This report provides comprehensive data on the first outbreak of E. coli O157 infections from the developing world. Drought, carriage of E. coli O157 by cattle, and contamination of surface water appear to have been important contributing factors. Given the extent of the outbreak, the multiple modes of transmission, and the likely recurrence of predisposing factors, the emergence of E. coli O157 has major implications for diarrheal disease control strategies in Africa.

Although the simultaneous occurrence of cholera in some areas where E. coli O157 infections were detected makes it difficult to definitively determine the magnitude of the E. coli O157 outbreak, national disease surveillance figures for Swaziland leave little doubt that a massive outbreak of diarrheal illness occurred there in 1992, and several lines of evidence suggest E. coli O157 played a major role.

First, the clinical presentation of illnesses at the plantation and of the initial patients at the refugee settlements is consistent with E. coli O157 infection. Symptomatic cholera infection almost always manifests as profuse watery diarrhea. Severe abdominal pain and bloody stools are very uncharacteristic for cholera but are the hallmark of hemorrhagic colitis caused by E. coli O157 (8-10). E. coli O157 can also present as nonbloody diarrhea (11,12). In a household survey performed during a waterborne outbreak of E. coli O157 infections in the United States, bloody stools were reported by only 35% of those with diarrhea (13). This figure is similar to the proportion of ill persons reporting bloody stools in the plantation survey (28%) and to that observed among the patients seen initially at the Malindza clinic (29%). It seems reasonable, therefore, to infer that some of the cases of nonbloody diarrhea, which were temporally and geographically associated with cases of bloody diarrhea caused by E. coli O157, represent milder manifestations of illness caused by this pathogen.

Second, medical personnel clearly recalled that there were two waves of diarrhea, dysentery followed by watery diarrhea, with each surge initially affecting different populations. (Although the term dysentery technically refers to the presence of blood and pus in stools, it is used here to mean nonwatery diarrhea, which may be bloody, accompanied by severe abdominal pain.) In a report filed November 27, 1992, following an assessment of the situation at Ndzevane, the World Health Organization (WHO) representative in Swaziland documented this impression, stating "the type of diarrhea [seen at Ndzevane among the refugees] appeared to be different from that noticed in the neighboring areas," i.e., among the Swazi nationals residing outside the camp (14). Although we suspect that cholera was the likely cause of much of the diarrhea during the second wave of illnesses at the refugee camps, we do not believe the initial dysentery outbreak among the local Swazi population can be attributed to this pathogen. (Although the term dysentery technically refers to the presence of blood and pus in stools, it is used here to mean nonwatery diarrhea, which may be bloody, accompanied by severe abdominal pain.)

Third, E. coli O157 was isolated from specimens collected from seven different diarrhea-affected foci that spanned a distance of several hundred kilometers. The actual area involved may have been even greater because in the months immediately following this outbreak, investigators in Malawi and Angola reported outbreaks of diarrheal illness in which nucleic acid amplification tests of stool specimens suggested E. coli O157 as the cause (15,16).

Estimates of the magnitude of the E. coli O157 outbreak ultimately depend on how one apportions the 64,699 consultations for diarrhea (all ages) in Swaziland during October and November 1992, after counterbalancing the identification of cholera in late November with widespread reports of dysentery in the local population and confirmation of E. coli O157 over an extended area. Even if E. coli O157 accounted for only a small proportion of visits, this would represent thousands, perhaps tens of thousands, of infections and one of the largest outbreaks of this agent in history.

Understanding the complex interaction of environmental and behavioral factors that enabled E. coli O157 to emerge so intensely in Africa is important for future diarrheal disease control efforts. Cattle are the major reservoir of E. coli O157 and shed this organism more frequently when stressed (17). This region had been experiencing several years of drought, a situation that worsened from July to September 1992. As the drought continued, cattle began to graze close to the remaining sources of surface water and vegetation. The marked increase in cattle deaths beginning in August 1992 indicates that available pastures and water sources were often insufficient.

Although the number of cattle decreased, demand for beef apparently did not. Nearly one quarter of persons surveyed on the plantation indicated that they had eaten beef from cattle known to have been found dead. Commercial beef slaughter and distribution practices were also affected by the shortage of cattle. Earlier in the year, cattle imports from South Africa to Swaziland were banned, a decision said to be supported by some ranchers because it enabled them to sell off dying animals (18). A senior health inspector noted that a single large abattoir was supplying meat to many butchers in the country since the drought and that "preventive health is not taken as a matter of priority by the look of things" at the abbatoir (19). Plantation staff also indicated, for the first time in their memory, that just before the outbreak some of the weekly beef rations were spoiled. Although adequate cooking temperatures will kill E. coli O157, much of this beef would have been grilled, leaving the possibility that portions remained undercooked.

Figure 6

Figure 6. . Cattle grazing in a trickling stream bed, Lubombo, Swaziland, 1992. The nearly ubiquitous hoof prints, visible in the foreground, indicate cattle often frequented the stream beds. Photo credit: Paul Effler....

How E. coli O157 originally found its way to cattle in southern Africa is not known, but once there it is not difficult to speculate on how it spread. Recovery of E. coli O157 from surface water in Swaziland and South Africa plausibly explains how this pathogen might be rapidly dispersed over vast stretches of land. According to local residents and our own observations, during the drought, cattle often frequented the trickling streambeds, defecating and dying there (Figure 6). With the onset of heavy rains, water contaminated with cattle feces (and presumably E. coli O157) would have become readily available to both livestock and residents in villages downstream. Such a scenario is consistent with the epidemic curve from the sugar plantation outbreak; E. coli O157 has a median incubation period of 3 to 4 days, and the outbreak exploded 3 days after the first heavy rains in 4 months (10). PFGE results indicate that a single clone was responsible for much of the outbreak, suggesting that either there was an exceptionally narrow range of diversity among E. coli O157 isolates in south African cattle or that a single clone was able to expeditiously spread over large distances, perhaps via surface waterways revitalized by heavy rains.

By early 1993 we no longer detected E. coli O157 in patient stools or environmental specimens obtained from the affected area, intimating that the outbreak had ended almost as abruptly as it started. Since that time, however, two other outbreaks of dysentery have been attributed to E. coli O157 elsewhere in Africa, the first in Central African Republic in 1996, and the second in Cameroon beginning in 1997 (20,21). Both these reports have some constraints, however; in the Central African Republic, E. coli O157 was not isolated at the outbreak site but only implicated from molecular tests. In the Cameroon outbreak, E. coli O157 and Shigella were each isolated in about half of the specimens tested.

Although reported outbreaks of E. coli O157 in Africa have been few to date, available information indicates that the pathogen has wide geographic distribution. Since the 1992 outbreak, culture-proven E. coli O157 diarrheal illness has been reported from multiple locations, including Kenya, Nigeria, Côte d'Ivoire, and Central Africa Republic (22-25). In Egypt, 6 (5%) of 125 meat specimens obtained from slaughterhouses yielded E. coli O157 (26). Because E. coli O157 is not detected by the usual methods used to isolate and identify traditional enteric bacterial pathogens and microbiology laboratories in many countries in Africa do not routinely test for this pathogen, E. coli O157 infections may go unrecognized (27,28). Reports on African dysentery outbreaks attributed to Shigella sometimes indicate that specimens were not tested until several months into the outbreak or do not describe laboratory methods that are suitable for detecting E. coli O157 (29,30). This is unfortunate because the spectrum of clinical illness resulting from Shigella infection overlaps considerably with that of E. coli O157 and mixed outbreaks have been reported (20).

WHO has stated that Shigella dysenteriae type 1 "is the only cause of large-scale, regional outbreaks of dysentery" (emphasis WHO), but data presented here suggest that this assertion may be too restrictive (27). We are concerned that if another large outbreak of severe bloody diarrhea caused by E. coli O157 occurred today in Africa, it might be assumed to be due to Shigella spp. and E. coli O157 would not be sought.

Determining the extent to which E. coli O157 is responsible for dysentery in Africa is of more than academic concern because syndromic management protocols for dysentery in areas where the etiologic agent cannot be readily confirmed often include empiric treatment with antibiotics. Antibiotics have not been clearly shown to ameliorate E. coli O157 infection, and recent data indicate that treating these infections with antibiotics may predispose the patient to developing serious complications, including hemolytic uremic syndrome (HUS) (10,31). HUS is estimated to occur in 8% of children and an unknown proportion of adults with E. coli O157 and, without dialysis, can be fatal (10).

More work is needed to better define the incidence of E. coli O157-associated dysentery in Africa so that optimal recommendations for empiric antibiotic therapy can be provided. At present, we recommend that in outbreaks of dysentery in Africa, stools from ill patients be tested for E. coli O157 in addition to Shigella spp. If the etiologic agent is not identified, consideration should be given to examining stools for other Shiga toxin-producing E. coli. Regional studies of E. coli O157 carriage rates among livestock in various parts of Africa might also be useful in assessing the potential for future outbreaks.

In this investigation, E. coli O157 was recovered from multiple water sources, including a borehole, a standpipe, and water stored in the home. Thus, ensuring the purity of potable water through practical, low-cost strategies might have reduced the risk for infection (32-34).

Several limitations of this investigation should be noted. First, the survey at the plantation did not adjust the period of exposure inquired about to account for differences in date of illness onset for each patient. Instead we asked all persons, both ill and well, about exposures during the 2 weeks preceding the outbreak.

Second, with conditional logistic regression analyses we were unable to identify significant independent predictors of illness among the risk exposures reported by the plantation residents. Many household clusters had at least one indeterminate response to an exposure question (e.g., replied, "Don't remember" or no response) and therefore the entire cluster had to be excluded from such analyses, resulting in conditional regression models that were unstable.

A third limitation is our inability to assess the impact of the E. coli O157 outbreak on human deaths. While visiting area hospitals, we heard anecdotal accounts of patients who became edematous and died without known cause. We suspect that these cases represented end-stage manifestations of HUS, but quantifiable data were not available.

Despite widespread recognition of the importance of environmental factors in facilitating the emergence of infectious agents, the information available in the scientific literature remains relatively limited (35-38). This manuscript combines environmental and veterinary data together with disease incidence, environmental testing, and microbial "fingerprinting" to develop one of the more complete examples currently available. The data presented suggest that carriage of E. coli O157 by cattle, cattle deaths secondary to drought, and heavy rains that resulted in contamination of surface water were important factors contributing to the emergence of E. coli O157 in Africa. Given that drought and heavy rains will likely recur in Africa, the possibility that E. coli O157 will once again emerge to cause a major regional outbreak cannot be excluded. Clinicians need to be aware of this so that delayed diagnosis and inappropriate treatment resulting in loss of lives can be avoided.