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    Monthly cases of diarrhea associated with Campylo-bacter, enterotoxigenic E. coli (ETEC), Shigella, rotavirus, and other enteropoathogens among children less than 6 years old brought for treatment to Abu Homos District or Benha Fever Hospital, Arab Republic of Egypt, May 2000 to May 2002.

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CLINIC-BASED SURVEILLANCE FOR BACTERIAL- AND ROTAVIRUS-ASSOCIATED DIARRHEA IN EGYPTIAN CHILDREN

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  • 1 U.S. Naval Medical Research Unit No. 3, Cairo, Arab Republic of Egypt; U.S. Naval Medical Research Unit No. 2, Jakarta, Indonesia; Ministry of Health and Population, Arab Republic of Egypt

To identify enteropathogens for vaccine development, we implemented clinic-based surveillance for severe pediatric diarrhea in Egypt’s Nile River Delta. Over 2 years, a physician clinically evaluated and obtained stool samples for microbiology from patients with diarrhea and less than 6 years of age. In the first (N = 714) and second clinic (N = 561), respectively, 36% (N = 254) and 46% (N = 260) of children were infected with rotavirus, enterotoxigenic Escherichia coli (ETEC), Campylobacter, or Shigella. When excluding mixed rotavirus-bacterial infections, for the first and second clinic, 23% and 10% had rotavirus-associated diarrhea, and 14% and 17% had ETEC-associated diarrhea, respectively. Campylobacter-associated diarrhea was 1% and 3%, and Shigella-associated diarrhea was 2% and 1%, respectively, for the two clinics. Rotavirus-associated diarrhea peaked in late summer to early winter, while bacterial agents were prevalent during summer. Rotavirus-associated cases presented with dehydration, vomiting, and were often hospitalized. Children with Shigella- or Campylobacter-associated diarrhea reported as watery diarrhea and rarely dysentery. ETEC did not have any clinically distinct characteristics. For vaccine development and/or deployment, our study suggests that rotavirus is of principle concern, followed by ETEC, Shigella, and Campylobacter.

INTRODUCTION

With the widespread use oral rehydration therapy strategies, diarrheal disease deaths have declined substantially in the developing world.1,2 Diarrhea morbidity has not had a concomitant decrease, with one report estimating 3 to 5 billion diarrhea cases occurring worldwide each year, mostly among children.1,3 Clearly, more needs to be done to reduce diarrheal diseases including deployment of enteric vaccines.

Since 1992, we have performed several longitudinal, village-based studies using active case detection to examine the epidemiology of pediatric diarrhea in Egyptian children.49 As in other developing countries, these projects demonstrate that diarrheal diseases continue to be a major disease burden. All-cause diarrhea was 2.9 and 5.5 episodes per child-year of follow-up among children less than 3 years of age in Abees and Abu Homos, respectively.4,6,8 Enterotoxigenic Escherichia coli (ETEC) was commonly isolated with 0.6 episodes and 1.5 episodes per child-year for the same two areas, respectively.4,8 Besides ETEC, Campylobacter, rotavirus, and Shigella have been isolated in 0.6, 0.24, and 0.2 episodes per child-year.5,8,9 For these enteropathogens, dehydration varied from a low of 12% for ETEC-associated to a high of 56% for rotavirus-associated diarrhea.

To complement these studies, starting in May 2000 we developed and implemented passive surveillance at two Egyptian hospitals located in the Nile River Delta. The study was completed in May 2002. The primary objective of this study was to assess the epidemiology and clinical characteristics of severe diarrhea, diarrhea severe enough to bring a child to medical attention. We expect that these results will be useful for decision analysis models for prioritizing vaccine requirements.

MATERIALS AND METHODS

Study sites.

Surveillance was conducted at the outpatient pediatric clinic of Benha Fever Hospital and the Abu Homos District Hospital. Both medical facilities are government referral hospitals in which services are free or require minimal payment. Benha, located north of Cairo is a periurban community of 455,000 persons, where 13% are less than 6 years of age and 29% are illiterate. In urban areas of Benha, nearly 90% of households and in rural areas, 10% of households have water and sewage disposal provided by the municipality. Abu Homos is an agricultural community of 348,000 persons, located southeast of Alexandria, Egypt, where 17% are less than 6 years of age and 56% of the population is illiterate. In Abu Homos, approximately 90% of urban households have municipal water and sewage disposal as compared with 55% of rural residents receiving municipal water and none have sewage disposal (statistics from the Egyptian Ministry of Health and Population).

Enrollment.

It was common during the summer months for more than 20 children a day to be evaluated for diarrhea. To maintain quality data collection, a prestudy decision was made to sequentially register and enroll only every fifth child. If a guardian did not want to participate, the caretaker of the next registered child was asked to enroll their child.

Data collection.

After informed consent, a clinical history and physical examination was recorded on a structured, pre-tested questionnaire.

Specimen collection, handling, and storage.

Two rectal swabs and a stool sample were obtained from each study child. One swab was placed into a tube of Cary-Blair (CB) transport medium and the other into a tube containing buffered-glycerol-saline (BGS) enrichment medium. After collection, the inoculated tubes were refrigerated at 2°C to 8°C while the stool sample was split into seven aliquots and then frozen at −20°C. Within 3 days of collection, specimens were sent to U.S. Naval Medical Research Unit No. 3 (NAMRU3) located approximately 3 hours by car from the study clinics. During transportation, rectal swabs were placed in a cold box with ice packs while frozen specimens were placed in a container with dry ice. Upon arrival at NAMRU3, all specimens were accessioned and rectal swabs were sent to the microbiology laboratory for culture, and the frozen samples were transferred to a −70°C freezer.

Microbiology.

Using conventional microbiologic techniques, both rectal swabs were streaked onto standard laboratory agar media for the recovery and identification of common enteric bacterial pathogens: Shigella, Salmonella, Campylobacter, and Vibrio.1013 Campylobacter isolates were further speciated using hippurate hydrolysis,14 and Shigella isolates were serogrouped and serotyped by slide agglutination using commercial antisera (Difco Laboratories, Livonia, MI).15 In addition, five E. coli–like colonies were picked and tested for the expression of heat-labile enterotoxin (LT) and/or heat-stable enterotoxin (ST) using a GM1 ELISA.16,17 Colonies testing positive for LT or ST were further tested for expression of colonization factor (CF) antigens CFA/I, CFA/II (coli surface antigen [CS] 1, CS2, CS3), CFA/III, CFA/IV (CS4, CS5, CS6), CS7, CS17, PCFO159, and PCFO166 by monoclonal antibody dot blot assay.18 Following the manufacturer’s instructions, a commercial enzyme immunoassay (Premier Rotaclone, Meridian Bioscience, Inc., Cincinnati, OH) was used to identify rotavirus antigen from the submitted stool samples.

Definitions.

Time from disease onset until evaluation was termed “illness length.” Stooling patterns were described by the “mean number of stools” in the 24 hours before evaluation and “mean maximal stools” on any day since the illness began. Dehydration was defined according to definitions of the World Health Organization.19 An episode lasting less than 14 days without visible blood was termed “acute watery diarrhea,” while “dysentery” was defined as an illness lasting less than 14 days with visible blood or mucus in the stool. “Persistent diarrhea” was defined as an episode with or without blood lasting longer than 14 days. “Fever” was defined as a rectal temperature > 38.5°C and “severe fever” as rectal temperature > 40.0°C. When parents reported a history of fever, the fevers were classified as present or absent. Seizures were defined as a sudden, violent, involuntary contraction of a muscle group. Summer months were from May to October and cool months were from November to April. If an organism was identified from the stool sample, the child was classified as “infected” with that organism. If a single pathogen was isolated from the stool, then the episode was referred to as “pathogen”-associated diarrhea (e.g., ETEC-associated diarrhea). “Undiagnosed diarrhea” included any episode in which a studied bacterial pathogen or rotavirus was undetected.

Analysis.

We used a χ2 test of independence to determine if there was a statistically significant difference in the proportion of children with a clinical characteristic such as vomiting among enteropathogens (i.e., Campylobacter, ETEC, Shigella, rotavirus, or undiagnosed agents). If a statistically significant difference was detected among the enteropathogens, then a series of χ2 tests were used to determine which pair (e.g., ETEC versus rotavirus) of enteropathogens differed by that clinical characteristic. When the symptom was measured on a continuous scale (e.g., mean number of stools in 24 hours), the normality of the distribution was tested using Shapiro-Wilk test,20 and analysis of variance (ANOVA) was used to determine if there were statistically significant differences in the mean of that variable when categorized by enteropathogen. When a statistically significant difference was detected, Student’s t tests were used to identify which pair of means was statistically different. To determine if a pathogen showed seasonality, we tested if the proportion of summer cases (May–October) was statistically greater than 50% of all cases using a single sample binomial test of significance.21

All data was double entered into Epi-info version 6. Stat-exact 4.0 (Cytel Software Corporation, Cambridge, MA); SAS 6.12 and SAS 9.0 (SAS, Cary, NC) were used for all analyses. Statistical significance was two-tailed and set at P < 0.05 for all analyses.

This study was approved by the Institutional Review Board of the U.S. Naval Medical Research Unit No. 3, Arab Republic of Egypt and the Ministry of Health and Population, Arab Republic of Egypt. The work was performed under work unit 6000.RAD1.D.0301. Written informed consent was obtained from each parent during enrollment.

RESULTS

Patient accrual.

Between May 2000 and May 2002, 561 children in Benha and 714 children in Abu Homos (N = 1,275) were enrolled. Of the parents initially approached, 96% (N = 1,221) agreed to have their child enrolled with the other 4% being replaced by the next eligible child. Of the 1,275 children, 37 (3%) of these children made a second visit for the same episode (i.e., a visit made within 14 days of the first visit). None of these children were enrolled at the follow-up visit.

Rectal swabs were collected from 99% of children in Benha and 100% of children in Abu Homos. A stool sample was obtained from 90% (N = 505) of the children from Benha and 73% (N = 521) of the children from Abu Homos. The greater frequency of stool collection in Benha appeared to be due to a greater willingness on the part of Benha parents to wait until there children produced a stool.

Disease burden.

Because one in five children were enrolled, we extrapolated that 2,805 clinic visits to Benha Clinic and 3,570 clinic visits to Abu Homos for treatment of diarrhea were made during the study. Based on hospital records, this represented 12% and 19% of all clinic visits for children under 6 years of age at Benha and Abu Homos Clinics, respectively.

Diarrhea cases.

The number of children with diarrhea at these clinics was inversely correlated with age (Table 1). Children less than 12 months were 56% and those from birth to 24 months were 87% of the population. This distribution of cases was similar to that of Benha (P = 0.5). Female children were somewhat less likely to be brought for treatment at both clinics.

Etiologies.

For Benha Fever and Abu Homos District Clinic, 46% (N = 260) and 36% (N = 254) of children, respectively, were infected with Campylobacter, Shigella, ETEC, rotavirus, or mixed bacterial-rotavirus infections (Table 1). The distribution of these enteropathogens differed by study site (P < 0.0001) due to differences in the isolation rate of Campylobacter (P = 0.03), rotavirus (P < 0.0001), mixed infections (P = 0.02), and undiagnosed diarrhea cases (P = 0.0001).

The distribution of diarrhea episodes stratified by age and enteropathogen showed a distinct pattern. Except for ETEC cases in Abu Homos, the number of episodes seeking treatment increased from birth to 5 months old, peaked at 6 to 11 months old, and decreased over the next two successive age categories (i.e., 12 to 23 and 24 to 59 months). Two-hundred sixty diarrhea cases associated with rotavirus (161 Benha, 99 Abu Homos) were detected. Of these 260 cases, rotavirus was the sole pathogen in 204 (78%) cases. Of the 258 ETEC-associated episodes (111 Benha, 148 Abu Homos), ETEC was the sole pathogen isolated from the stool in 201 cases. ETEC more frequently produced LT (N = 115, 45%) followed by ST (N = 100, 39%). The remaining ETEC isolates produced LTST (case = 21, 8%) or mixed enterotoxin types such as LT and LTST (N = 22, 8%).

An ETEC colonization factor was identified in 127 (49%) of the ETEC isolates. However, CF expression varied by enterotoxin expression. CFs were less frequently identified among ETEC strains expressing LT (21%, N = 24) than in strains expressing ST (70%, N = 70), LTST (71%, N = 15), or mixed strains (82%, N = 18). CFs were heterogeneous. CFA/I (N = 45), CFA/IV (N = 33), and CS7 (N = 15) were the three most common adhesins, followed by CFA/II (N = 12), PCFO166 (N = 10), CFA/III (N = 4), PCFO159 (N = 2), CS17 (N = 3), and two mixed CFs (CS6 and CFA/II; CS7 and CFA/I).

Campylobacter was isolated from 38 stools (9 Benha, 29 Abu Homos) and was the sole pathogen in 26 (68%) cases. Ninety-five percent of isolates were C. jejuni. Shigella was isolated from 23 children (9 Benha, 14 Abu Homos) and was the sole pathogen in 19 (73%) cases. Of the 23 isolates, 19 (83%) were S. flexneri, three (13%) were S. dysenteriae, and one (4%) was S. sonnei.

Diarrhea seasonality.

Children were more likely to be brought for treatment during the warm through early cool season in Abu Homos (Figure 1). ETEC was the prominent organism during the warm season. In Benha, diarrhea was more common during the warm season of the first year but showed no increase during the warm season of the second year. For both years in both clinics, but especially, the first year in Benha, there was a noticeable increase in cases during the late summer, early cool season primarily due to rotavirus-associated diarrhea. The increase in rotavirus isolation during the first year contributed to the higher proportion of rotavirus-associated cases in Benha (23%) than Abu Homos (10%). Although occurring mainly during the warmer months, Campylobacter and Shigella occurred sporadically at other times of the year.

The seasonality of ETEC differed by enterotoxin production. ST production was greater in the summer months for both sites (88%, N = 46, P < 0.0001 in Abu Homos; 85%, N = 23, P = 0.0003 in Benha). LT production did not differ by season (65%, P = 0.05 in Abu Homos and 57%, P = 0.5 in Benha). Of ETEC-associated episodes, 87% (N = 111, p = < 0.0001) of ETEC cases associated with a CFA occurred during the warm season, while 60% (N = 78, P = 0.04) of those not expressing a CF occurred during the summer months. The proportion of summer cases was much greater for episodes that expressed a CF than for those ETEC cases that did not express an adhesin (P < 0.0001).

Clinical characteristic.

Children were brought for treatment within 3 to 5 days of disease onset, but children who had rotavirus-associated diarrhea were taken for health care 1 day earlier than children with undiagnosed diarrhea (P = 0.003) (Table 2). Loose motions in the 24 hours before treatment differed by enteropathogen with the frequency of stooling for Shigella-infected children being statistically greater for them than for children with ETEC (P = 0.03), Campylobacter (P = 0.04), and undiagnosed diarrhea (P = 0.02), but statistically similar to that of children with rotavirus (P = 0.8).

Reports of bloody and/or mucoid stools were similar for Shigella and Campylobacter but differed for other enteropathogens. Of Shigella-associated infections, 11% (N = 2) were observed by parents to have some blood and 11% (N = 2) were observed to have much blood in their stools. The proportion of children with some and much blood was statistically greater for Shigella than for rotavirus (P < 0.0001), ETEC (P = 0.0003), or undiagnosed diarrhea cases (P = 0.002) but not for Campylobacter (P = 0.58).

Mucoid stools were more frequent when patients were infected with Campylobacter than with rotavirus (P = 0.0006), ETEC (P = 0.03), and Shigella (P = 0.04) but not against undiagnosed diarrhea cases (P = 0.7). At the time of medical evaluation, 17% (N = 209) children had a documented fever with 1% having a temperature ≥40°C. Neither the historical (P = 0.1) nor objective (P = 0.7) cases of fever were more frequently associated with any specific enteropathogen. Vomiting was statistically more common among children with rotavirus-associated diarrhea than for children infected with ETEC (P < 0.0001), Campylobacter (P < 0.002), Shigella (P < 0.04), and undiagnosed diarrhea (P < 0.0001).

Children infected with Shigella reported four (22%) seizures, and the frequency of seizures was greater for Shigella than ETEC (P = < 0.0001), rotavirus (P = < 0.0001), and undiagnosed diarrhea (P = < 0.0001). Only children with Campylobacter-associated diarrhea had rates of seizures similar to that of Shigella-associated diarrhea (P = 0.2).

Rotavirus-associated diarrhea was linked to a significant number of dehydrated children at the time of evaluation. Rotavirus cases presented with 39% “some” and 3% “severe” dehydration. Rotavirus-associated dehydration was statistically greater than for children infected with ETEC (P = 0.0003), Campylobacter (P = 0.03), and undiagnosed diarrhea cases (P = 0.0001) but not statistically for Shigella (P = 0.72).

The infecting enteropathogen also affected the rates of hospitalization in children with diarrhea. Likely related to the increased frequency of dehydration, children with rotavirus-associated diarrhea were more likely to be hospitalized and showed a statistically significant difference compared with ETEC (P = 0.0005), Campylobacter (P = 0.01), and undiagnosed diarrheal cases (P = 0.0001), but statistically similar to that of Shigella (P = 0.27).

DISCUSSION

The current study investigated the epidemiologic and clinical features of selected enteropathogens among children with diarrhea severe enough to require evaluation and bridges our understanding of diarrhea gathered from field-based, active surveillance.46,8,22 In Benha, 1 in 10, and Abu Homos, nearly 1 in 5, pediatric visits were for diarrhea, and for both sites nearly one-third of children with diarrhea were hospitalized.

Similar to our community-based studies, ETEC was the predominant bacterial pathogen recovered. As expected, ETEC episodes were more severe in the current study than ETEC episodes identified in community studies.4,8,23 Like the community-based studies, no clinical feature allowed ETEC to be differentiated from other diarrheal etiologies.4

Consistent with our community-based studies, ST-ETEC was more commonly isolated in the warmer months, while LT-ETEC showed no seasonal variation.4,8 ETEC expressing a CF were also more common in the warmer months likely due to the higher proportion of ST-ETEC strains that express a CF.8

In agreement with other studies of pediatric diarrhea, we found rotavirus to be common with rates equal to those of ETEC. This is in contrast to our field-based study where rotavirus was the fourth leading cause of diarrhea after ETEC-, Campylobacter-, and Shigella-associated diarrhea.5 This highlights that while rotavirus may induce fewer episodes than other enteropathogens, it appears to induce a greater proportion of severe cases. Also in the current study, rotavirus occurred more often during the cooler months, a pattern similar to that in other temperate climates24,25 and similar to a report made from Bilbeis, Egypt.23 These data contrast with results from our community-based study that identified rotavirus more often in the warmer months.5 Taken together, these studies may suggest that rotavirus is a disease of late warm and early cool season but seasonality may vary year-to-year.

For rotavirus, certain clinical features were suggestive of the infection. A rapid onset of symptoms, frequent watery stools, recurrent vomiting, dehydration, and hospitalization occurred more commonly with rotavirus than the other enteric pathogens.

Campylobacter- and Shigella-associated diarrhea were identified less frequently than ETEC- or rotavirus-associated cases. Campylobacter- and Shigella-associated cases were occasionally associated with blood and/or mucus in stools as reported elsewhere in Egypt,8,26 while Campylobacter infections were also found to be associated with convulsions, possible febrile seizures, that have also been reported elsewhere.27,28

A potential limitation to the current study is the generalizability of the data from two clinics of the Nile River Delta to the pediatric population of Egypt. An additional concern is that differences between the two study sites may have been due to dissimilarity in interviewing, clinical methods, or sample collection. In an attempt to minimize this bias, we structured and standardized all our data collection procedures and then provided the same training and supervision to investigators and staff at both facilities. As rotavirus testing can only be performed on stool sample, the lower percentage of stool samples available from Abu Homos may partially explain why rotavirus was less commonly identified at that site. To check for this possibility, an analysis was performed that was limited to children from whom a stool sample was available for rotavirus testing and the difference in rotavirus isolation rates remained.

Study implications.

Observations from this investigation may be important for inclusion in data analysis models for prioritization of control strategies, including the development and deployment of new enteric vaccines. These results are similar to those of other developing countries where watery diarrhea is common and dysentery infrequent. The data suggest that interventions should concentrate on children less than 2 years of age, where disease is most common. Among these children, rotavirus-associated diarrhea was the most prevalent and severe. Although laboratory confirmation of rotavirus would be preferable, even in the absence of laboratory confirmation, it would be desirable for medical staff to initiate surveillance for rotavirus-like symptoms (i.e., vomiting and severe diarrhea).

Table 1

Distribution of diarrhea episodes associated with bacterial agents and rotavirus by age and gender among Egyptian children less than 60 months old brought for treatment to Abu Homos District Hospital or Benha Fever Hospital, 20 May 2000 to 19 May 2002

VariableCampylobacter (n = 20, 3%)‡ETEC* (n = 123, 17%)Shigella (n = 8, 1%)Rotavirus (n = 74, 10%)Mixed† (n = 29, 4%)Undiagnosed (n = 460, 64%)Total (n = 714, 100%)
* Enterotoxigenic E. coli.
† Mixed bacterial-rotavirus cases include 5 rotavirus plus Campylobacter, 20 rotavirus plus ETEC, 4 ETEC plus Campylobacter for Abu Homos; 2 rotavirus plus Campylobacter, 29 rotavirus plus ETEC, 3 Shigella plus ETEC, and 1 Campylobacter plus ETEC.
‡ Total cases, row percent.
§ Total cases, column percent.
Age in months
    0 to 56 (30)§21 (17)1 (13)9 (12)6 (21)94 (20)137 (19)
    6 to 129 (45)33 (27)5 (62)36 (49)12 (41)166 (36)261 (36)
    12 to 233 (15)44 (36)0 (00)21 (28)10 (34)118 (26)196 (27)
    24 to 592 (10)25 (20)2 (25)8 (11)1 (03)82 (18)120 (17)
    Male13 (65)64 (52)3 (38)39 (53)18 (62)251 (55)388 (54)
Benha Fever Hospital
(n = 6, 1%)(n = 78, 14%)(n = 11, 2%)(n = 130, 23%)(n = 35, 6%)(n = 301, 54%)(n = 561, 100%)
Age in months
    0 to 50 (0)8 (10)1 (9)19 (15)5 (14)47 (16)80 (14)
    6 to 125 (83)29 (37)5 (45)61 (47)18 (51)117 (39)235 (42)
    12 to 231 (17)23 (29)3 (27)41 (32)10 (29)75 (25)153 (27)
    24 to 590 (00)18 (23)2 (18)9 (07)2 (06)62 (21)93 (17)
    Male3 (50)34 (44)6 (55)77 (59)20 (57)175 (58)315 (56)
Table 2

Clinical characteristics of diarrhea in Egyptian children less than 60 months old seeking treatment at Abu Homos District Hospital and Benha Fever Hospital, 20 May 2000 to 19 May 2002

CharacteristicsCampylobacter (n = 26)ETEC* (n = 201)Shigella (n = 19)Rotavirus (n = 204)Undiagnosed† (n = 761)Total (n = 1,211)‡P value§
* ETEC, enterotoxigenic E. coli.
† Undiagnosed diarrhea are episodes not associated with studied bacterial agents or rotavirus.
‡ 1,275 children were enrolled. Of these, 64 cases had mixed rotavirus-bacterial infections and were not included in the analysis.
§ P value from Pearson’s chi-square test of independence, or for continuous data, analysis of variance was used. When the chi-square test was statistically significant, then a series of chi-square tests or t tests were calculated to determine which enteropathogens differed by that variable. Results of these tests are reported in the text.
n (%)
** Mean number of stools in 24 hours before clinical evaluation.
Note: Columns may not total to n because of missing data, and percent may not total 100 because of rounding errors.
Diarrhea type
    Acute watery21 (81)¶185 (93)13 (72)203 (99)688 (91)1,110 (93)0.001
    Dysentery2 (8)5 (3)1 (6)1 (0)18 (2)27 (2)
    Persistent3 (11)8 (4)4 (22)0 (0)47 (6)62 (5)
Pattern
    Mean number of stools**669871,202 (7)< 0.001
    Mean days to evaluation544341,208 (4)0.02
History of fever
    Present24 (92)165 (83)15 (83)161 (79)646 (86)1,011 (84)0.12
    None2 (08)33 (17)3 (17)43 (21)106 (14)187 (16)
History of blood
    Much1 (4)1 (0)2 (11)0 (0)0 (1)14 (1)< 0.0001
    Little2 (8)7 (4)2 (11)0 (0)39 (5)50 (4)
    None23 (88)190 (96)14 (78)202 (100)703 (93)1,132 (95)
History of vomiting
    Yes16 (62)134 (67)13 (68)178 (87)535 (70)876 (72)< 0.0001
    No10 (38)67 (33)6 (32)26 (13)224 (30)333 (28)
History of seizures
    Yes2 (8)3 (1)4 (22)2 (1)25 (3)36 (3)< 0.0001
    No24 (92)198 (99)14 (78)201 (99)733 (97)1,170 (97)
History of mucoid stools
    Yes21 (84)125 (63)10 (56)96 (47)512 (81)764 (64)< 0.0001
    No4 (16)75 (37)8 (44)106 (52)124 (20)434 (36)
Rectal temperature
    ≥ 40.00 (0)3 (2)0 (0)1 (0)13 (2)17 (1)0.70
    ≥ 38.27 (27)33 (16)5 (26)38 (19)126 (17)209 (17)
    < 38.219 (73)*165 (82)14 (74)165 (81)621 (82)984 (81)
Dehydration
    Severe0 (0)2 (1)1 (5)6 (3)12 (2)21 (2)0.0006
    Some4 (15)45 (22)6 (32)80 (39)189 (25)324 (27)
    None22 (85)154 (77)12 (63)118 (58)560 (74)866 (72)
Hospitalized
    Yes5 (19)56 (28)6 (32)91 (45)226 (30)384 (32)0.0004
    No21 (81)145 (72)13 (68)113 (55)535 (70)827 (68)
Figure 1.
Figure 1.

Monthly cases of diarrhea associated with Campylo-bacter, enterotoxigenic E. coli (ETEC), Shigella, rotavirus, and other enteropoathogens among children less than 6 years old brought for treatment to Abu Homos District or Benha Fever Hospital, Arab Republic of Egypt, May 2000 to May 2002.

Citation: The American Journal of Tropical Medicine and Hygiene Am J Trop Med Hyg 74, 1; 10.4269/ajtmh.2006.74.148

*

Address correspondence to Thomas F. Wierzba, Ph.D., M.P.H., 6190 Kathmandu Place, Dulles, VA 20189. E-mail: wierzbat@who.org.np

Authors’ addresses: Thomas F. Wierzba, 6190 Kathmandu Place, Dulles, VA, 20189, Telephone: +977-1-444-4950, Fax: +977-1-553-0150, E-mail: wierzbat@who.org.np. Ibrahim Adib Abdel-Messih, U.S. Naval Medical Research Unit No. 3, PSC 452, Box 5000, FPO AE 09835, Telephone: +20-2-342-1375, Fax: +20-2-342-9625, E-mail: adibi@namru3.med.navy.mil. Remon Abu-Elyazeed, 150 Beach Road #22-00, Gateway west, Singapore 189720, Telephone: 65-232 8338, Fax: 65-6732 8678, E-mail: remon.abu-elyazeed@gsk.com. Shannon D. Putnam, U.S. Naval Medical Research Unit No. 2, FPO AP 96520, Telephone: +62-21-421-4457, Fax: +62-21-424-4507, E-mail: putnam@namru2.org. Karim A. Kamal, U.S. Naval Medical Research Unit No. 3, PSC 452, Box 5000, FPO AE 09835, Telephone: +20-2-342-1375, Fax: +20-2-342-9625, E-mail: kamalk@menanet.net. Patrick Rozmajzl, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD 20910-7500, Telephone: 1-301-319-9667, Fax: 301-319-7460, E-mail: rozmajzlp@nmrc.navy.mil. Salwa F. Ahmed, U.S. Naval Medical Research Unit No. 3, PSC 452, Box 5000, FPO AE 09835, Telephone: +20-2-342-1375, Fax: +20-2-342-9625, E-mail: fouads@namru3.med.navy.mil. Hind I. Shaheen, U.S. Naval Medical Research Unit No. 3, PSC 452, Box 5000, FPO AE 09835, Telephone: +20-2-342-1375, Fax: +20-2-342-9625, E-mail: shaheenh@namru3.med.navy.mil. Abdel Fatah, Benha Fever Hospital, Benha, Qalubya Governorate, Egypt, Telephone: +20-2-421764, Fax: +20-2-421764. Khaled Zabedy, Abu Homos District Hospital, Beheira Governorate, Egypt, Telephone: +20-45-256 0044, Fax: +20-45-256 0130. John Sanders, U.S. Naval Medical Research Unit No. 3, PSC 452, Box 5000, FPO AE 09835, Telephone: +20-2-342-1375, Fax: +20-2-342-9625, E-mail: sandersj@namru3.navy.med.mil. Robert Frenck, U.S. Naval Medical Research Unit No. 3, PSC 452, Box 5000, FPO AE 09835, Telephone: +20-2-342-1375, Fax: +20-2-342-9625, E-mail: rfrenck@uclacvr.labiomed.org.

Acknowledgments: The authors thank Dr. Anne Marie Svennerholm for providing the reagents used in testing for enterotoxigenic E. coli and Ms. Manal Mostafa for assisting with the data management and analysis of the study. This study was approved by institutional review boards at the Naval Medical Research Unit No. 3 in compliance with all Federal regulations governing the protection of human subjects. All subjects or their guardians gave voluntary, informed consent for participation prior to enrollment in this study.

Financial support: Global Emerging Infections System (GEIS), Work Unit No.: 847705.82000.25GB.E0018

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Author Notes

Reprint requests: Thomas F. Wierzba, Ph.D., M.P.H., 6190 Kath-mandu Place, Dulles, VA 20189, Telephone: +977-1-444-4950, Fax: +977-1-553-0150, E-mail: wierzbat@who.org.np.
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