Nonetheless, another multistate, multicluster outbreak of cyclosporiasis linked to Guatemalan raspberries occurred in the spring of 1997 (4-6). The Centers for Disease Control and Prevention (CDC) learned of this outbreak in early May, when several health departments reported clusters of cases of cyclosporiasis associated with events (such as banquets) held in April. The outbreak, which is described here, ended shortly after the Guatemalan government and the Guatemalan Berry Commission voluntarily suspended exports of fresh raspberries to the United States. No shipments occurred from 29 May through 14 August (4).

The occurrence of raspberry-associated outbreaks of cyclosporiasis in consecutive years, as well as other outbreaks of cyclosporiasis in 1997 that were linked to mesclun lettuce and basil that did not come from Guatemala (4, 7), highlights the need for improved understanding of the biology and epidemiology of Cyclospora cayetanensis. Although much has been learned in recent years about this coccidian parasite (8-10), unresolved issues that are relevant to foodborne outbreaks include whether animal reservoirs of infection exist (11-18); the maximum rate at which excreted, noninfectious oocysts can sporulate (that is, develop two internal sporocysts, each with two internal sporozoites) and become infectious; the effects of environmental conditions on the rate of sporulation; the median infective dose of oocysts; the factors that make cyclosporiasis seasonal and influence whether infection is symptomatic (for example, causing protracted, relapsing gastroenteritis) (8, 19-21); and the therapeutic alternatives to trimethoprim-sulfamethoxazole (22) for persons intolerant toward sulfa drugs.

Methods

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Epidemiologic Investigation

A cluster of cases of cyclosporiasis was defined as two or more cases occurring among persons who 1) ate at an event during the period from 1 April through 15 June 1997, 2) developed at least one gastrointestinal symptom [such as loose stools] 12 hours to 14 days after the event, and 3) were not known to be associated with the outbreaks linked to mesclun lettuce (in March and early April in Florida [4]) or basil (from mid-June through mid-July in the metropolitan area including northern Virginia, the District of Columbia, and Baltimore [7]). At least one case per cluster had to be confirmed by laboratory testing (for example, with modified acid-fast or hot safranin staining, examination of wet mounts, or demonstration of autofluorescence or oocyst sporulation) (8-10, 23-25). Clinical case definitions for probable cases varied among clusters (Table 1). Health departments conducted retrospective cohort studies by using structured questionnaires about symptoms and event-related exposures.

Case-patients with sporadic cases had laboratory-confirmed cyclosporiasis, developed gastrointestinal symptoms from 1 March through 31 August, were not included in clusters or known to be associated with other outbreaks, and had not traveled outside of the United States or Canada during the 2 weeks before they became ill. The cases of persons who became ill during the period from 1 April through 15 June were defined as having occurred during the period of this outbreak.

Traceback Investigation

To identify sources of the implicated berries, case-patients and investigators identified establishments where the berries were bought or eaten and the dates of purchase or consumption. These establishments identified suppliers (such as distributors) and delivery dates, and suppliers provided shipping documents. A branch of a traceback corresponding to a particular supplier was considered well documented if each step from the consumers back to the country or state of origin was confirmed verbally and in writing (for example, by invoices). An entire traceback was considered well documented if all branches of the traceback were well documented. For Guatemalan berries, airway bill and invoice numbers were used to identify farms that contributed to shipments. The initials previously used to designate Guatemalan exporters (that is, A-G [1]) are used here. The U.S. Department of Agriculture's Agricultural Marketing Service supplied weekly data for sources and amounts of domestic and imported raspberries shipped in the United States.

Statistical Analysis

We used Epi-Info, version 6.04a (CDC, Atlanta, Georgia), for analyses. Univariate relative risks were calculated for exposure variables. Two-tailed P values were computed by using the chi-square test or, if appropriate, the Fisher exact test. A P value less than 0.05 was considered to indicate statistical significance. A relative risk was defined as infinite if the attack rate was greater than 0 among exposed persons but was 0 among the unexposed and if no row or column total in the two-by-two table was 0. A relative risk or P value was considered undefined if a row or column total was 0.

Results

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Epidemiologic Investigation

Clusters

Forty-one clusters of cases of cyclosporiasis were reported (Tables 1 and 2) in association with events held during the period from 1 April through 26 May (Figure 1, top). Of the 41 events, 20 (48.8%) occurred in private residences; 16 (39.0%) occurred in restaurants, clubs, hotels, inns, and resorts; and 5 (12.2%) occurred in other locations. An estimated total of 2541 persons attended the 41 events. Information was available for 1572 attendees (61.9%); 848 had event-associated illnesses and 762 (48.5% of interviewees) were classified as case-patients. Of these 762 persons, 192 (25.2%) had laboratory-confirmed cyclosporiasis.

View larger version (26K): [in this window] [in a new window]   Figure 1. Top. Dates of 41 events associated with clusters of cases of cyclosporiasis (n= 762 cases) in the United States and Canada in April and May 1997. For multiday events, the date of the first day of the event is shown. The last shipment of Guatemalan raspberries in the spring of 1997 was on 28 May. Bottom. Dates of symptom onset for laboratory-confirmed sporadic cases of cyclosporiasis in the United States and Canada in 1997. The white bars represent 31 case-patients who became ill during the period from March through August but not during the outbreak period of April through 15 June. The black bars represent 250 case-patients whose cases were classified as having occurred during the outbreak period. The median date of symptom onset for the 250 case-patients was 26 May (range, 6 April to 15 June). Only 22 persons (8.8%) became ill in April, and most (225 [90.0%]) became ill by 4 June. The date selected as the last date of the outbreak period was 15 June because Guatemalan raspberries exported in late May could still have been available for consumption in early June and because infected persons would have become symptomatic an average of 1 week after exposure. Not all of the sporadic cases of cyclosporiasis were necessarily due to consumption of raspberries.

The incubation periods for the cases ranged from 1 to 14 days (by definition, the incubation period was <15 days); two cases with incubation periods of 1 day and one case with an incubation period of 2 days were laboratory confirmed. The median of the event-specific median incubation periods was 7 days (based on 38 events with available data). The median interval from symptom onset (the date associated with the event's median incubation period) to notification of public health personnel of event-associated illness was 17 days (range, 5 to 59 days; based on 37 events).

The index cases of clusters were brought to the attention of public health authorities in various ways. Index cases for at least 19 clusters (46.3%) were reported by laboratories. Ten of these 19 cases were reported because the laboratory was in a FoodNet site (26) and thus had enhanced laboratory surveillance for various emerging gastrointestinal pathogens (5 cases), cases of cyclosporiasis were officially reportable in the locale (3 cases), or both (2 cases). At least 6 clusters (14.6% of 41) were reported by an event attendee who learned of cyclosporiasis through the media, the Internet, or a medical journal.

Fresh raspberries were the only food common to all 41 events (at 1 of these events, they "quite possibly" were served). For 28 (71.8%) of 39 events, the raspberries had reportedly been rinsed in water. Estimates of the numbers of raspberries per serving were available for 4 events; these estimates were 1, 4, 5, and 12 raspberries. At 16 events (39.0%), raspberries were the only type of berry served (9 events [22.0% of 41]) or were served separately from other berries (7 events [17.1%]). Fresh strawberries, blackberries, and blueberries were served at no more than 30 (73.2%), 22 (53.7%), and 20 (48.8%) events, respectively. At some events, mesclun lettuce (7 events), fresh basil (3 events), or both (2 events) probably were served; none of these events occurred in states known to have had outbreaks linked to these foods (4, 7).

Consumption of raspberries was strongly associated with cyclosporiasis. For the 37 events for which information was available about more than 10% of attendees, the median event-specific attack rate, regardless of exposures, was 66.3% (range, 13.0% to 100%). The median attack rate was higher (91.7% [range, 32.5% to 100%]) among persons who ate items that contained raspberries, with or without other types of berries. Event-specific relative risks for the associations between raspberry-containing items and cyclosporiasis were elevated (>3.0 for 9 events [24.3% of 37 events]; median, 6.8 [range, 3.5 to 10.1]), infinite (16 events [43.2%]), or undefined (11 events [29.7%]) for all but 1 event (relative risk, 1.1). P values for the associations between raspberry-containing items and cyclosporiasis were undefined for 11 events (29.7%) and statistically significant for 15 events (40.5%), including 11 events for which the P value was 0.001 or less.

The possibility that consumption of blackberries caused illness was raised for a cluster of cases associated with a brunch in Ontario at which various types of berries were served separately. All seven identified case-patients recalled eating blackberries, whereas only two of the six who could remember recalled eating raspberries. However, because only 20 (10%) of the approximately 200 attendees were interviewed, statistics for exposure variables are not included here.

Case-Patients with Sporadic Cases

Of the 281 laboratory-confirmed sporadic cases of cyclosporiasis in persons who became ill during the period of March through August, 250 were classified as having occurred during the outbreak period (that is, illness developed during the period from April through 15 June) (Figure 1, bottom; Table 1). The proportions of the 250 case-patients who reportedly ate particular fresh produce items during the 2-week period before they became ill are as follows: for raspberries, 75.9% (161 of 212 patients) compared with 21.1% (4 of 19 patients) for case-patients outside of the outbreak period (P < 0.001; similar comparisons for the following produce were not statistically significant); for strawberries, 70.8% (97 of 137 patients); for mesclun lettuce, 39.8% (33 of 83 patients); for blueberries, 33.9% (41 of 121 patients); for blackberries, 27.8% (49 of 176 patients); and for basil, 21.0% (17 of 81 patients).

Descriptive Case Data

Overall, including both cluster-associated cases (n = 762) and sporadic cases that occurred during the outbreak period (n = 250), 1012 cases of cyclosporiasis were reported in 17 states, the District of Columbia, and 2 Canadian provinces (Table 1). Only 15 (1.7%) of the 890 case-patients with known age were younger than 18 years of age. Two case-patients (both had sporadic cases) were known to be HIV positive, and 8 others (6 had cluster-associated cases and 2 had sporadic cases) were known to have been hospitalized. No deaths were reported. The CDC demonstrated oocyst sporulation in stool specimens from 6 case-patients from 3 states; this supported the conclusion that the organism was Cyclospora cayetanensis.

Traceback Investigation

Raspberries

Because consumption of raspberries at the identified events was strongly associated with cyclosporiasis, we traced the sources of the raspberries served at these events. We obtained well-documented traceback data for 33 (80.5%) of the 41 events (Tables 1 and 3; Figure 2). Even if data for an event were well documented, we often had some uncertainty about which of several shipments of raspberries that could have been used was actually used to supply the raspberries that were served. Therefore, our goals were to identify the possible sources of raspberries for each event (for each step from consumers back to farms) and the common themes among tracebacks for the various events.

View larger version (49K): [in this window] [in a new window]   Figure 2. Tracebacks of sources of raspberries served at events associated with clusters of cases of cyclosporiasis in North America in 1997. *Includes three events (one traced to Guatemalan exporter A and two traced to Guatemalan exporter B) for which there might have been additional branches of the tracebacks without well-documented data; only well-documented data are included here. A farm was considered linked to an event if it contributed to a shipment of raspberries that could have been used at that event.

For 31 (93.9%) of the 33 events with well-documented data, the raspberries either definitely came from Guatemala (8 events [25.8% of 31]) or could have come from Guatemala (that is, 1 of the shipments that could have been used came from Guatemala) (23 events [74.2%]) (Table 3, Figure 2). For these 31 events, which occurred from 1 April through 26 May, the universe of shipments from Guatemala that could have supplied the berries included 59 shipments from 26 March through 22 May, a period when most raspberries shipped in the United States were not from Guatemala (Figure 3). Each of 16 of these 59 shipments was common to tracebacks for 2 to 5 events in up to three states, and the tracebacks were identical (that is, the distributors and shipments were the same) for 2 events in one state and for 2 events in another state.

View larger version (26K): [in this window] [in a new window]   Figure 3. Sources and amounts of fresh raspberries (domestic and imported) shipped within the United States by week for 9 weeks in April and May 1996 (left) and 1997 (right). The white bars represent raspberries from California; the striped bars represent raspberries from Chile; the black bars represent raspberries from Guatemala; and the dotted bars represent raspberries from other sources. The dates for weeks 1 through 9 range from 31 March 1996 to 1 June 1996 and from 30 March 1997 to 31 May 1997; the last date in each week is shown under each bar. Data on Chilean raspberries were unavailable for week 1 in 1997. The median proportions of the raspberries per week that were from Guatemala were 13.8% (range, 0% to 21.9%) in 1996 and 11.0% (range, 2.8% to 18.4%) in 1997 (excluding week 1).

The 59 shipments, which contained a median of 452 kg of raspberries (range, 91 to 2130 kg), followed diverse paths. They were sent by eight Guatemalan exporters—four were definite (each was the sole identified exporter for raspberries for 1 event) and four were possible (each was one of multiple possible exporters for 1 event)—to 13 importers (9 definite and 4 possible). They arrived on eight airline carriers (five definite and three possible) at four U.S. ports of entry (three were definite [Miami, Los Angeles, and New York], and one was possible [Houston]). The median interval from shipment to consumption was 7.5 days (range, 5 to 11 days) for the raspberries at the 10 events that were traced to 1 (rather than >1) shipment per event.

Most tracebacks identified multiple possible Guatemalan source farms per event rather than only the definite source farm or farms because most events were traced to multiple possible shipments (median, 2 per event [range, 1 to 9 per event]) and because most shipments included raspberries from multiple farms (median, 3 farms per shipment [range, 1 to 14 farms per shipment]). Overall, various combinations of 50 farms contributed to the 59 shipments (median, 7 possible farms per event [range, 1 to 23 farms per event]). However, for 1 event in 1997 (none in 1996), only 1 farm (farm Y of exporter A) contributed to the 1 shipment from Guatemala. Overall, raspberries from farm Y could have accounted for 21 (67.7%) of the 31 events and for 13 (92.9%) of the 14 events traced solely to exporter A (Figure 2). Although farm Y was not identified as the only possible Guatemalan source farm for any events in the 1996 outbreak, it could have accounted for 18 (62.1%) of the 29 events with well-documented traceback data, including 16 (88.9%) of the 18 events traced solely to exporter A. Overall, the 31 events in 1997 could have been accounted for by farm Y and various combinations of as few as 3 other farms; the 29 events in 1996 could have been accounted for by as few as 6 farms; and both outbreaks could have been accounted for by a total of as few as 7 farms.

In 1997, well-documented tracebacks for 2 events led to only non-Guatemalan sources of raspberries. For 1 of these events, the importer's records indicated that Chilean raspberries were supplied to the produce distribution center. However, during the same period, the importer's stock included Guatemalan raspberries from two farms that were possible source farms for 15 or 16 of the 31 events in the overall investigation. In addition, the raspberries were served mixed with Guatemalan blackberries that could have been from farm Y. For the other event, California was the apparent source of the raspberries. The possibility that raspberries from multiple sources were commingled was raised by an investigator who had observed the distributor's practices.

Blackberries

We traced the sources of blackberries because blackberries were served mixed with raspberries at 16 events and because some Guatemalan farms grow both types of berries. For 13 (81.2%) of the 16 events, we obtained well-documented data about the sources of the blackberries, either for the entire traceback (7 events) or for some, but not all, possible branches of the traceback (6 events). (Well-documented traceback data were not obtained for the blackberries or raspberries that were served [separately] at the brunch in Ontario.) Guatemala was a possible source of the blackberries for 12 (92.3%) of these 13 events, including at least 5 for which it definitely was the source. Farm Y was a possible source farm for 5 of the 11 events for which Guatemalan farm data were available; these 5 events include 4 events for which farm Y could not have been the source of the raspberries that were served. Overall, 17 of the 51 farms or cooperatives that contributed berries to at least one of the possible blackberry shipments also contributed to at least one of the possible raspberry shipments.

Discussion

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The epidemiologic and traceback evidence collected about the 41 clusters of cases of cyclosporiasis described here, which were dispersed across North America in the spring of 1997, implicated fresh Guatemalan raspberries as the vehicle of the outbreak. The following evidence implicated raspberries and then Guatemala as the source of the raspberries. First, raspberries were the only food common to all 41 events associated with clusters of cases. Second, consumption of raspberries was strongly associated with cyclosporiasis. Third, the preponderance of the traceback data implicated Guatemala as the source of the raspberries, even though most of the raspberries shipped in the United States during the outbreak period were not from Guatemala (Figure 3). Fourth, the outbreak ended shortly after exportation of Guatemalan raspberries was suspended, despite the continued availability of raspberries from elsewhere (Figure 3). Finally, similar outbreaks linked to Guatemalan raspberries have occurred in consecutive years. In addition to the multistate outbreaks that occurred in 1996 and 1997, an outbreak of cyclosporiasis in Florida in 1995 might have been caused by imported raspberries and thus might have been a harbinger of the later outbreaks (27). In the spring of 1998, the U.S. Food and Drug Administration did not permit the importation of fresh Guatemalan raspberries into the United States (the importation of blackberries continued unrestricted). Importation into Canada continued, and an outbreak linked to Guatemalan raspberries occurred in Ontario in May 1998 (28).

Table 2 compares selected features of the clusters of cases in the strikingly similar 1996 and 1997 multistate outbreaks. The true magnitudes of these outbreaks are unknown and therefore cannot be compared. The first events associated with identified clusters of cases occurred on 3 May 1996 and 1 April 1997. The relative importance of factors in Guatemala (such as environmental conditions and the exportation of more raspberries in April 1997 than in April 1996 [Figure 3]) and factors in the United States (such as greater awareness of cyclosporiasis and more laboratory expertise in identifying Cyclospora oocysts in 1997) in accounting for the apparently earlier onset of the 1997 outbreak is unknown. Although the 1997 outbreak began in April, the onset of the rainy season in the raspberry-growing regions of Guatemala ranged from early May to early June; this was several weeks later than the onset of the rainy season in 1996. Most (82.9%) of the events associated with clusters in the 1997 outbreak occurred in May. In fact, similar numbers of identified events occurred in May 1996 and May 1997 (36 and 34, respectively).

For the clusters of cases reported in 1997, consumption of raspberries was strongly associated with cyclosporiasis; however, the food-exposure data for the sporadic cases are difficult to interpret because they were not compared with data for controls. Even so, the fact that the number of cluster-associated events and the number of sporadic cases peaked during the same period (Figure 1), which did not substantially overlap with the periods of the outbreaks linked to mesclun lettuce or basil (4, 7), suggests that many sporadic cases were attributable to consumption of raspberries. Some persons with sporadic cases of cyclosporiasis who reportedly did not eat raspberries might have eaten them without realizing or remembering that they had done so, whereas others could have become infected in other ways.

As in 1996, the lack of commonalities in the distribution system (for example, in U.S. ports of entry) of the raspberries implicated in the 1997 outbreak again suggests that the berries were contaminated in Guatemala, probably on farms. However, even well-documented tracebacks generally identified multiple possible source farms per event rather than only the definite source farm or farms. The key finding that for one event, only one farm (farm Y) contributed to the one shipment from Guatemala underscores the importance of conducting tracebacks for as many events as available resources allow, in the hope that additional tracebacks will lead to specific farms of origin or provide other useful information. Except for this association with farm Y, we are uncertain about how many and which of the possible farms accounted for the outbreak. However, the events with well-documented traceback data in the 1997 outbreak could have been accounted for by relatively few farms (farm Y and various combinations of as few as three others), and such events in both 1996 and 1997 could have been accounted for by a total of as few as seven farms.

Although the mode of contamination of the raspberries remains unknown, simultaneous (because no one farm could account for either the entire 1996 outbreak or the entire 1997 outbreak) and persistent (because each outbreak lasted longer than 1 month) contamination on multiple farms that shared a common attribute or practice is the most likely explanation for both outbreaks. After the 1996 outbreak, we hypothesized that raspberries might have been contaminated when sprayed with insecticides, fungicides, and fertilizers that had been mixed with water of variable quality (1). The occurrence of subsequent outbreaks suggests that the control measures instituted after the 1996 outbreak (some of which were intended to improve water quality) were not fully implemented by some farms, were ineffective, or did not address the true source of contamination (4, 28). In anticipation of the 1999 spring export season, the Guatemalan government and the Guatemalan Berry Commission are developing a more comprehensive plan for growing and handling raspberries; this plan is being reviewed by U.S. and Canadian officials (28). Research to explore possible modes of contamination has been constrained by the unreliability of the available testing methods for the detection of low levels of Cyclospora in food and environmental samples (including water samples) and by the limited numbers of samples from Guatemalan farms that have been available for testing. Given the short shelf life of fresh produce and the long incubation period for cyclosporiasis, leftover raspberries from the identified events were unavailable for testing when the clusters of cases were detected.

Our data from the 1996 (1) and 1997 outbreak investigations, as well as data from other investigators (17), indicate that rinsing produce does not reliably remove Cyclospora oocysts. Whether Cyclospora oocysts are susceptible to the doses of irradiation that are permissible for food in the United States is unclear. Of the two coccidian parasites previously studied in this regard, one was susceptible (Toxoplasma gondii [29]) and one was resistant (Eimeria bovis [30]); adequate assays for assessing the viability and infectivity of Cyclospora oocysts are not available. The occurrence of outbreaks of cyclosporiasis linked to various types of fresh produce (1, 4, 7), as well as fresh produce-related outbreaks caused by other etiologic agents (31, 32), highlights the needs for improved surveillance for foodborne illness (33-35) and for stronger prevention and control measures to ensure the safety—from farm to table—of produce eaten raw (2, 34).

Appendix

The Cyclospora Working Group includes the following persons (asterisks denote members of the Epidemic Intelligence Service, Epidemiology Program Office, CDC).

California: Janet C. Mohle-Boetani, MD, James M. Waddell, and Jeffrey A. Farrar, DVM, MPH, PhD (California Department of Health Services); Gwendolyn E. Bell, MA, MPH, Michael P. Tormey, MPH, and Laurene Mascola, MD, MPH (Los Angeles County Department of Health Services); and Amy L. Bellomy, RN, MPH, and Peggy Langle, REHS (Santa Barbara County Health Care Services).

Connecticut: Randall S. Nelson, DVM, MPH (Connecticut Department of Public Health).

District of Columbia: Madeleine Fletcher, PhD, MPH, and Martin E. Levy, MD, MPH (District of Columbia Department of Health).

Florida: Alan D. Rowan, MPA (Florida Department of Health).

Illinois: Carla J. Bush, LEHP, BA, MPA (City of Evanston Health Department).

Maryland: David M. Portesi, MPH (Maryland Department of Health and Mental Hygiene); and Christine Lacey, MSN, RNC (Montgomery County Department of Health and Human Services).

Massachusetts: Daniel M. Hamlin, MS, and Leonard Letendre, DVM (Massachusetts Department of Public Health); and M. Anita Barry, MD, MPH (Boston Public Health Commission).

Nebraska: Carol D. Allensworth, BS, MT(ASCP)SM (Douglas County Health Department); and Thomas J. Safranek, MD (Nebraska Department of Health and Human Services).

Nevada: Debra L. Brus, DVM (Washoe County District Health Department).

New York: Douglas C. Hosterman (Albany County Health Department); John J. Campana, RS (Monroe County Department of Health); Abby J. Greenberg, MD (Nassau County Department of Health); James R. Miller, MD, MPH, Annie Fine, MD*, and Sarah L. Terry (New York City Department of Health); Barbara Wallace, MD*, Michael J. Cambridge, BS, RS, and Norman W. Fogg, MPS, RS (New York State Department of Health); and Germaine Jacquette, MD (Westchester County Department of Health).

Ohio: Ellen P. Salehi, MPH (Ohio Department of Health).

Pennsylvania: Marian L. Nygard, RN (Pennsylvania Department of Health).

Rhode Island: Utpala Bandy, MD, MPH (Rhode Island Department of Health).

Texas: Jeffrey P. Taylor, MPH (Texas Department of Health); and Rose Lee Bell, PhD, MPH (Houston Department of Health and Human Services).

Vermont: Ruth Cameron, BA, RN (Vermont Department of Health).

Canada: Eric Mintz, BSc, MSc, PhD (Regional Municipality of York, Health Services Department); Andrea G. Ellis, DVM, MSc, and Brent Dixon, BSc, PhD (Health Canada); and Charles A. Le Ber, DVM, DVPH (Ontario Ministry of Health).

United States: Vance J. Dietz, MD, MPH&TM, William R. MacKenzie, MD, Susanne P. Wahlquist, MS, Kimberley B.J. Hannak-Donaldson, MS, Henry S. Bishop, Michael J. Arrowood, PhD, Deborah A. Levy, PhD, MPH*, and Lawrence M. Barat, MD, MPH* (Division of Parasitic Diseases, National Center for Infectious Diseases, CDC); Stephanie H. Factor, MD, MPH*, and Cindy R. Friedman, MD* (Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, CDC); Lauren B. Ball, DO, MPH* (National Center for Environmental Health, CDC); Mark L. Messonnier, MS, PhD (Epidemiology Program Office, CDC); and Ellen F. Morrison, BA, William H. Cochran, BS, Oliver D. Cook, MS, MPH, Terry G. Forrest, BS, Mark I. Fow, PhD, Elizabeth A. Keville, BA, Barbara Marcelletti, BA, and Linda Wisniowski, MS (Office of Regulatory Affairs, U.S. Food and Drug Administration).