmental policies to confront the epidemic and caused further deterioration of social conditions.”[16]

An alternative explanation for the Peruvian out-break comes from research by Rita Colwell and



others who believe that global climatic changes may be responsible. She starts by challenging the rela-tionship between V. cholerae and the natural envi-ronment, arguing that “Cholera bacteria are part of the natural ecology; they are in the environment, and this wasn’t accepted by the medical community for years. They thought it was person to person, but it is much more complicated than that”.[20] Of particular interest is the sea current, El Nino, that comes from the north to the south along the South American coast in the Pacifi c Ocean. This takes place each year at the end of December and begin-ning of January. In 1991, this current produced a higher temperature than usual in that part of the Pacifi c Ocean. Warmer temperatures led to a higher than average phytoplankton bloom upon which zoo-plankton feed. A proliferation of zooplankton, in turn, can result in an increased number of vibrios carried on zooplankton. The outcome is an infec-tious load of V. cholerae that can infect people who drink water inhabited with zooplankton, or eat fi sh and shellfi sh that have eaten zooplankton. This may explain the simultaneous outbreak in different towns along the Peruvian coast and the time of year of the outbreak.[21] While the link between the El Nino and the 1991 outbreak is debatable, the cli-mate-induced disasters that befell Central America in the late 1990s, notably Hurricane Mitch, had a clear impact on number of cholera cases. The number of cases were declining again up to 1997, but there was a resurgence in 1998 with over 300% more cases than in the previous year. Peru, again, led the way with a major outbreak in the fi rst three months of 1998. By 1999 there was a decline of 86% in the number of cases reported.[22]

The consequences of the cholera epidemic have global dimensions. A transborder public health threat such as infectious disease has potentially widespread knock on effects. Government offi cials in Peru and then other affected countries moved quickly to downplay any public health risk from fi sh exports (the fi shing industry is one of Peru’s primary industries employing around 56,000 Peru-vians) and to tourists. Perhaps, most memorable is the now infamous gesture in 1991 by the then Peruvian minister of health to calm public alarm by eating a local raw fi sh delicacy (ceviche) on television. The broadcast had the opposite effect, however, when the minister subsequently developed cholera. Similarly, a fl ight from Buenos Aires and

Lima arrived in Los Angeles in March 1992 with 65 people ill with cholera. The incident triggered a high-level diplomatic exchange between the presi-dents of Argentina and Peru who argued over which country was to blame, both seeking to avoid having their countries labeled as unable to control the dis-ease.[23][24] Such unfortunate incidents did little to prevent major impact on the region’s economies. It is estimated that in 1991, Peru’s tourist industry lost US$150 million, and tourist revenue to the region fell by US$750 million,[25] shrimp exports declined by US$270 million, overall losses were estimated at US$770 million.[26] Within weeks of the out-break, the members of the European Community and many other countries introduced restrictive measures and even embargoes on many Peruvian imports. Some countries, such as the U.S., intro-duced measures beyond those recommended by WHO to protect public health. For countries already struggling fi nancially to provide basic public health services, the economic impact of the outbreak fur-ther undermined the capacity of governments to address the underlying socioeconomic causes of the epidemic in the longer term.

Cholera in Africa: the South African epidemic (2000-present)

A time bomb ticking away….[27]

The El Tor cholera pandemic reached Africa in August, 1970, with the identifi cation of the fi rst case in Guinea. The disease was most likely intro-duced by a symptom-free infected traveler return-ing from a cholera-endemic area in Asia, possibly as part of the massive population movement resulting from the war between Pakistan and India. The dis-ease spread quickly to 30 of the 46 countries in the region, resulting in more than 150,000 cases and 20,000 deaths. By 1990, Africa accounted for 90% of cases reported to WHO.[28] Particularly vulner-able has been the Horn of Africa, where almost all countries host refugees or have internally displaced populations. There is a high risk of cholera among these vulnerable populations because of poor san-itary conditions and overcrowding in temporary settlements. The worst outbreak was among Rwan-dan refugees in relief camps in Goma, Zaire, and resulted in 70,000 cases and 12,000 deaths.[29] In the late 1990s, the heavy rains and fl ooding, due to El Nino, affected cholera in the region, particularly in Kenya, Uganda, Somalia, Zanzibar and Mozam-bique. Poor hygiene and unsanitary conditions in



Figure 3 Panoramic view from the city of Huancavelica in Peru (Source: M/MC Photoshare, www.jhuccp.org/mmc).

poor communities contributed to cholera’s becom-ing endemic.

In South Africa, cholera has a seasonal pattern that appears to follow the ambient local patterns of rainfall and temperature. El Tor cholera was fi rst detected in South Africa in 1974, when it was brought to the country by migrant mine workers. The outbreak remained confi ned to a small number of mines, but subsequent outbreaks have been more serious. In October 1980, the fi rst case was detected in the KaNgwane area of the Eastern Transvaal, possibly from the same cause, and the ensuing epi-demic continued until 1987. How the disease sur-vives during inter-epidemic periods remains a point of speculation. Recently, South Africa experienced its worst cholera outbreak in twenty years, with the fi rst cases of the current epidemic appearing in August 2000. As of March 2001, almost 46,000 people had been infected, with more than 100 deaths. The disease has spread to all but one of South Africa’s nine provinces.

The root cause of this outbreak the local gov-ernment authority’s ceasing to provide free water to local residents. The new policy is a result of ongo-ing pressures on the government to reduce public spending as part of wider macroeconomic reforms. The policy included introducing a charge to very poor people living in a squatter settlement near the town of Empangeni. The settlement is not unlike many others in South Africa and other African countries that form from migrating populations seeking employment. Oftentimes these informal set-tlements are located near local rivers used for both drinking water and sanitation. In South Africa, about 80% of poor (largely black) people have no running water and a higher proportion have no toi-lets.[30] With reduced access to clean water, and increased use of open river water, the cholera epi-demic has spread rapidly.



A reversal of fortunes: cholera outbreaks in the former Soviet Union

The spread of cholera and other infectious diseases is the calling card of an economy in trouble.[31]

El Tor cholera reached the then Soviet region of Uzbekistan in 1965 through the importation of the disease from Afghanistan. Local outbreaks and sporadic cases continued to occur in Uzbekistan, Turkmenistan and regions of Russia until the late 1960s. Coinciding with the peaking of the global pandemic, between 1970 and 1977, cholera spread more extensively, with outbreaks in more than 80 regions of the country. Since 1977, the number of cases has declined, although outbreaks have occurred periodically in different regions.[35] In the 1990s, cholera continued to occur in the region amidst growing political and economic instability. During 1994, cholera returned to ten cities in south-ern and western Ukraine resulting in approximately 20 deaths, and putting about fi fty million people at risk. The number of cases has since decline again. In 1998, Russia reported 10 local cases; in 1999, Russia reported 3 local and 5 imported cases, while the Ukraine reported 2 local cases.

While the number of cholera cases in the former Soviet Union remains relatively low compared to Africa, Asia and Latin America, the disease can be seen as an early warning sign of the declining state of the public health system. Their nineteenth cen-tury experience with cholera led the countries of the former Soviet Union to improve water and sani-tation infrastructure. By the 1980s, however, this infrastructure was deteriorating. As Narkevich et al. observe, water supply and sewage facilities in most towns and villages are unsatisfactory. Envi-ronmental pollution has also been a major problem in the region. In some regions, cholera cases occur every year and virulent toxigenic cholera vibrios are recovered from surface waters.[32-35] Regions with particular climatic, geographical, sanitary and social conditions, as well as transient populations and territories bordering cholera endemic coun-tries are especially at risk. It is perhaps not surpris-ing, therefore, that in 1997, the Russian ministry of health reported that it isolated V. cholerae O139 bio-type (see below) in Moscow sewage.

Home again, home again jiggidy jig:

V. cholerae O139 Bengal as the eighth pandemic?Just as disruption of the social and natural environ-ment in South Asia led to the fi rst cholera pandemic

in 1817, it is from this region that the most recent changes to the organism have emerged to challenge the public health community. As described above, from the mid 1960s, V. cholerae O1 classical bio-type was steadily displaced in the region by V. cholerae O1 El Tor which, subsequently became endemic. In 1982, a new variant of classical chol-era emerged in Bangladesh, initially displacing, but eventually coexisting with El Tor cholera for almost a decade.[36] However, of even greater concern has been the emergence of V. cholerae O139 Bengal, the fi rst non-O1 strain of cholera that causes an epi-demic form of the disease. V. cholerae O139 was fi rst detected in Bangladesh in January 1993 at a gath-ering of Muslim pilgrims near Dhaka. During the spring and summer of 1993, the number of V. chol-erae O139 cases outnumbered those of the O1 sero-type, but were on the wane by the autumn. By the end of 1993, 170,000 cases, resulting in 2000 deaths. Heavy rainfalls were documented. as con-tributing to the high toll. Using a diagnostic serum developed in Japan, cases were detected in Thai-land, Malaysia, Nepal, Pakistan, Burma (Myan-mar) and China. Imported cases were reported in the US, UK, Japan, Korea, Hong Kong and Singa-pore. By 1994, fewer cases of V. cholerae O139 were reported, and the epidemic was essentially over by the end of the year. A single case was reported in Denmark in 1995. Then, in August, 1996, V. chol-erae O139 reemerged in Southern India (Calcutta, Vellore, Madras), causing severe cases. In 1998, the disease was again detected in India, Bangla-desh, Thailand, Pakistan and possibly Afghani-stan. Overall, the specifi c number of cases remains unknown because current reporting systems do not report V. cholerae O139 and O1 separately. None-theless, it is known that the disease has affected at least 11 countries in south and southeast Asia.

There are ongoing debates about the origins of this new cholera strain, but most attribute at least some causation to global changes impacting on the social and natural environments. There is specula-tion that O139, for example, evolved from El Tor in the highly polluted waters of the Bay of Bengal. With intense population pressures in large urban concentrations (e.g. Calcutta, Dhaka), intensifi ca-tion of farming to feed growing populations, and widespread poverty and inequalities in the region, tons of pesticides, millions of gallons of industrial waste and raw sewage, and millions of tons of chem-



ical fertilizers are dumped daily into local rivers fl owing into the bay. It was previously thought that pollution dumped at sea would quickly degrade as it sunk downwards, but there is growing evidence that microbes and other biological material can sur-vive “in suspended animation” in the ocean depths, capable of resurfacing via the food chain (plants and plankton to fi sh and shellfi sh to humans) or ocean currents.[37] This human-induced degrada-tion of the local environment is also leading, it is believed, to widespread changes in the coastal ecol-ogy. The creation of “hot systems”, in which muta-tions of V. cholerae are selected and amplifi ed under new environmental pressures may explain changes in classical and El Tor cholera and the emergence of V. cholerae 0139.[38]

An alternative environmentally-focused theory (described above in relation to the Peruvian epi-

demic) argues that patterns of cholera epidemics in South Asia can be linked to patterns of global climatic change. Human-induced climate change may be creating favourable conditions such as water temperature, nutrient concentration and plankton production, for the growth and reproduction of the bacterium. The El Nino-Southern Oscillation (ENSO) infl uence on climate is also considered an important factor.[39] Like the O1 serogroup, O139 is found in association with plankton in pond sur-face waters that serve as a reservoir for V. cholerae in the aquatic environment. Research on the coinci-dence of zooplankton blooms and cholera outbreaks in September and October support this hypothesis. Blooms in early summer are also associated with lesser outbreaks.[40] Similarly, using remote sensing, Lobitz et al. (2000) found that sea surface tempera-ture shows an annual cycle similar to the cholera

Vibrios are one of the most common organisms in sur-face waters of the world, occurring in marine and fresh-water habitats, and in associations with aquatic ani-mals. Cholera is caused by certain strains of the bacte-rium Vibrio cholerae, distinguished by antigenic variation among the different strains. O antigens divide strains of V. cholerae into 139 different serotypes. Until recently, strains classifi ed as O1 antigen were the only known

Box 1 Classifi cation of types of Vibrio cholerae strains strain that is virilent. V. cholerae O1, in turn, is divided into three biotypes: Ogawa, Inaba and Hikojima. Each biotype may display the “classical” or El Tor phenotype.

V. cholerae O139 Bengal is the fi rst non O1 strain that is known to cause epidemic cholera. Indeed, with a unique O-antigen existing populations have a lack of residual immunity and are thus more vulnerable to the bacterium.

139 serotypes of Vibrio choleraeSerogroup

O139 (Bengal) othersO1

ClassicalBiotype El Tor

OgawaSerotype Inaba Hikojima

A, BAntigens A, C A, B, C A, B A, C A, B, C

Ogawa Inaba Hikojima



case data.[41] Furthermore, sea surface height may be an indicator of incursion of plankton-laden water inland (e.g. tidal rivers) and correlates with cholera outbreaks.

One of the main concerns with V. cholerae 0139 is that it will spread beyond Asia to become the eighth cholera pandemic. Signifi cantly, most of the cases so far have been adults, indicating that human populations in areas where V. cholerae O1 is endemic has no previous exposure to the strain. Recurrent infections of cholera are rare because of local immune defenses. In heavily endemic regions such as South Asia, the number of El Tor cases is low among adults in comparison with that in chil-dren. It appears that V. cholerae O139 is genetically derived from El Tor because it produces indis-tinguishable symptoms. However, one of the key differences between the two strains is that O139 has new adaptive mechanisms, such as a thin cap-sular layer which increases its virulence and inva-sive properties. This change in antigenic structure means that there is no existing immunity and all ages are susceptible and, equally signifi cant, it allows the bacteria to survive and multiply for extended periods in surface water. Finally, V. chol-erae O139 strains display different patterns of anti-biotic susceptibilities from O1 isolates. Research suggests that antimicrobial resistance is progressing in both serotypes but in different patterns.

ConclusionsCholera remains among those infectious diseases posing a potentially serious threat to public health systems around the world in the twenty-fi rst cen-tury. Since 1991 around 120 countries have reported indigenous cases of cholera, nearly half of those countries during at least fi ve of the last eight years. It is a recurring problem in many areas and has become endemic in others. Cholera illustrates many of the increased health risks associated with the global changes taking place around us - large scale movement of people, changes to ecosystems from heavy pollution, human-induced climate change, rapid technological change, and economic and polit-ical instability. Widening socioeconomic inequali-ties within and between countries leaves over one billion people without access to clean water and 1.7 billion people with no access to sanitation serv-

ices. The lessons learned in industrialised countries from the great pandemics of the nineteenth century have not yet been applied to the world as a whole.

While the biology of cholera is among the best understood of that of infectious diseases, there is much that we still don’t know. Cholera is recog-nised as more complicated and durable than previ-ous thought, possibly existing permanently within the environment rather than only living a few days outside of the human intestine. The relationship between the organism and environmental condi-tions continues to be a subject of keen debate. An effective vaccine for the variety of strains now known, especially for V. cholerae O139, requires fur-ther development. Current disease reporting sys-tems do not distinguish between the O1 and O139 serotypes, thus making impossible precise epidemi-ological analysis of the different cholera strains.

The poor quality of data also arises from the close link between the global economy and cholera. Despite being one of three mandatory notifi able diseases under the International Health Regula-tions of WHO, it is widely accepted that there is substantial underreporting of cases. The main reason for this is the lack of desire by national gov-ernments to attract adverse publicity that would have negative political and economic consequences. The outbreak in East Africa in 1997-98, for exam-ple, led the European Union to ban fresh imports from Kenya, Uganda, Tanzania and Mozambique. Fish exports are the fourth largest foreign-exchange earner (US$34-52 million) for Uganda.[42] These are valid concerns and are not yet effectively addressed under current international law. The links between global economic change and cholera may also be usefully explored in relation to chang-ing patterns of agriculture, food production and other human activity. For example, Agarwal sug-gests that the distribution of cholera matches the geographical distribution of sugar cane, and sugar-cane harvesting synchronises with interepidemic periods of cholera epidemiology[43]. Does this sug-gest something about modern agricultural practices and disease epidemiology?

The epidemiology of cholera in the four regions described in this paper suggests that cholera is very much a global story, one that requires going far beyond traditional approaches to public health.



The author Kelley Lee is is Senior Lecturer in Global Health Policy and Co-director of the Centre on Glo-balisation, Environmental Change and Health at the London School of Hygiene & Tropical Medicine. After several years analysing the

World Health Organisation and United Nations reform, she has developed strong research interests around understanding the impacts of globalisation on commu-nicable and noncommunicable diseases. These include cholera, tuberculosis, HIV/AIDS, infl uenza and tobacco-related disease. She is chair of the WHO Scientifi c Resource Group on Globalisation, Trade and Health, and on the Steering Committee of the UK Partnership for Global Health. Her current work focuses on the global dimensions of tobacco control with a major project of 14 countries funded by the U.S. National Cancer Institutes, and on emerging forms of global health governance. Her most recent book (co-edited by Kent Buse and Suzanne Fustukian) is Health Policy in a Globalising World (Cam-bridge University Press 2001), and she is presently com-pleting “Globalisation and Health: An introduction” and “Globalisation and Health: Case studies” (Macmillan Press/Palgrave).

[13] World Health Organization. Cholera. In : WHO Report on Global Surveillance of Epidemic-prone Infectious Diseases. Communicable Disease Surveillance

and Response, Geneva, 2000.[14] World Health Organization. Cholera. Fact Sheet No.107, Geneva, Revised

March 2000.[15] Bruce-Chwatt L. Global Problems of Imported Diseases. Advances in Para-

sitology. 1973; 11: 86.[16] Panisset U. International Health Statecraft, Foreign Policy and Public

Health in Peru’s Cholera Epidemic. University Press of America, New York, 2000.

[17] Harvard Working Group on New and Resurgent Diseases. New and Resur-gent Diseases, The Failure of Attempted Eradication. The Ecologist. 1995; 25: 21-24.

[18] French H. Vanishing Borders, Protecting the Planet in the Age of Globaliza-tion. W.W. Norton & Company, New York, 2000.

[19] InterAmerican Development Bank. Socioeconomic Report - Peru . Wash-ington DC, 1992, pp. 199-201.

[20] Rita Colwell as quoted in Marston W. In Peru’s Shantytowns, Cholera Comes by the Bucket. New York Times. 2000; 8 December.

[21] Speelmon E, Checkley W, Gilman R, Patz J, Calderon M, Manga S. Cholera incidence and El Nino-related higher ambient temperature. JAMA. 2000; 283: 3072-3074.

[22] World Health Organization. Cholera, 1999. Weekly Epidemiological Record. 2000; 4 August, 31: 249-56.

[23] Cholera kills one and Fells Many on Flight. New York Times. 1991; 21 Feb-ruary: A12.

[25] The Guardian, 6 September 2000.[26] Cash RA and Narasimhan V. Impediments to global surveillance of infec-

tious diseases: consequences of open reporting in a global economy. Bulletin of the World Health Organization. 2000; 78(11): 1358-67.

[27] Schalk van Schalkwyk, South Africa Democratic Alliance Chief Provincial Secretary as quoted in Harvey M. Cholera Epidemic May Be Spreading to Rest of South Africa. WOZA Internet. 2000; 31 October. http://allafrica.com/stories

[28] Glass RI, Claeson M, Blake PA, Waldman RJ, Pierce NF. Cholera in Africa: lessons on transmission and control for Latin America. The Lancet. 1991; 338, 28 September: 791-795.

[29] Heymann DL and Rodier GR. Global Surveillance of Communicable Dis-eases. Emerging Infectious Diseases. 1998; 4(3): 1-5.

[30] Sidley P. Cholera sweeps through South African province. British Medical Journal. 2001; 13 January, 322: 71.

[31] Alexander Moroz, Head of the Ukrainian Parliament, 1994 as quoted in Ryan F. Virus X: Understanding the Real Threat of the New Pandemic Plagues. HarperCollins, London, 1996.

[32] Walberg P, McKee M, Shkolnikov V, Chenet L, Leon DA. Economic change, crime, and mortality crisis in Russia: regional analysis. British Med-ical Journal. 1998; 317, 1 August: 312-18.

[33] Tkatchenko E, McKee M and Tsouros AD. Public health in Russia: the view from the inside. Health Policy and Planning. 2000; 15(2): 164-69.

[34] Marmot M and Bobak M. International comparators and poverty and health in Europe. British Medical Journal. 2000; 321, 4 November: 1124-28.

[35] Narkevich M, Onischenko GG, Lomov JM, Moskvitina EA, Podosinnikova LS, Medinsky GM. The seventh pandemic of cholera in the USSR, 1961-89. Bulletin of the World Health Organization. 1993; 71(2): 189-96.

[36] Sanyal SC. Cholera in its present day scenario. Journal of the Indian Medi-cal Association. 2000; 98(7), July: 371-76.

[37] McKie R. Killer diseases lurk in the ocean depths. The Observer (London). 1999; 27 June.

[38] Epstein P. Emerging Diseases and Ecosystem Instability: New Threats to Public Health. American Journal of Public Health. 1995; 85(2), February: 168-72.

[39] Pascual M, Rodo X, Ellner SP, Colwell RR and Bouma MJ. Cholera dynam-ics and El Niño-Southern Oscillation. Science. 2000; 289, 8 September: 1766-69.

[40] Frischer R. Synopsis: Vibrio cholera O139 - Detection, Characterization, and Control. Child Health Research Project. 1998; 4, October: 1-6.

[41] Lobitz B, Beck L, Huq A, Wood B, Fuchs G, Faruque AS, Colwell RR. Cli-mate and infectious disease: Use of remote sensing for detection of Vibrio cholerae by indirect measurement. Proceedings of National Academy of Sci-ences. 2000; 97(4), 15 February: 1438-43.

[42] Wachira Kigotho A. European Union bans fi sh imports from cholera-struck eastern Africa. The Lancet. 1998;351,17 January: 194.

[43] Agarwal M. Cholera epidemiology. The Lancet. 1999; 353, 12 June: 2068-69.

References[1] Snowden FM. Naples in the Time of Cholera, 1884-1911. Cambridge Uni-

versity Press, Cambridge, 1996.[2] Kudlick C. Cholera in Post-Revolutionary Paris: A Cultural History. Uni-

versity of California Press, Berkeley, 1996.[3] Heidelberg JF, Eisen JA, Nelson WC et al. DNA sequence of both chro-

mosomes of the cholera pathogen Vibrio cholerae. Nature. 2000; 406, 3 August: 477-483.

[4] Ramamurthy T, Rajendran K, Garg P, Basu A, Chowdhury NR, Nandy RK, Yamasaki S, Bhattacharya SK, Takeda Y, Nair GB. Cluster-analysis and patterns of dissemination of multidrug resistance among clinical strains of Vibrio cholerae in Calcutta, India. Indian Journal of Medical Research. 2000; 112: 78-85.

[5] Lee K. Globalization - a new agenda for health? In: International Co-oper-ation in Health, McKee M, Garner P, Stott R, eds., pp. 13-30. Oxford Uni-versity Press, Oxford, 2001.

[6] McNeill W. Plagues and People. Anchor Press/Doubleday, New York, 1976.[7] Macnamara C. A history of asiatic cholera. London, 1870.[8] Watts S. Epidemics and History, Disease, Power and Imperialism. Yale Uni-

versity Press, New Haven, 1997.[9] Bray RS. Armies of Pestilence, The effects of pandemics in history. The Lut-

terworth Press, Cambridge, 1996.[10] Robertson R. Globalization, Social Theory and Global Culture. Sage,

London, 1992.[11] Nesse RM and Williams GC. Evolution and the Origins of Disease. Scien-

tifi c American. 1998; November: [12] Lee K and Dodgson R. Globalization and cholera: Implications for global

governance. Global Governance. 2000; 6(2): 213-236.

the global dimensions of cholera - home: centre on global ...cgch.lshtm.ac.uk/global dimensions of...

Documents