EMERGING INFECTIOUS DISEASES
Volume 1, Number 4, October-December 1995

DISPATCH

(Pages 141-6)

Epidemic Cholera in the New World: Translating Field Epidemiology
into New Prevention Strategies

Cholera, a devastating diarrheal disease, has swept through the
world in recurrent pandemics since 1817. The seventh and ongoing
pandemic began in 1961 when the El Tor biotype of Vibrio cholerae
O1 emerged in Indonesia. This pandemic spread through Asia and
Africa and finally reached Latin America early in 1991 (1). After
explosive epidemics in coastal Peru, it spread rapidly and
continues throughout Latin America (Figure 1 cannot be viewed in
ASCII). Because of underreporting, the more than 1,000,000 
cholera cases and 10,000 deaths reported from Latin America 
through 1994 (Table 1) (2) represent only a small fraction of 
the actual number of infections. Molecular characterization of 
V. cholerae O1 strains from Peru has shown that they do not 
match strains from anywhere else in the world; therefore, the 
source of the Peruvian epidemic strains remains unknown (3). 
Moreover, other strains have since
appeared in Latin America. At least one of these, a strain
resistant to multiple antimicrobial drugs, was first identified
in Mexico and elsewhere in the world in mid-1991 and has since
spread widely throughout Central America (4). The introduction of
strains into new areas illustrates the rapid global transfer of
pathogens. V. cholerae O139 Bengal, which emerged as a new cause
of epidemic cholera in Asia in 1992, could also appear in Latin
America (5).

Such introductions are not easy to prevent, because they may
follow the arrival of travelers who are not aware of their
infection or of ships carrying contaminated ballast water. The
key to controlling epidemic cholera lies in limiting its spread
by using measures that prevent sustained transmission. One
measure might be using an inexpensive and effective vaccine to
provide lasting protection; however, no such vaccine yet exists,
although progress in vaccine development is being made (6-8).
Another measure is interrupting transmission so that the
causative organism never reaches the human host. This approach to
prevention successfully controlled many epidemic diseases in the
industrialized world, including cholera, typhoid fever, plague,
and malaria, before vaccines or antibiotics were developed. Over
the last century, a large engineering infrastructure, built in
industrialized nations, has provided safe water and sewage
treatment for nearly all people in these nations and has made
sustained transmission of cholera in those countries extremely
unlikely. Despite sporadic cases along the U.S. Gulf Coast and
repeated introduction of the epidemic organisms by travelers,
epidemic cholera has not occurred in the United States since the
nineteenth century (9,10).

To prevent cholera by interrupting transmission of the organism
to the host, it is important to understand precisely how the
bacteria are transmitted. John Snow demonstrated waterborne
transmission of cholera during a large epidemic in London in 1856
(11). He and many others since have suspected that other routes
of transmission are also important. Epidemiologic investigations
during the seventh pandemic have documented a variety of specific
food and water pathways by which the bacteria reach the host,
some of which were new and unsuspected (12). The El Tor biotype
of V. cholerae O1, for example, multiplies rapidly in moist foods
of neutral acidity (13). This bacterium also persists in the
estuarine environment in niches that are poorly understood but
may involve the plankton on which shellfish feed. This means that
raw seafood can be contaminated naturally before it is harvested.
Understanding these pathways of transmission in detail has been
central to devising successful control measures to block them.
For example, advice to drink only boiled or bottled water would
be of little use in outbreaks where the source was actually
contaminated food, such as shellfish or leftover rice. On at
least one occasion, such advice actually worsened the situation
because the bottled water was itself contaminated (14).

When epidemic cholera appeared in Latin America, after an absence
of more than 100 years, we conducted a series of eight rapid
field investigations in collaboration with national public health
authorities and the Pan-American Health Organization to define
the pathways of disease transmission and the priorities for
prevention. Conducted in various settings between February 1991
and August 1993, these investigations guided the initial
emergency prevention efforts and the development of sustained
prevention measures (Table 2) (15-21). 

The same case-control method was used for each investigation. We
first interviewed a few patients in great detail about what they
had ingested in the 3 days before they became ill, probing for
known or potential vehicles of cholera. We then constructed a
standardized interview questionnaire that asked about possible
exposures. Using this questionnaire, we interviewed patients
recovering from cholera as well as healthy persons of the same
age and sex who lived in the same neighborhood. By comparing the
frequency of positive and negative responses among the ill and
well persons, we could identify the exposures most strongly
associated with disease. For example, if 25 of 35 patients, but
only 5 of 35 matched controls, reported eating sliced mango from
street vendors in the 3 days before the illness began, the
probability of observing this difference in proportions by chance
alone is 0.000045, and the ratio of the odds of exposure is 15, a
measure of the strong association between disease and consuming
sliced mangos. When disease is statistically associated with more
than one exposure, multivariate analysis can identify truly
independent risk factors. In the above example, "eating food from
a street vendor" would not be independent from "eating sliced
mango" if one usually got sliced mango from a street vendor. This
case-control method can be rapidly carried out in the field at
low cost. 

Investigations showed that cholera was being transmitted by
several distinct mechanisms. The predominant route of
transmission in a given setting depends largely on the degree of
sanitation already achieved. Therefore, a multifaceted approach
to prevention is needed. Emergency measures, such as advice to
boil drinking water or to heat all foods from street vendors, are
difficult to sustain because of their inconvenience and high
cost. Moreover, the cost of building large-scale water treatment
and sanitation systems is extraordinary, estimated at $200
billion for all of Latin America (22). The challenge of cholera
prevention lies in devising low-cost alternatives that are both
effective and sustainable.

Waterborne transmission was identified in seven of the eight
investigations. In three of these, the implicated water came from
municipal systems or from tanker trucks that reportedly obtained
water from municipal systems. Water delivered through poorly
maintained municipal water systems can be contaminated by sewage
because of leaky pipes, frequent pressure drops, and the lack of
residual chlorine disinfectant in the water. In developing
countries, water is rarely available 24 hours a day so it is
usually stored in the home, where further contamination can
easily occur. For example, when we measured the increase in
contamination of the water as it was distributed and stored in
Trujillo, Peru, fecal coliform counts, an index of sewage
contamination, were 1/100 ml in water collected at the source
well, 2/100 ml at public taps, and 20/100 ml in water stored in
the home (13). In four investigations, the implicated water was
collected from rivers or ponds, where direct sewage contamination
was likely. Specific protective practices were also noted in
these investigations, including treating water in the home by
boiling it or by adding chlorine bleach, using a small-mouthed
vessel to store water, pouring water out of the storage vessel
rather than scooping it out with a cup, and having hand soap in
the home. In one investigation on the Amazon, we found that the
local common practice of adding citrus juice to water to improve
its taste was protective because the acid in the fruit killed
Vibrio bacteria (14). This observation gave local authorities a
new, inexpensive, and immediately available emergency control
measure.

The first stage of prevention, then, is providing safe drinking
water. As a result of the above findings, we have developed and
are testing simple and inexpensive methods of domestic water
disinfection and storage that would also prevent other diseases
transmitted by the same route. A pilot trial in a periurban area
of Bolivia showed that disinfecting household water with a
calcium hypochlorite solution and storing it safely in a special
narrow-mouthed container was acceptable to a community of Aymara
Indians (20). Compliance, as measured by chlorine residuals in
stored water, was high among families using the intervention. The
concentration of Escherichia coli bacteria in the stored water, a
measure of fecal contamination, was significantly lower in
households that used the intervention than in neighboring
households that used traditional water handling methods (23). A
field trial in rural Bolivia showed that villagers could generate
their own disinfectant solution by using a simple electrolytic
apparatus (24); with the disinfectant and the special water
container the villagers provided clean water in their homes.
Households using this intervention had 40% fewer diarrheal
episodes than randomly selected neighboring families who used
traditional water-handling methods. The combination of
point-of-use disinfection and safer water storage containers
could have broad effects, including local empowerment for
production of potable water, safer infant foods, and new
microindustries for the production of disinfectant solutions and
water vessels (25). Cost-benefit analysis indicates that this
strategy is cost saving if it prevents more than 20% of diarrheal
illnesses (26). Inexpensive disinfectant generators are now being
manufactured for this purpose in Ecuador. In Colombia, the number
of cholera cases has dropped dramatically since late 1992 when
chlorine disinfectant tablets were distributed for treating
household water.

The second major route of cholera transmission is food
contaminated in the market or home. This includes food and
beverages sold by street vendors, leftover rice, and unwashed
fruits and vegetables. This was an important route in four of the
eight investigated areas, including Guatemala City, where there
was no evidence of waterborne transmission (21). Foods and
beverages sold by street vendors are a fixture of urban life
throughout the developing world; they are often prepared in
unhygienic ways and then held at ambient temperatures for hours,
which permits rapid bacterial multiplication. Other problems
associated with food and beverages from street vendors included
using unsafe ice to chill beverages and selling homemade frozen
drinks. Leftover rice is an excellent growth medium for V.
cholerae O1 and eating leftover rice without reheating it was
associated with illness in three investigations. In one
investigation, illness was associated with eating unwashed
produce that was probably splashed with river water while being
transported to market in small boats.

Thus, the second stage of cholera prevention is to improve food
handling, particularly for foods and beverages sold by street
vendors. Many countries in Latin America have begun educating
street vendors in fundamental food safety and linking this
education to licensing (27). By itself, however, education may
not improve food safety if clean water to prepare foods and
beverages is not available and handwashing and dishwashing with
soap and water are not routine. We are field testing a combined
strategy of point-of-use disinfection, handwashing with soap, and
use of a special water/beverage container to improve the
microbial quality of beverages sold by street vendors. Because
street vendors are responsive to customer demand, teaching
consumers to look for street vendors that are visibly practicing
better hygiene may reinforce more hygienic conditions. In
addition to these efforts to improve food sold on the street,
health authorities should advise the public to reheat leftover
rice and wash fruits and vegetables before eating. In Santiago,
Chile, suspicion that cholera was caused by vegetables irrigated
with fresh sewage led to a ban on this practice; the ban not only
prevented cholera transmission by this route, but also decreased
the incidence of typhoid fever and hepatitis A dramatically (28).

Transmission through seafood (identified in two of the eight
investigations) is a third major route of cholera transmission,
distinct from other foodborne mechanisms, because it requires
different prevention strategies. One investigation implicated
both uncooked seafood and cooked crab, and another implicated
cooked seafood eaten without reheating. Contaminated seafood also
caused three outbreaks of travel-associated cholera in the United
States. In the most dramatic, at least 75 persons contracted
cholera after taking a flight from Latin America to California
(29); illness was associated with eating cold seafood salad that
was loaded onto the plane in Lima, Peru. Two other outbreaks
followed the informal transport of cooked crabs from Ecuador to
the United States in travelers' suitcases (30,31). Marine
creatures may harbor V. cholerae O1 before they are harvested or
may be contaminated by seawater used in seaside processing
plants. In areas where raw and undercooked seafood are popular,
seafood-associated cholera may occur even if the general level of
sanitation and hygiene is high (32). Vibrios survive light
cooking and can subsequently grow if the seafood is held for many
hours before eating (33).

Preventing seafood-associated cholera in the long term will
depend on maintaining sewage-free harvest beds and improving
sanitation in processing plants. In coastal areas where the
organism persists in the environment, even in the absence of
sewage contamination, education to discourage the consumption of
raw or undercooked shellfish is also needed. Thorough cooking
provides the greatest security, but it is sometimes resisted by
local populations for cultural reasons. "Ceviche," a popular
Latin American dish prepared from seafood that is marinated in
citrus juice for variable lengths of time, is a case in point.
Prolonged marination in acidic liquid is likely to inactivate
vibrios if the acid can penetrate throughout the flesh and deep
organs of the fish or shellfish (34). Further evaluation of this
approach is needed, but for the present, encouraging the use of
ceviche recipes that provide sufficient marination time may be a
practical intervention.

In Latin America, as in other parts of the world, epidemiologic
field investigations of cholera have defined the local routes of
transmission, identified unsuspected and correctable control
points, and quantified the effects of emergency measures. The
results of investigations also have generated specific control
strategies targeted to blocking the predominant routes. While
this multistage portrait of transmission is complex, it is being
translated into action and change. The longstanding deficits in
basic urban infrastructure and the need for new efforts to
correct them have never been more apparent (35,36). Workable
prevention strategies include better domestic water storage
containers, point-of-use water disinfection, attention to the
education and hygiene of street vendors, and simple modifications
of traditional recipes. Many other diseases are transmitted by
these same waterborne and foodborne routes, so these control
measures may prevent other infections in addition to cholera. If 
it becomes a catalyst for long overdue improvements in the safety
of water and food, epidemic cholera can have a far-reaching
impact on the public health of Latin America.

Robert V. Tauxe, M.D., M.P.H., Eric D. Mintz, M.D., M.P.H.,
Robert E. Quick, M.D., M.P.H.
National Center for Infectious Diseases, Centers for Disease
Control and Prevention, Atlanta, Georgia, USA

Table 1. Cholera cases by country, as reported to the Pan
American Health Organization, 1991 through 1994
                                          
                                 Number of reported cases         
                                 ______________________________
      
                Date of
Country        first report     1991      1992      1993    1994  
________________________________________________________________
Argentina      Feb. 5, 1992       0        553     2,080     889
Belize         Jan. 9, 1992       0        159       135       6
Bolivia        Aug. 26 1991     206     22,260    10,134   2,710
Brazil         Apr. 8, 1991   2,101     30,054    56,286  49,455
Chile          Apr. 12,1991      41         73        32       1
Colombia       Mar. 10,1991  11,979     15,129       230     996
Costa Rica     Jan. 3, 1992       0         12        14      38
Ecuador        Mar. 1, 1991  46,320     31,870     6,833   1,785
El Salvador    Aug. 19,1992     947      8,106     6,573  11,739
French Guiana  Dec. 14,1992       1         16         2     NR(a)
Guatemala      July 24,1991   3,652     15,686    30,605   4,227
Guyana         Nov. 5, 1992       0          5        66       0
Honduras       Oct. 13,1991      17        388     2,290   4,965
Mexico         June 13,1991   2,690      8,162    10,712   4,059
Nicaragua      Nov. 12,1991       1      3,067     6,631   7,821
Panama         Sept.10,1991   1,178      2,416        42       0
Paraguay       Jan. 25,1993       0          0         3       0
Peru           Jan. 23,1991 322,562    210,836    71,448  23,887
Suriname       Mar. 6, 1992       0          2         0       0
United States  Apr. 9, 1991      26        103        22      34
Venezuela      Nov. 29,1991      13      2,842       409       0

Total                       391,734    352,300   204,547 112,612
_________________________________________________________________
(a) NR = no reports received.
Source: ref. 2.

Table 2. Mechanisms of transmission of epidemic cholera in Latin
America, as determined in eight epidemiologic investigations, 1991-1993(a)

                     Peru           Ecuador   El        Bolivia  Brazil     Guatemala
          Trujillo   Piura  Iquitos Guayaquil Salvador  Saipina  Fortaleza  Guatemala City
          Urban      Urban  Urban   Urban     Rural     Rural    Rural      Urban
           3/91       3/91   7/91    7/91      3/91      2/92     6/93+     7/93         
           (15)       (16)   (17)    (18)      (19)      (20)      (b)      (21)
           
___________________________________________________________________________________________
Transmission
mechanism
____________________________________________________________________________________
    
Waterborne
Municipal   +         +                 +                      
water                            
   
Surface water                +                   +        +          +
                        
Putting            
hands in   +          +
water vessel               

Foodborne

Street vendors'       +                                                          +
foods                        
                                                                                
Street vendors'       +                 +                                        +
beverages                    
                                
Street vendors'       +                                                          +
ice/ices   
                                    
Leftover rice         +           +                                              +
                                            

Fruits/vegetables                 +          

Seafood                                      

Uncooked seafood                  +
    

Cooked seafood                    +           +            +
                                                
________________________________________________________________________________
(a)Reference numbers are in parentheses.
(b)CDC Unpublished data.

References

1. Centers for Disease Control. Cholera Peru, 1991. MMWR
1991;40:108-9.
2. Pan-American Health Organization. Cholera in the Americas.
Epidemiol Bull 1995;16:11-3.
3. Wachsmuth IK, Evins GM, Fields PI, Olsvik, Popovic T, Bopp
CA, et al. The molecular epidemiology of cholera in Latin
America. J Infect Dis 1993;167:621-6.
4. Evins GM, Cameron DN, Wells JG, Greene KD, Popovic T,
Giono-Cerezo S, et al. The emerging diversity of the
electrophoretic types of Vibrio cholerae in the Western
Hemisphere. J Infect Dis 1995;172:173-9.
5. Ramamurthy T, Garg S, Sharma R, Bhattacharya SK, Nair GB,
Shimada T, et al. Emergence of a novel strain of Vibrio cholerae
with epidemic potential in southern and eastern India. Lancet
1993;341:703-4.
6. Mekalanos JJ, Sadoff JC. Cholera vaccines: fighting an ancient
scourge. Science 1994;265:1387-9.
7. Sanchez JL, Vasquez B, Begue RE, Meza R, Castellares G,
Cabezas C, et al. Protective efficacy of oral
whole-cell/recombinant- B- subunit cholera vaccine in Peruvian
military recruits. Lancet 1994;344:1273-6.
8. Levine MM, Tacket CO. Recombinant live oral vaccines. In:
Wachsmuth IK, Blake PA, and Olsvik  , editors. Vibrio cholerae
and Cholera. Washington, DC: American Society for Microbiology,
1994:395-413.
9. Rosenberg CE. The cholera years: The United States in 1832,
1849, and 1866. Chicago: University of Chicago Press, 1987. 
10. Blake PA. Epidemiology of cholera in the Americas.
Gastroenterol Clin North Am 1993;22:639-60.
11. Snow J. On the mode of communication of cholera. The
Commonwealth Fund. London: Oxford University Press, 1936.
12. Mintz ED, Popovic T, Blake PA. Transmission of Vibrio
cholerae O1. In: Wachsmuth IK, Blake PA, and Olsvik O, editors.
Vibrio cholerae and cholera. Washington, DC: American Society for
Microbiology, 1994:345-56.
13. Kolvin JL, Roberts D. Studies on the growth of Vibrio
cholerae biotype El Tor and biotype classical in foods. J Hyg
(Cambridge)
1982;89:243-52.
14. Blake PA, Rosenberg ML, Florencia J, Costa JB, Quintino L do
P, Gangarosa EJ. Cholera in Portugal, 1974. II. Modes of
transmission. Am J Epidemiol 1977;105:344-8.
15. Swerdlow DL, Mintz ED, Rodriguez M, Tejada E, Ocampo C,
Espejo L, et al. Waterborne transmission of epidemic cholera in
Trujillo, Peru: lessons for a continent at risk. Lancet
1992;340:28-32.
16. Ries AA, Vugia DJ, Beingolea L, Palacios AM, Vasquez E, Wells
JG, et al. Cholera in Piura, Peru: a modern urban epidemic. J
Infect Dis 1992;166:1429-33.
17. Mujica OJ, Quick RE, Palacios AM, Beingolea L, Vargas R,
Moreno D, et al. Epidemic cholera in the Amazon: The role of
produce in disease risk and prevention. J Infect Dis
1994;169;1381-4.
18. Weber JT, Mintz ED, Caizares R, Semiglia A, Gomez I,
Semprtegui R, et al. Epidemic cholera in Ecuador: multidrug
resistance and transmission by water and seafood. Epidemiol
Infect 1994;112:1-11.
19. Quick RE, Thompson BL, Zuniga A, Dominguez G, de Brizuela EL,
de Palma O, et al. Epidemic cholera in rural El Salvador: risk
factors in a region covered by a cholera prevention campaign.
Epidemiol Infect 1995;114:249-55. 
20. Gonzales O, Aguilar A, Antunez D, Levine W. An outbreak of
cholera in rural Bolivia: rapid identification of a major vehicle
of transmission. 32nd Interscience Conference on Antimicrobial
Agents and Chemotherapy, Anaheim, 1992. Washington, DC: American
Society for Microbiology 1992; Abstract 937.
21. Koo D, Aragon A, Moscoso V, Gudiel M, Bietti L, Carrillo N,
et al. Epidemic cholera in Guatemala, 1993: transmission of a
newly introduced epidemic strain by street vendors. Epidemiol
Infect 1995; (in press).
22. de Macedo CG. Presentation of the PAHO regional plan.
Proceedings of the Conference: Confronting cholera, the
development of a hemispheric response to the epidemic; 1991 Jul
8-9; Miami: University of Miami, 1991;39-44.
23. Quick R, Venczel L, Gonzales O, Damiani E, Highsmith A,
Espada A, et al. Impact of narrow-necked water vessels and home
chlorination on fecal coliform and E. coli counts in drinking
water. 33rd Interscience Conference on Antimicrobial Agents and
Chemotherapy, New Orleans, 1993. Washington, DC: American Society
for Microbiology, 1993.
24. Quick R, Venczel L, Mintz E, Bopp C, Soleto L, Bean N, et al.
Diarrhea prevention in Bolivia through safe water storage vessels
and locally-produced mixed oxidant disinfectant. 35th
Interscience Conference on Antimicrobial Agents and Chemotherapy,
San Francisco, 1995. Washington, DC: American Society for
Microbiology, 1995; Abstract 1347.
25. Mintz ED, Reiff FM, Tauxe RV. Safe water treatment and
storage in the home: a practical new strategy to prevent
waterborne disease. JAMA 1995;273:948-53.
26. Miller M, Quick R, Mintz E, Tauxe R, Teutsch S. Solid stools
and solvent citizens: an effective solution for preventing
diarrhea in developing countries. 34th Interscience Conference on
Antimicrobial Agents and Chemotherapy, Orlando, 1994. Washington,
DC: American Society for Microbiology, 1994. Abstract 1244.
27. Arambulo P, Almeida CR, Cuellar J, Bellotto AJ. Street food
vending in Latin America. Bull PAHO 1994;28:244-54.
28. Alcayaga S, Alcagaya J, Gassibe P. Changes in the morbidity
profile of certain enteric infections after the cholera epidemic.
Rev Chil Infect 1993;1:5-10.
29. Centers for Disease Control and Prevention. Cholera
associated with an international airline flight, 1992. MMWR
1992;41:134-5.
30. Finelli L, Swerdlow D, Mertz K, Ragazzoni H, Spitalny K.
Outbreak of cholera associated with crab brought from an area
with epidemic disease. J Infect Dis 1992;166:1433-5.
31. Centers for Disease Control. Cholera New York, 1991. MMWR
1991;40:516-8.
32. Lowry PW, Pavia AT, McFarland LM, Peltier BH, Barrett TJ,
Bradford HB, et al. Cholera in Louisiana: widening spectrum of
seafood vehicles. Arch Intern Med 1989;149:2079-84.
33. Blake PA, Allegra DT, Snyder JD, Barrett TJ, McFarland L,
Caraway CT, et al. Cholera a possible endemic focus in the United
States. N Engl J Med 1980;302:305-9.
34. Mata L. Efecto del jugo y de la pulpa de frutas acidas sobre
el Vibrio cholerae. In: El Clera: Historia, prevencin y
control. San Jos, Editorial Universidad Estatal a Distancia -
Editorial de la Universidad de Costa Rica, 1992, 275.
35. Sepulveda J, Gomez-Dantes H, Bronfman M. Cholera in the
Americas: an overview. Infection 1992;20:243-8.
36. Witt VM, Reiff FM. Environmental health conditions and
cholera vulnerability in Latin America and the Caribbean. J
Public Health Policy 1991;12:450-63.