Time Series Analysis of the Microbiota of Children Suffering From Acute Infectious Diarrhea and Their Recovery After Treatment.

Gut microbiota is closely related to acute infectious diarrhea, one of the leading causes of mortality and morbidity in children worldwide. Understanding the dynamics of the recovery from this disease is of clinical interest. This work aims to correlate the dynamics of gut microbiota with the evolution of children who were suffering from acute infectious diarrhea caused by a rotavirus, and their recovery after the administration of a probiotic, Saccharomyces boulardii CNCM I-745. The experiment involved 10 children with acute infectious diarrhea caused by a rotavirus, and six healthy children, all aged between 3 and 4 years. The children who suffered the rotavirus infection received S. boulardii CNCM I-745 twice daily for the first 5 days of the experiment. Fecal samples were collected from each participant at 0, 3, 5, 10, and 30 days after probiotic administration. Microbial composition was characterized by 16S rRNA gene sequencing. Alpha and beta diversity were calculated, along with dynamical analysis based on Taylor's law to assess the temporal stability of the microbiota. All children infected with the rotavirus stopped having diarrhea at day 3 after the intervention. We observed low alpha diversities in the first 5 days (p-value < 0.05, Wilcoxon test), larger at 10 and 30 days after probiotic treatment. Canonical correspondence analysis (CCA) showed differences in the gut microbiota of healthy children and of those who suffered from acute diarrhea in the first days (p-value < 0.05, ADONIS test), but not in the last days of the experiment. Temporal variability was larger in children infected with the rotavirus than in healthy ones. In particular, Gammaproteobacteria class was found to be abundant in children with acute diarrhea. We identified the microbiota transition from a diseased state to a healthy one with time, whose characterization may lead to relevant clinical data. This work highlights the importance of using time series for the study of dysbiosis related to diarrhea.

Lactobacillus reuteri DSM 17938 shortens acute infectious diarrhea in a pediatric outpatient setting / O Lactobacillus reuteri DSM 17938 reduz a diarreia infecciosa aguda no cuidado pediátrico ambulatorial

OBJECTIVE: Two randomized controlled clinical trials have shown thatLactobacillus (L) reuteri DSM 17938 reduces the duration of diarrhea in children hospitalized due to acute infectious diarrhea. This was the first trial evaluating the efficacy of L. reuteri DSM 17938 in outpatient children with acute infectious diarrhea.METHODS: This was a multicenter, randomized, single-blinded, case control clinical trial in children with acute watery diarrhea. A total of 64 children who presented at outpatient clinics were enrolled. The probiotic group received 1 × 108 CFU L. reuteri DSM 17938 for five days in addition to oral rehydration solution (ORS) and the second group was treated with ORS only. The primary endpoint was the duration of diarrhea (in hours). The secondary endpoint was the number of children with diarrhea at each day of the five days of intervention. Adverse events were also recorded.RESULTS: The mean duration of diarrhea was significantly reduced in the L. reuteri group compared to the control group (approximately 15 h, 60.4 ± 24.5 h [95% CI: 51.0-69.7 h] vs. 74.3 ± 15.3 h [95% CI: 68.7-79.9 h], p < 0.05). The percentage of children with diarrhea was lower in the L. reuteri group (13/29; 44.8%) after 48 h than the control group (27/31; 87%; RR: 0.51; 95% CI: 0.34-0.79,p < 0.01). From the 72nd hour of intervention onwards, there was no difference between the two groups in the percentage of children with diarrhea. No adverse effects related to L. reuteri were noted.CONCLUSION:L. reuteri DSM 17938 is effective, safe, and well-tolerated in outpatient children with acute infectious diarrhea.

OBJETIVO: Dois ensaios clínicos randomizados controlados demonstraram que oLactobacillus (L) reuteri DSM 17938 reduz a duração de diarreia em crianças hospitalizadas devido a diarreia infecciosa aguda. Este é o primeiro ensaio que avalia a eficácia do L. reuteri DSM 17938 em crianças com diarreia infecciosa aguda no ambulatório.MÉTODOS: Ensaio clínico multicêntrico, randomizado, único cego, com grupos paralelos e controlado em crianças com diarreia aguda. Foram inscritas 64 crianças internadas na clínica ambulatorial. O grupo probiótico recebeu 1 × 108 CFU L. reuteri DSM 17938 por cinco dias, além de uma solução de reidratação oral (SRO), e o segundo grupo foi tratado apenas com SRO. O desfecho principal foi a duração da diarreia (em horas). O desfecho secundário foi o número de crianças com diarreia em cada um dos cinco dias da intervenção. Os eventos adversos também foram registrados.RESULTADOS: A duração média da diarreia foi significativamente reduzida no grupoL. reuteri em comparação com o grupo de controle (aproximadamente 15 horas; 60,4 ± 24,5 horas [51,0-69,7 horas, IC de 95%] em comparação com 74,3 ± 15,3 horas [68,7-79,9 horas, IC de 95%], p < 0,05). O percentual de crianças com diarreia foi menor no grupo L. reuteri (13/29; 44,8%) após 48 horas do que no grupo de controle (27/31; 87%) (RR: 0,51; 0,34-0,79; IC de 95%, < 0,01). A partir da 72a hora de intervenção, não havia diferença entre os dois grupos no percentual de crianças com diarreia. Nenhum efeito adverso com relação ao L. reuteri foi observado.CONCLUSÃO: O L. reuteri DSM 17938 é eficaz, seguro e bem tolerado por crianças com diarreia infecciosa aguda no ambulatório.

Children with breakthrough varicella infection requiring hospitalization in Turkey (VARICOMP Study 2008-2013).

INTRODUCTION: Varicella in previously immunized individuals, known as "breakthrough varicella". While the majority of breakthrough cases are mild, some may be severe, requiring hospitalization in previously healthy children or children with an underlying condition. METHODS: This report, as a part of the prospective national pediatric varicella hospitalizations study (including 29 centers, represent 50% of pediatric population) in Turkey, is aimed to evaluate breakthrough varicella infection requiring hospitalization before the routine use of single-dose live varicella vaccine in national program from 2008 to 2013 (<10% of the pediatric age group received a single-dose vaccine). RESULTS: In the time period, 1939 children were hospitalized due to varicella infection in Turkey; 36 children (20 boys, 16 girls, mean age 68.0+37.6 months, all received single dose live varicella vaccine) with breakthrough varicella infection. Breakthrough varicella infection might be severe in previously healthy children (61.1%) and children with immune-compromising conditions (38.9%). The time elapsed between vaccination and hospitalization was approximately 5 years, and neurological complications, mainly encephalitis and meningitis, were the most common reason for hospitalization in previously healthy children. CONCLUSION: Pediatric breakthrough varicella requiring hospitalization have been seen in Turkey, is mainly observed in previously healthy children at 5 years after a single-dose varicella vaccine. The varicella vaccine has been implemented as part of the National Immunization Program in Turkey in 2013 (a single dose at age 12 months). Further surveillance in the same settings could evaluate the effectiveness of national immunization with single-dose varicella vaccine at 12 months of age and potential need for second dose of vaccine.

Lactobacillus reuteri DSM 17938 shortens acute infectious diarrhea in a pediatric outpatient setting.

OBJECTIVE: Two randomized controlled clinical trials have shown that Lactobacillus (L) reuteri DSM 17938 reduces the duration of diarrhea in children hospitalized due to acute infectious diarrhea. This was the first trial evaluating the efficacy of L. reuteri DSM 17938 in outpatient children with acute infectious diarrhea. METHODS: This was a multicenter, randomized, single-blinded, case control clinical trial in children with acute watery diarrhea. A total of 64 children who presented at outpatient clinics were enrolled. The probiotic group received 1×10(8)CFU L. reuteri DSM 17938 for five days in addition to oral rehydration solution (ORS) and the second group was treated with ORS only. The primary endpoint was the duration of diarrhea (in hours). The secondary endpoint was the number of children with diarrhea at each day of the five days of intervention. Adverse events were also recorded. RESULTS: The mean duration of diarrhea was significantly reduced in the L. reuteri group compared to the control group (approximately 15h, 60.4±24.5h [95% CI: 51.0-69.7h] vs. 74.3±15.3h [95% CI: 68.7-79.9h], p<0.05). The percentage of children with diarrhea was lower in the L. reuteri group (13/29; 44.8%) after 48h than the control group (27/31; 87%; RR: 0.51; 95% CI: 0.34-0.79, p<0.01). From the 72nd hour of intervention onwards, there was no difference between the two groups in the percentage of children with diarrhea. No adverse effects related to L. reuteri were noted. CONCLUSION: L. reuteri DSM 17938 is effective, safe, and well-tolerated in outpatient children with acute infectious diarrhea.

Meningitis caused by Neisseria Meningitidis, Hemophilus Influenzae Type B and Streptococcus Pneumoniae during 2005-2012 in Turkey. A multicenter prospective surveillance study.

Successful vaccination policies for protection from bacterial meningitis are dependent on determination of the etiology of bacterial meningitis. Cerebrospinal fluid (CSF) samples were obtained prospectively from children from 1 month to ≤18 years of age hospitalized with suspected meningitis, in order to determine the etiology of meningitis in Turkey. DNA evidence of Neisseria meningitidis (N. meningitidis), Streptococcus pneumoniae (S. pneumoniae), and Hemophilus influenzae type b (Hib) was detected using multiplex polymerase chain reaction (PCR). In total, 1452 CSF samples were evaluated and bacterial etiology was determined in 645 (44.4%) cases between 2005 and 2012; N. meningitidis was detected in 333 (51.6%), S. pneumoniae in 195 (30.2%), and Hib in 117 (18.1%) of the PCR positive samples. Of the 333 N. meningitidis positive samples 127 (38.1%) were identified as serogroup W-135, 87 (26.1%) serogroup B, 28 (8.4%) serogroup A and 3 (0.9%) serogroup Y; 88 (26.4%) were non-groupable. As vaccines against the most frequent bacterial isolates in this study are available and licensed, these results highlight the need for broad based protection against meningococcal disease in Turkey.

The epidemiology and economic impact of varicella-related hospitalizations in Turkey from 2008 to 2010: a nationwide survey during the pre-vaccine era (VARICOMP study).

Varicella can cause complications that are potentially serious and require hospitalization. Our current understanding of the causes and incidence of varicella-related hospitalization in Turkey is limited and sufficiently accurate epidemiological and economical information is lacking. The aim of this study was to estimate the annual incidence of varicella-related hospitalizations, describe the complications, and estimate the annual mortality and cost of varicella in children. VARICOMP is a multi-center study that was performed to provide epidemiological and economic data on hospitalization for varicella in children between 0 and 15 years of age from October 2008 to September 2010 in Turkey. According to medical records from 27 health care centers in 14 cities (representing 49.3% of the childhood population in Turkey), 824 children (73% previously healthy) were hospitalized for varicella over the 2-year period. Most cases occurred in the spring and early summer months. Most cases were in children under 5 years of age, and 29.5% were in children under 1 year of age. The estimated incidence of varicella-related hospitalization was 5.29-6.89 per 100,000 in all children between 0-15 years of age in Turkey, 21.7 to 28 per 100,000 children under 1 year of age, 9.8-13.8 per 100,000 children under 5 years of age, 3.96-6.52 per 100,000 children between 5 and 10 years of age and 0.42 to 0.71 per 100,000 children between 10 and 15 years of age. Among the 824 children, 212 (25.7%) were hospitalized because of primary varicella infection. The most common complications in children were secondary bacterial infection (23%), neurological (19.1%), and respiratory (17.5%) complications. Secondary bacterial infections (p < 0.001) and neurological complications (p < 0.001) were significantly more common in previously healthy children, whereas hematological complications (p < 0.001) were more commonly observed in children with underlying conditions. The median length of the hospital stay was 6 days, and it was longer in children with underlying conditions (<0.001). The median cost of hospitalization per patient was $338 and was significantly higher in children with underlying conditions (p < 0.001). The estimated direct annual cost (not including the loss of parental work time and school absence) of varicella-related hospitalization in children under the age of 15 years in Turkey was $856,190 to $1,407,006. According to our estimates, 882 to 1,450 children are hospitalized for varicella each year, reflecting a population-wide occurrence of 466-768 varicella cases per 100,000 children. In conclusion, this study confirms that varicella-related hospitalizations are not uncommon in children, and two thirds of these children are otherwise healthy. The annual cost of hospitalization for varicella reflects only a small part of the overall cost of this disease, as only a very few cases require hospital admission. The incidence of this disease was higher in children <1 year of age, and there are no prevention strategies for these children other than population-wide vaccination. Universal vaccination is therefore the only realistic option for the prevention of severe complications and deaths. The surveillance of varicella-associated complications is essential for monitoring of the impact of varicella immunization.

Hematuria with mumps infection.

Two cases with macroscopic hematuria as complication of acute mumps infection is reported. The patients have neither been vaccinated against mumps nor had mumps infection earlier. Macroscopic hematuria resolved spontaneously and renal functions did not deteriorate in both the patients. Although mumps has a benign course, mild and rarely severe renal involvement may occur. Therefore, renal functions in patients with hematuria and mumps should be followed closely.