Elsa Chea-Woo

Lactobacillus casei strain GG in the treatment of infants with acute watery diarrhea: A randomized, double-blind, placebo controlled clinical trial (ISRCTN67363048)

BackgroundAdjuvant therapy to ORT with probiotic bacteria for infants with acute watery diarrhea has been under active investigation. Most studies have been done in the developed world showing benefit only for viral mild gastroenteritis. We evaluated the effect of a milk formula containing one billion (109) cfu/ml of Lactobacillus casei strain GG (LGG) upon duration and severity of diarrhea in infants in an environment with more severe acute diarrhea, where etiologic agents other than rotavirus are involved more frequently, and where mixed infections are more prevalent.MethodsMale infants aged 3–36 months brought for treatment of acute watery diarrhea of less than 48 hours were eligible. After rehydration was completed with the WHOs oral rehydration solution, patients were randomly assigned to receive a milk formula either containing LGG or not. Stool volume was periodically measured using a devise suited to collect stools separate from urine. Duration of diarrhea was estimated based on stools physical characteristics.ResultsEighty nine patients received the placebo milk formula and ninety received the LGG containing formula. Both groups were comparable in their baseline characteristics. Total stool output was significantly larger (p = 0.047) in the LGG group (247.8 ml/kg) than in the placebo group (195.0 ml/kg). No significant differences were found in duration of diarrhea (58.5 hours with LGG vs. 50.4 hours with placebo), rate of treatment failure (21.1% with LGG vs. 18.0% with placebo), and proportion of patients with unresolved diarrhea after 120 hours (12.2% with LGG vs. 12.5% with placebo). The rate of stools with reducing substances after 24 hours of treatment increased significantly in both groups (from 41.4% to 72.2% with LGG and from 45.9% to 68.0% with placebo).ConclusionThis study did not show a positive effect of LGG on the clinical course of acute watery diarrhea. Positive beneficial effects of LGG, as had been reported elsewhere, could have been masked in our study by worsening diarrhea due to transient lactose malabsorption. Further studies with low-lactose or non-lactose conveyors of LGG are desirable.

Impact of lactoferrin supplementation on growth and prevalence of Giardia colonization in children.

We conducted a randomized, double-blind, placebo-controlled trial comparing supplementation with bovine lactoferrin versus placebo for the prevention of diarrhea in children. Comparison of overall diarrhea incidence and prevalence rates found no significant difference between the 2 groups. However, there was a lower prevalence of colonization with Giardia species and better growth among children in the lactoferrin group.

Clinical studies of lactoferrin in children

Much has been learned in recent years about the mechanisms by which breastfeeding improves child health and survival. However, there has been little progress in using these insights to improve pediatric care. The aim of this study was to review all clinical studies of lactoferrin (LF) in children in an effort to determine which interventions may improve pediatric care or require further research. We conducted a systematic and critical review of published literature and found 19 clinical studies that have used human or bovine LF for different outcomes: iron metabolisms and anemia (6 studies), fecal flora (5 studies), enteric infections (3 studies), common pediatric illnesses (1 study), immunomodulation (3 studies), and neonatal sepsis (1 study). Although the efficacies have varied in each trial, the main finding of all published studies is the safety of the intervention. Protection against enteric infections and neonatal sepsis are the most likely biologically relevant activities of LF in children. Future studies on neonatal sepsis should answer critically important questions. If the data from these sepsis studies are proven to be correct, it will profoundly affect the treatment of low birth weight neonates and will aid in the reduction of child mortality worldwide.

Randomized double-blind controlled trial of bovine lactoferrin for prevention of diarrhea in children

OBJECTIVE To determine the effect of bovine lactoferrin (bLF) on prevention of diarrhea in children. STUDY DESIGN We conducted a community-based randomized double-blind placebo controlled trial comparing supplementation with bLF vs placebo. Previously weaned children were enrolled at 12-18 months and followed for 6 months with daily home visits for data collection and supplement administration. Anthropometric measures were done monthly. RESULTS Five hundred fifty-five children were randomized: 277 to bLF and 278 to placebo; 65 dropped out; 147 894 doses were administered (92% compliance). Overall there were 91 446 child-days of observation and 1235 diarrhea episodes lasting 6219 days. The main pathogens isolated during diarrheal episodes were norovirus (35.0%), enteropathogenic E coli (11.4%), Campylobacter (10.6%), enteroaggregative E coli (8.4%), enterotoxigenic E coli (6.9%), and Shigella (6.6%). The diarrhea incidence was not different between groups: 5.4 vs 5.2 episodes/child/year for bLF and placebo, respectively (P = .375). However, the diarrhea longitudinal prevalence was lower in the bLF group vs placebo (6.6% vs 7.0%, P = .017), as well as the median duration of episodes (4.8 vs 5.3 days, P = .046), proportion of episodes with moderate or severe dehydration (1.0% vs 2.6%, P = .045), and liquid stools load (95.0 vs 98.6) liquid stools/child/year, P < .001). There were no adverse events related to the intervention. CONCLUSIONS Although there was no decrease in diarrhea incidence, longitudinal prevalence and severity were decreased with LF.

Bicarbonate versus citrate in oral rehydration therapy in infants with watery diarrhea: A controlled clinical trial*

In a double-blind, randomized trial, we compared the efficacy of bicarbonate-containing oral rehydration solution vs citrate-containing solution in the treatment of infantile diarrheal dehydration and acidosis. Ninety-seven infants 3 to 24 months of age were entered in the study; 49 received bicarbonate-containing solution and 48 citrate-containing solution. The two groups were similar in all respects at the beginning of the study. Oral rehydration was successful (i.e., no intravenously administered fluids were required) in 85% of study patients; the success rate was similar in both treatment groups. Serum total CO2 concentration increased in a similar fashion in both groups, reaching near normal values at 48 hours after admission. We conclude that sodium citrate can be substituted for sodium bicarbonate in the formulation of the orally administered rehydration solution recommended by the World Health Organization for treatment of diarrheal dehydration in infants.

Phylogenetic relationships of Shiga toxin-producing Escherichia coli isolated from Peruvian children

The aim of this study was to determine the prevalence, virulence factors (stx, eae, ehxA and astA) and phylogenetic relationships [PFGE and multilocus sequence typing (MLST)] of Shiga toxin-producing Escherichia coli (STEC) strains isolated from four previous cohort studies in 2212 Peruvian children aged <36 months. STEC prevalence was 0.4 % (14/3219) in diarrhoeal and 0.6 % (15/2695) in control samples. None of the infected children developed haemolytic uraemic syndrome (HUS) or other complications of STEC. stx1 was present in 83 % of strains, stx2 in 17 %, eae in 72 %, ehxA in 59 % and astA in 14 %. The most common serotype was O26 : H11 (14 %) and the most common seropathotype was B (45 %). The strains belonged mainly to phylogenetic group B1 (52 %). The distinct combinations of alleles across the seven MLST loci were used to define 13 sequence types among 19 STEC strains. PFGE typing of 20 STEC strains resulted in 19 pulsed-field patterns. Comparison of the patterns revealed 11 clusters (I-XI), each usually including strains belonging to different serotypes; one exception was cluster VI, which gathered exclusively seven strains of seropathotype B, clonal group enterohaemorrhagic E. coli (EHEC) 2 and phylogenetic group B1. In summary, STEC prevalence was low in Peruvian children with diarrhoea in the community setting. The strains were phylogenetically diverse and associated with mild infections. However, additional studies are needed in children with bloody diarrhoea and HUS.

Rotavirus seasonal distribution and prevalence before and after the introduction of rotavirus vaccine in a peri-urban community of Lima, Peru

We evaluated the monthly distribution of rotavirus diarrhea in a cohort of children 12-24 months of age followed as part of a diarrhea clinical trial in a peri-urban community of Lima. We observed a peak of rotavirus diarrhea in the winter months and a decrease in rotavirus prevalence after the introduction of the rotavirus vaccine in Peru.

High Prevalence and Increased Severity of Norovirus Mixed Infections Among Children 12–24 Months of Age Living in the Suburban Areas of Lima, Peru

In an active diarrhea surveillance study of children aged 12-24 months in Lima, Peru, norovirus was the most common pathogen identified. The percentage of mixed (bacterial and noroviral) infections was significantly higher among norovirus-positive samples (53%) than among norovirus-negative samples (12%). The combination of norovirus with the most common bacterial pathogens was associated with increased clinical severity over that of either single-pathogen norovirus or single-pathogen bacterial infections.

Shiga Toxin-Producing Escherichia coli in Peruvian Children with Bloody Diarrhea

Shiga toxin-producing Escherichia coli (STEC) is not routinely sought in clinical laboratories in developing counties. Among 131 bloody diarrhea samples in Peruvian children <5 years of age, STEC was found in 9.2% and was associated with absence of fever, an observation that may increase suspicion of these pathogens. Because of the significant prevalence of STEC locally, proper diagnostics methods should be implemented in the region.

Comparative analysis of antimicrobial resistance in enterotoxigenic Escherichia coli isolates from two paediatric cohort studies in Lima, Peru

BACKGROUND Antibiotic resistance is increasing worldwide, being of special concern in low- and middle-income countries. The aim of this study was to determine the antimicrobial susceptibility and mechanisms of resistance in 205 enterotoxigenic Escherichia coli (ETEC) isolates from two cohort studies in children <24 months in Lima, Peru. METHODS ETEC were identified by an in-house multiplex real-time PCR. Susceptibility to 13 antimicrobial agents was tested by disk diffusion; mechanisms of resistance were evaluated by PCR. RESULTS ETEC isolates were resistant to ampicillin (64%), cotrimoxazole (52%), tetracycline (37%); 39% of the isolates were multidrug-resistant. Heat-stable toxin producing (ETEC-st) (48%) and heat-labile toxin producing ETEC (ETEC-lt) (40%) had higher rates of multidrug resistance than isolates producing both toxins (ETEC-lt-st) (21%), p<0.05. Only 10% of isolates were resistant to nalidixic acid and none to ciprofloxacin or cefotaxime. Ampicillin and sulfamethoxazole resistance were most often associated with blaTEM (69%) and sul2 genes (68%), respectively. Tetracycline resistance was associated with tet(A) (49%) and tet(B) (39%) genes. Azithromycin inhibitory diameters were ≤15 mm in 36% of isolates, with 5% of those presenting the mph(A) gene. CONCLUSIONS ETEC from Peruvian children are often resistant to older, inexpensive antibiotics, while remaining susceptible to ciprofloxacin, cephalosporins and furazolidone. Fluoroquinolones and azithromycin remain the drugs of choice for ETEC infections in Peru. However, further development of resistance should be closely monitored.