The detection of enteropathogens in acute diarrhea in a family cohort population in rural Egypt

In 8 villages of rural northeastern Egypt, a 2-year study of the etiologic agents associated with episodes of diarrhea was carried out. Stool specimens (3,243) from 3,513 episodes of diarrhea were processed for enteropathogens. The most commonly identified agents in the group with diarrhea were Giardia lamblia (44%), heat stable enterotoxin (ST)-producing enterotoxigenic Escherichia coli (ETEC) (15%), heat labile toxin (LT)-producing ETEC (12%), enteropathogenic E. coli (EPEC) (4%), rotavirus (3%), Shigella (2%) and Salmonella (1%). Isolation rates were increased in cases compared to controls for all agents except G. lamblia and EPEC strains. Rotavirus, Salmonella and ST-producing ETEC were more frequently isolated during cooler months and Shigella and LT-ETEC occurred more commonly in warmer months. Campylobacter, EPEC, Giardia and E. histolytica did not show a discernable seasonal pattern. Rotavirus was primarily associated with diarrhea in infants only. Forty-four percent of children experienced at least 1 bout of rotavirus diarrhea by the age of 3 years. Vomiting was reported in 65% of cases of rotavirus infection. Dehydration was reported in greater than 40% of those with rotavirus-, Salmonella-, Campylobacter-, LT-ETEC- and EPEC-associated illness and in those without an identifiable agent. While rotavirus was implicated in 3% of cases overall, when vomiting or vomiting plus dehydration occurred, rotavirus was identified with a rate of 10% and 12%, respectively. Dysentery was common only in Shigella cases, occurring in 24%. A decrease in occurrence of rotavirus, Campylobacter and possibly EPEC illness was seen in the infants less than 6 months of age who were breast-fed when compared to those who were not.     

Case-control study of endemic diarrheal disease in Thai children

In a year-long, case-control study of endemic diarrheal disease among 1230 Thai children less than five years of age, rotavirus was detected in 20%, Campylobacter in 13%, Shigella in 13%, Salmonella in 12%, and enterotoxigenic Escherichia coli (ETEC) in 9%. The differences in detection of enteric pathogens between patients and controls was significant for rotavirus (P less than .001), Shigella (P less than .001), ETEC that produced heat-labile and heat-stable toxins (LT and ST; P = .005), and ST only (P less than .001). C. jejuni was most significantly associated with diarrhea in children less than 12 months [corrected] old (P = .037) and Salmonella in children less than three months of age (P = .003). Enteropathogenic E. coli (EPEC) that adhered in a localized pattern to HeLa cells was isolated from 7% of patients and 3% of controls less than six months of age. Only 50% of these E. coli strains were of EPEC serotypes. Enteroinvasive E. coli was isolated from 7% of patients more than two years of age, and new serotypes were identified.     

Campylobacter reactive arthritis: a systematic review

OBJECTIVE: To review the literature on the epidemiology of Campylobacter-associated reactive arthritis (ReA). METHODS: A Medline (PubMed) search identified studies from 1966 to 2006 that investigated the epidemiology of Campylobacter-associated ReA. Search terms included: "reactive arthritis," "spondyloarthropathy," "Reiter's syndrome," "gastroenteritis," "diarrhea," "epidemiology," "incidence," "prevalence," and "Campylobacter." RESULTS: The literature available to date suggests that the incidence of Campylobacter ReA may occur in 1 to 5% of those infected. The annual incidence of ReA after Campylobacter or Shigella may be 4.3 and 1.3, respectively, per 100,000. The duration of acute ReA varies considerably among reports, and the incidence and impact of chronic ReA from Campylobacter infection is virtually unknown. CONCLUSIONS: Campylobacter-associated ReA incidence and prevalence varies widely among reviews due to case ascertainment differences, exposure differences, lack of diagnostic criteria for ReA, and perhaps genetics and ages of exposed individuals. At the population level it may not be associated with HLA-B27, and inflammatory back involvement is uncommon. Follow-up for long-term sequelae is largely unknown. Five percent of Campylobacter ReA may be chronic or relapsing (with respect to musculoskeletal symptoms).     

Persistent high risk of diarrhea among foreigners in Nepal during the first 2 years of residence.

Although numerous studies have shown that diarrhea is the most common illness occurring during the first few weeks of travel, systematic studies of the incidence of diarrhea during long-term residence in developing countries have not been performed. We conducted a cohort study of the incidence and etiology of diarrhea among 77 expatriate adults who had lived in Nepal for <2 years. Persons were followed prospectively for up to 1 year (mean, 9 months). The incidence of diarrhea during the surveillance period was 3.3 episodes of diarrhea per person per year, or 0.27 episodes per person per month. The annual attack rate of specific pathogens was 42% for enterotoxigenic Escherichia coli, 32% for Cyclospora species, 16% for Giardia lamblia, 16% for Shigella species, 10% for Campylobacter species, > or =10% for rotavirus, and 6% for Entamoeba histolytica. This study suggests that adult persons from developed countries who move to developing countries such as Nepal remain at high risk for diarrhea during their first 2 years of residence.     

Future vaccines against enteric pathogens

A small number of bacterial agents, including enterotoxigenic Escherichia coli (ETEC), enteropathogenic E. coli (EPEC), Shigella and Vibrio cholerae 01 and one virus, rotavirus, combine to cause a major proportion of the diarrheal illness of public health importance worldwide. Salmonella typhi is by far the major cause of enteric fever. Attempts to develop safe, practical, and effective vaccines against these agents are under way. Examples of vaccine candidates include live oral vaccines against S. typhi, V. cholerae, Shigella, and rotavirus, and inactivated, submit vaccines given parentally or orally against S. typhi, V. cholerae or ETEC. Although the oral attenuated S. typhi vaccine is ready for commercial license, it will be several years before the other vaccines are proven to be practically safe and effective in children and adults.     

Enterotoxins and adhesins of enterotoxigenic Escherichia coli: are they risk factors for acute diarrhea in the community?

A cohort of 228 Mexican children less than 5 years old was followed during the enterotoxigenic Escherichia coli(ETEC) season. The incidence of ETEC diarrhea-associated and asymptomatic infections was determined, and E. coli strains isolated from stool samples were tested for heat-labile and heat-stable toxins and for expression of colonization factor antigens (CFA). Of the children, 61% had at least one ETEC infection. Children with ETEC isolated from stools were more likely to have diarrhea than were ETEC-free age-matched control children (odds ratio [OR] = 4.5; 95% confidence interval [CI] = 2.9-7.0). Strains carrying CFA/IV, CFA/I, or CFA/II were found in 23%, 18%, and 5% of ETEC infections, respectively. The risk of having diarrhea associated with a CFA-expressing versus a CFA-negative ETEC strain was the same (age-adjusted OR = 0.8; 95% CI = 0.4-1.6). These data should be considered in the development of a diarrhea vaccine containing only CFAs.     

Sentinel hospital surveillance for rotavirus diarrhea in the People's Republic of China, August 2001-July 2003

China has the second largest birth cohort in the world and the second highest number of deaths due to rotavirus infection. It is also the only country with a licensed rotavirus vaccine. Chinese policy makers now need credible estimates of the burden of rotavirus disease, to decide about vaccine use. From August 2001 through July 2003, prospective hospital-based surveillance for rotavirus diarrhea among children <5 years of age was conducted in 6 sentinel hospitals. Rotavirus isolates were characterized to determine the G and P genotypes circulating during the study. Of 3149 children who were admitted to the hospitals for diarrhea and for whom screening for rotavirus was performed, 1590 (50%) had positive results of an antigen detection assay. Of all episodes of rotavirus diarrhea, 95% occurred during the first 2 years of life. The most common rotavirus strain was P[8]G3 (49% of episodes), and all the common strains were detected, including G9 strains (4% of episodes). Ongoing efforts are under way to more precisely define the burden of rotavirus diarrhea in urban and rural populations, to assess the proportion of episodes that may be due to unusual or emerging strains, and to estimate the economic burden of rotavirus disease.     

Epidemiology, etiology and pathophysiology of traveler's diarrhea

Traveler's diarrhea (TD) is the most frequent health problem in travelers to developing countries. Several personal and environmental risk factors are at the basis of TD acquisition and are discussed in this paper. TD is caused by a wide range of infectious organisms, ETEC and EAEC bacteria strains being the main enteropathogens incriminated in TD. Other causative bacteria are: Shigella spp., Campylobacter spp., Vibrio spp., Aeromonas spp., Salmonella spp., and Plesiomonas spp. Parasite species are also included: Cyclospora cayetanensis, Giardia lamblia, Cryptosporidium, Entamoeba histolytica, as well as viruses: rotavirus, adenovirus, Norwalk virus. Due to the great diversity of pathogens incriminated, several pathophysiological mechanisms have been described and some of them are still poorly understood. The clinical symptoms present are also quite variable, although inflammatory and non-inflammatory diarrhea have been established as a classical and basic classification of diarrhea.     

Bacterial enteric pathogens in children with acute dysentery in Thailand: increasing importance of quinolone-resistant Campylobacter

Current data on pathogen prevalence and drug resistance patterns are important for treatment and vaccine-development strategies. An etiologic study of acute bacterial dysentery was conducted in children up to 12 years of age in 2 major hospitals in and around Bangkok. Stool samples or rectal swabs and clinical data were collected. Standard microbiological methods were used to detect Salmonella, Shigella, Campylobacter, Vibrio, Aeromonas and Plesiomonas. Pathogenic E. coli (ETEC, EIEC, STEC) was identified by digoxigenin-labeled probes. A total of 623 cases were enrolled: median age 11.0 months (range 1 month-12 years). At least one bacterial pathogen was isolated in 55% of cases. Campylobacter was the most common pathogen found (28%), whereas Salmonella, Shigella and ETEC were isolated from 18%, 9% and 6% respectively. EIEC, Vibrio and Plesiomonas were isolated from <1% and no STEC was detected. C. jejuni serotypes 36, 4 and 11 were the most common. The mean age of cases with Campylobacter was significantly lower than with Shigella (17.9 vs 52.8 months, p<0.001). Clinical presentations of Campylobacter and Shigella infections were compared: fever (28% vs 37%), abdominal colic (62% vs 80%, p<0.05), vomiting (38% vs 70%, p<0.001) and bloody stools (52% vs 48%). The Campylobacter isolates (80% C. jejuni, 20% C. coli) were 90% resistant to ciprofloxacin but sensitive to macrolides. All the Shigella isolates (70% S. sonnei) were sensitive to quinolones. Our study illustrates the increasing importance of quinolone-resistant Campylobacter and the decline of Shigella in the etiology of dysentery in Thailand. The clinical presentation of campylobacteriosis is similar to that of shigellosis, except that the patients may be younger and there may be less association with colic and vomiting; having fecal leukocytes will be >10/HPF. The use of macrolide antibiotics rather than quinolones would be reasonable in children <24 months of age; fluoroquinolones will be ineffective in at least half of culture-positive cases.     

Incidence of severe rotavirus diarrhea in New Delhi, India, and G and P types of the infecting rotavirus strains

A total of 62,475 children <5 years old from a defined population of approximately 500,000 children and adults from slums in New Delhi, India, were assessed for 1 year by means of passive surveillance, to identify children who were hospitalized for diarrhea. The incidence of severe rotavirus diarrhea was estimated, and the G and P types of the infecting rotavirus strains were determined and were correlated with the clinical severity of diarrhea. Of 584 children who were hospitalized with diarrhea, 137 (23.5%) had rotavirus detected in stool specimens (incidence of rotavirus diarrhea-associated hospitalizations, 337 hospitalizations/100,000 children <5 years of age). Most cases of diarrhea (98%) occurred during the first 2 years of life, peaking at 9-11 months of age. Rotavirus-associated diarrhea occurred year-round but was predominant in winter. Among the strains that could be G-typed, G1 was the most common serotype, followed by G9 and G2; 10% of cases of diarrhea were due to mixed G-type infections. Common strains identified in the present surveillance study were P[8]G1, P[4]G2, P[8]G9, P[6]G1, P[6]G9, and P[6]G3. Children infected with G1 strains had a greater risk of developing more-severe cases of diarrhea than did children infected with other rotavirus strains (odds ratio, 2.95; 95% confidence interval, 1.3-6.67).     

The seasonal variation in the microbial agents implicated in the etiology of diarrheal diseases among children in Lao People's Democratic Republic

During 1994-1995, the etiological structure of children's diarrhea was monitored in outpatients at Mahosot Hospital, Vientiane, Lao PDR. Of the 191 children studied, 42% had stool specimens positive for enteropathogens; 22% had rotavirus, 21.5% enteropathogenic E. coli, 4.7% Shigella flexneri, 2.9% Campylobacter jejuni, 2.1% Shigella sonnei, and 0.5% each of Giardia intestinalis and Entamoeba histolytica. No Vibrio cholerae and Salmonella spp. was detected in this monitoring. In children under five years, rotaviruses were detected almost all round the year with a maximum prevalence in January in the dry season. Shigella species were highly detected in June to July in the rainy season.     

Incidence, etiology, and impact of diarrhea among long-term travelers (US military and similar populations): a systematic review

To determine regional estimates of pathogen-specific prevalence and incidence, as well as, describe morbidity associated with diarrhea among deployed US military and similar populations, a systematic review was conducted for publications between January 1990 to June 2005. Point estimates and confidence intervals of pathogen prevalence and travelers' diarrhea incidence were combined in a random effects model and assessed for heterogeneity. In total, 262 studies were identified for potential inclusion, of which 52 fulfilled inclusion criteria. Overall, 38% were from the Middle East, 29% from Southeast Asia, 27% from Latin America/Caribbean, and 6% from sub-Saharan Africa. Median duration of travel was 1.5 months (interquartile range, 1-3 months). Enterotoxigenic Escherichia coli (ETEC), Campylobacter, and Shigella were identified as causing 38-45% of diarrhea, with regional and population differences. Incidence based on self-report was higher than studies using passive surveillance or clinic-based methods (29 versus 7 versus 6 episodes per 100 person-months, respectively) without regional differences.     

Rotavirus prevalence in the primary care setting in Nicaragua after universal infant rotavirus immunization

Nicaragua was the first developing nation to implement universal infant rotavirus immunization with the pentavalent rotavirus vaccine (RV5). Initial studies of vaccine effectiveness in Nicaragua and other developing nations have focused on the prevention of hospitalizations and severe rotavirus diarrhea. However, rotavirus diarrhea is more commonly treated in the primary care setting, with only 1-3% of rotavirus cases receiving hospital care. We measured the prevalence of rotavirus infection in primary care clinics in León, Nicaragua, after introduction of the immunization program. In the post-vaccine period, 3.5% (95% confidence interval = 1.9-5.8) of children seeking care for diarrhea tested positive for rotavirus. A high diversity of rotavirus genotypes was encountered among the few positive samples. In conclusion, rotavirus was an uncommon cause of childhood diarrhea in this primary care setting after implementation of a rotavirus immunization program.     

Microbiologic and clinical study of acute diarrhea in children in Aswan, Egypt

Children with diarrhea presenting to a Government Rehydration Center in Aswan, Egypt, were investigated to determine the etiology and clinical presentation of acute childhood diarrhea in southern Egypt. Among 126 outpatients and 25 inpatients with diarrhea (mean age 18 months), enterotoxigenic Escherichia coli (ETEC) (17% of cases), Cryptosporidium (9%), Salmonella spp. (7%), Campylobacter jejuni/coli (7%), and Shigella spp. (5%) were the most common enteropathogens identified during the high incidence season of July. Enteropathogens were isolated as often from inpatients as outpatients, except for Salmonella spp. and Cryptosporidium, which were recovered more often from inpatients. Salmonella-infected children, in particular, were more ill, feverish, and dehydrated on presentation than other children, resulting in more frequent hospitalization. Except for Salmonella-infected children, children with acute diarrhea usually presented without severe dehydration, which may have been due to frequent initiation of oral rehydration therapy (ORT) by mothers trained by local health care providers. A potential environmental source of ETEC was identified in clay water storage containers commonly used in this area.     

Development of pathogenicity-driven definitions of outcomes for a field trial of a killed oral vaccine against enterotoxigenic Escherichia coli in Egypt: application of an evidence-based method

BACKGROUND: To design an efficacy trial of a killed oral vaccine against enterotoxigenic Escherichia coli (ETEC) diarrhea in Egyptian children, we derived for ETEC diarrhea an empirical definition that increased the probability that diarrhea associated with excretion of ETEC was caused by the detected ETEC. METHODS: We conducted a cohort study of 397 Egyptian children <24 months old and monitored them until they were 3 years old. Vaccine-preventable (VP) ETEC was defined as ETEC expressing >/=1 of the toxin- (heat-labile [LT] toxin) and colonization-factor antigens (CFA I, II, and IV) in the vaccine. RESULTS: Although fecal excretion of VP-ETEC was highly associated with diarrhea, excretion of LT-ETEC per se was not related to diarrhea (adjusted odds ratio [OR(A)], 1.16 [95% confidence interval [CI], 0.90-1.49]). The fecal excretion of antigenic types of VP-ETEC other than LT-ETEC (non-LT VP-ETEC) was highly associated with diarrheal symptoms (OR(A), 3.91 [95% CI, 2.78-5.49]; P<.001), and this association was greater for nonbloody than for bloody diarrhea. CONCLUSIONS: Because the vaccine had been anticipated to protect primarily against symptomatic ETEC diarrhea, these results indicate that the primary-outcome definition of ETEC diarrhea for the trial should be restricted to nonbloody diarrheal episodes associated with fecal excretion of non-LT VP-ETEC.     

A comparative study of enterotoxigenic Escherichia coli, Shigella, Aeromonas, and Vibrio as etiologies of diarrhea in northeastern Thailand

The incidence of enterotoxigenic Escherichia coli (ETEC), Shigella, Aeromonas, and Vibrio was determined in patients with diarrhea seen at a hospital in northeastern Thailand, and compared with the incidence of these bacteria in household contacts and their neighbors. ETEC was identified in 17%, Shigella in 9%, Aeromonas in 9%, V. parahaemolyticus in 5%, and non-01 V. cholerae in 2% of 299 patients with diarrhea. These five species of bacteria were isolated more often from patients with diarrhea than persons without diarrhea (P less than 0.001). ETEC was found more often in household contacts (22/141) and neighbors (18/147) of index cases than in persons living in homes not associated with ETEC infections (32/1,318; P less than 0.001). While Shigella was isolated less often in family contacts (3/76) and neighbors (4/93) of patients with shigellosis, this enteric pathogen was also isolated more often from contacts than persons not associated with Shigella infection (13/1,437; P less than 0.001). Both Aeromonas and non-01 V. cholerae can also be enteric pathogens; further efforts should be made to define the enteropathogenicity of these bacteria.     

Protective effect of WC3 vaccine against rotavirus diarrhea in infants during a predominantly serotype 1 rotavirus season

We used a double-blind, placebo-controlled trial to study the efficacy of WC3 rotavirus vaccine administered to 104 infants (ages, three to 12 months) before the rotavirus season. Forty-nine infants received vaccine; 55 received placebo. Rotavirus disease during this season was predominantly caused by a serotype 1 strain. In placebo recipients there were 14 cases of rotavirus diarrhea (attack rate, 25%); 11 were moderate to severe (attack rate, 20%). Vaccinees experienced only three cases of rotavirus disease (attack rate, 6.1%), all mild. When all cases (whether associated with rotavirus or not) of clinically significant diarrhea (CSD) were evaluated, WC3 vaccine provided statistically significant (P less than .01) protection against the total number of episodes of CSD and reduced the number of days of CSD-associated diarrhea, vomiting, fever, or illness. Seventy-one percent of the WC3-vaccinated infants had serum antibody responses to the vaccine. The 14 placebo recipients who experienced natural disease predominantly had antibody responses to serotype 1. Sera taken after the rotavirus season revealed a nearly identical rate (40%) of natural rotavirus infection in the vaccinated and placebo groups.     

Protective immunity after natural rotavirus infection: a community cohort study of newborn children in Guinea-Bissau,west Africa

To study the natural history of rotavirus infection and to determine the protection it confers against reinfection and diarrhea, 200 newborns in Guinea-Bissau were prospectively followed for up to 2 years. Rotavirus was detected in stool specimens collected weekly. By age 2 years, the incidence of primary rotavirus infection was 74%. In the first 3 months of life, 17% of the infections were diarrhea associated, compared with 60% at 9-11 months; after age 18 months, all infections were asymptomatic. A primary infection conferred 52% (95% confidence interval [CI], 16% to 73%) and 70% (95% CI, 29% to 87%) protection against subsequent rotavirus infection and rotavirus diarrhea, respectively. The protection was 66% (95% CI, 24% to 85%) against reinfection within the same epidemic, compared with 34% (95% CI, -29% to 67%) against reinfection in any subsequent epidemic. The high level of protection against symptomatic rotavirus infection provides an important incentive for development of a rotavirus vaccine.     

Diarrhoea in elderly people: aetiology, and clinical characteristics

We examined the characteristics of elderly people attending the Dhaka Hospital of ICDDR,B. The hospital has a diarrhoeal disease surveillance system that enrols a 2% systematic sample of all patients visiting the hospital. We reviewed data of all patients enrolled into the surveillance system (n = 13,782) over the period 1996-2001 to identify patients aged 60 y and above for inclusion into the current study (4% of all surveillance patients; n = 478). V. cholerae O1 was the most common enteric pathogen isolated from faecal culture of the patients (20%), followed by ETEC (13%), Shigella (11%), V. cholerae O139 (10%), Campylobacter jejuni (5%), Salmonella (3%), EPEC (2%), rotavirus (4%), and E. histolytica (2%). The isolation rate of V. cholerae O139 and Shigella was higher among the elderly compared to adults (15-59 y of age, 10% vs 6%, and 11% vs 7% respectively; p < 0.05 for both comparisons). Compared to 15-59-y-olds, a significantly higher proportion of the elderly had visible blood in stools (8% vs 5%), required short-stay ward admission (86% vs 82%) or referral (1% vs < 1%) to a health facility. Early initiation of oral or i.v. rehydration therapy, prompt referral, and immediate clinical diagnosis for assessment of the need for antibiotic therapy might be beneficial for the elderly.     

Symptoms of food-borne diseases and gastroenteritis in Kyushu, Japan

In this study we analyzed the symptoms of gastroenteritis or food-borne disease caused by the 10 most prevalent pathogens: Norovirus, Salmonella, Vibrio parahaemolyticus, Campylobacter jejuni, Clostridium perfringens, Shiga toxin-producing Escherichia coli (STEC), enterotoxigenic E. coli (ETEC), Shigella sonnei/flexneri (Shigella), Staphylococcus aureus, and emetic-type Bacillus cereus. The symptoms diarrhea, vomiting, fever, abdominal pain, and headache, and the incubation period in 646 cases in 10 districts of Kyushu between January 2000 and December 2004 were recorded. The pathogen with the shortest mean incubation period was B. cereus (0.8 h), and was followed by S. aureus (3.3 h), C. perfringens (10.7 h) and V. parahaemolyticus (16.4 h). All the patients infected with B. cereus and S. aureus developed symptoms within 6 hours, and those infected with V. parahaemolyticus and C. perfringens developed symptoms within 24 hours. Bloody diarrhea was associated with STEC and Shigella, but rare with other pathogens. Vomiting was associated with almost all cases of S. aureus and B. cereus infection, and occurred in 71.5% of the Norovirus cases and 56.1% of the V. parahaemolyticus cases. Vomiting was less common in the C. perfringens (22.0%) and the ETEC and STEC (both about 5%). Bloody diarrhea, abdominal pain, and vomiting were statistically significantly more common with STEC 0157 infection than with STEC non-0157 infection. Since the cases analyzed in this study included all degrees of illness, mild to severe, and a wide range of ages, the information obtained will serve as a good reference material for administrative and laboratory work when an outbreak takes place.