Yao Jong Yang

Clinical Spectrum of Enterovirus 71 Infection in Children in Southern Taiwan, with an Emphasis on Neurological Complications

An outbreak of enterovirus 71 (EV71) infection occurred in Taiwan in 1998. The clinical spectrums and laboratory findings for 97 patients with virus culture-proven EV71 infections were analyzed. Eighty-seven percent of the patients were younger than age 5 years. Hand-foot-and-mouth syndrome occurred in 79% of the children and central nervous system (CNS) involvement in 35%, including nine fatal cases. The predominant neurological presentations were myoclonus (68%), vomiting (53%), and ataxia (35%). Brain stem encephalitis was the cardinal feature of EV71 CNS involvement during this outbreak. Magnetic resonance imaging and pathological findings illustrated that the midbrain, pons, and medulla were the target areas. EV71 brain stem encephalitis can present either with cerebellar signs and an initially mild, reversible course or with overwhelming neurogenic shock and neurogenic pulmonary edema (NPE) resulting in a fatal outcome. Brain stem encephalitis that progressed abruptly to neurogenic shock and NPE was indicative of poor prognosis in this epidemic. Early aggressive treatment and close monitoring of the neurological signs are mandatory to improve the chance of survival.

Universal screening for biliary atresia using an infant stool color card in Taiwan

Biliary atresia is the most common cause of death from liver disease in children. Although the Kasai operation before 60 days of age can significantly improve prognosis, delay in referral and surgery remains a formidable problem worldwide because of difficulties in differentiating it from benign prolonged neonatal jaundice. We established a universal screening system using an infant stool color card to promote the early diagnosis and treatment of biliary atresia. After a pilot regional study in 2002–2003, a national stool color screening system was established by integrating the infant stool color card into the child health booklet given to every neonate in Taiwan since 2004. Within 24 hours of the discovery of an abnormal stool color, this event is reported to the registry center. The annual incidence of biliary atresia per 10,000 live births in 2004 and 2005 was 1.85 (40/216,419) and 1.70 (35/205,854), respectively. The sensitivity of detecting biliary atresia using stool cards before 60 days of age was 72.5% in 2004, which improved to 97.1% in 2005. The national rate of the Kasai operation before 60 days of age increased from 60% in 2004 to 74.3% in 2005. The jaundice‐free rate (<2 mg/dL) at 3 months after the Kasai operation among infants with biliary atresia in 2004–2005 was 59.5% (44 of 74), significantly higher than the historical data of 37.0% in 1976–2000 before the stool card screening program (P = 0.002). Conclusion: Universal screening using the stool color cards can enhance earlier referral, which may ultimately lead to timely performance of the Kasai operation and better postoperative outcome in infants with biliary atresia. (HEPATOLOGY 2008.)

Screening for Biliary Atresia by Infant Stool Color Card in Taiwan

OBJECTIVE. We aimed to detect biliary atresia (BA) in early infancy to prevent additional liver damage because of the delay of referral and surgical treatment and to investigate the incidence rate of BA in Taiwan. METHODS. A pilot study to screen the stool color in infants for the early diagnosis of BA was undertaken from March 2002 to December 2003. We had designed an “infant stool color card” with 7 numbers of different color pictures and attached it to the child health booklet. Parents were then asked to observe their infants stool color by using this card. The medical staff would check the number that the parents chose according to their infants stool color at 1 month of age during the health checkup and then send the card back to the stool color card registry center. RESULTS. The average return rate was ∼65.2% (78184 infants). A total of 29 infants were diagnosed as having BA, and 26 were screened out by stool color card before 60 days of age. The sensitivity, specificity, and positive predictive value were 89.7%, 99.9%, and 28.6%, respectively. Seventeen (58.6%) infants with BA received a Kasai operation within 60-day age period. The estimated incidence of BA in screened newborns was 3.7 of 10000. CONCLUSIONS. The stool color card was a simple, efficient, and applicable mass screening method for early diagnosis and management of BA. The program can also help in estimating the incidence and creating a registry of these patients.

Effects of the infant stool color card screening program on 5-year outcome of biliary atresia in Taiwan.

In Taiwan, a screening system using an infant stool color card to promote the early diagnosis of biliary atresia (BA) was established in 2002. This study aimed to investigate the 5‐year outcome of BA before and after using the screening program. BA patients were divided into three cohorts according to their birth dates. The patients in cohort A (n = 89) were born before the stool card screening program (1990‐2000); those in cohort B (n = 28) were screened by the stool card regional screening program (2002‐2003); and those in cohort C (n = 74) were screened by the stool card universal screening program (2004‐2005). The relative odds ratios were computed using logistic regression to compare the different factors affecting survival time. The rate of age at Kasai operation <60 days was 49.4% and 65.7% in cohorts A and B+C, respectively (P = 0.02). The jaundice‐free (total serum bilirubin <2.0 mg/dL) rate 3 months after surgery was 34.8% and 60.8% in cohorts A and B+C, respectively (P < 0.001). The 3‐year jaundice‐free survival rate with native liver was 31.5% in cohort A and 56.9% in cohort B+C (P < 0.001), whereas the 3‐year overall survival rates were 64.0% and 89.2%, respectively (P < 0.001). The 5‐year jaundice‐free survival rate with native liver was 27.3% in cohort A and 64.3% in cohort B (P < 0.001), and the 5‐year overall survival rates were 55.7% and 89.3%, respectively (P < 0.001). Conclusion: The stool color card screening program for BA allows for earlier Kasai operation, which increases the jaundice‐free rate at 3 months postsurgery. With higher surgical success rates, the 3‐ and 5‐year outcome of BA patients in Taiwan improves remarkably. (HEPATOLOGY 2011.)

Resistance to metronidazole, clarithromycin and levofloxacin of Helicobacter pylori before and after clarithromycin‐based therapy in Taiwan

Background and Aim:  Clarithromycin‐based triple therapy has been commonly applied as the first‐line therapy for Helicobacter pylori eradication. Levofloxacin could serve as an alternative in either first‐line or second‐line regimens. This study surveyed the prevalence of levofloxacin resistance of H. pylori isolates in naive patients and in patients with a failed clarithromycin‐based triple therapy.

Lactobacillus acidophilus ameliorates H. pylori-induced gastric inflammation by inactivating the Smad7 and NFκB pathways.

BackgroundH. pylori infection may trigger Smad7 and NFκB expression in the stomach, whereas probiotics promote gastrointestinal health and improve intestinal inflammation caused by pathogens. This study examines if probiotics can improve H. pylori-induced gastric inflammation by inactivating the Smad7 and NFκB pathways.ResultsChallenge with H. pylori increased IL-8 and TNF-α expressions but not TGF-β1 in MKN45 cells. The RNA levels of Smad7 in AGS cells increased after H. pylori infection in a dose-dependent manner. A higher dose (MOI 100) of L. acidophilus pre-treatment attenuated the H. pylori-induced IL-8 expressions, but not TGF-β1. Such anti-inflammatory effect was mediated via increased cytoplasmic IκBα and depletion of nuclear NFκB. L. acidophilus also inhibited H. pylori-induced Smad7 transcription by inactivating the Jak1 and Stat1 pathways, which might activate the TGF-β1/Smad pathway. L. acidophilus pre-treatment ameliorated IFN-γ-induced Smad7 translation level and subsequently reduced nuclear NF-κB production, as detected by western blotting.ConclusionsH. pylori infection induces Smad7, NFκB, IL-8, and TNF-α production in vitro. Higher doses of L. acidophilus pre-treatment reduce H. pylori-induced inflammation through the inactivation of the Smad7 and NFκB pathways.

Children of Helicobacter pylori-infected dyspeptic mothers are predisposed to H. pylori acquisition with subsequent iron deficiency and growth retardation

Background.  We tested whether Helicobacter pylori‐infected dyspeptic mothers had a higher rate of H. pylori infection in their children, and whether such H. pylori‐infected children were predisposed to iron deficiency or growth retardation.

Probiotics-Containing Yogurts Suppress Helicobacter pylori Load and Modify Immune Response and Intestinal Microbiota in the Helicobacter pylori-Infected Children

Background:  The benefits of probiotics to the pediatric Helicobacter pylori infection remain uncertain. We tested whether the H. pylori‐infected children have an altered gut microflora, and whether probiotics‐containing yogurt can restore such change and improve their H. pylori‐related immune cascades.

Role of hepatitis B immunoglobulin in infants born to hepatitis B e antigen-negative carrier mothers in Taiwan.

Background. The efficacy of hepatitis B immunoglobulin (HBIG) in infants of hepatitis B e antigen (HBeAg)-negative hepatitis B surface antigen (HBsAg) carrier mothers in Taiwan is not clear. Objective. To describe the responses of infants born to HBeAg-negative carrier mothers receiving HBIG combined with hepatitis B vaccine. Methods. Term babies born to HBeAg-negative carrier mothers were assigned based on chart number to 1 of the 2 treatment groups. Group A infants (n = 94) received 0.5 ml (145 IU) of HBIG within 24 h of birth and 3 subsequent doses of recombinant hepatitis B virus (HBV) vaccine at 3 to 5 days, 1 month and 6 months of age. Group B infants (n = 122) received 3 doses of vaccines only. Infants (n = 19) born to HBeAg-positive carrier mothers were treated like those in Group A and are referred to as Group C. Sera obtained from infants at 2 and 7 months of age were tested for hepatitis B virus (HBV) markers. Results. There were 2 (1%; one in Group A and one in Group B) subclinical breakthrough hepatitis B infections among studied infants. One (5%) child of Group C had asymptomatic HBV infection at the age of 7 months and became a chronic carrier. The rate of protective anti-hepatitis B surface antibody (anti-HBs) titers achieved (>10 mIU/ml) by 2 months of age was significantly higher in Group A than that in Group B (98% vs. 57%, P < 0.001). However, it was not different by 7 months of age. Infants (Group A) immunized with HBIG and vaccine had a significantly higher geometric mean titer (GMT, milli-International Units/ml) of anti-HBs than those (Group B) with vaccines only at 2 months of age (P < 0.001). Conversely at 7 months of age, the GMT of anti-HBs was significantly higher in infants who received vaccine only (P = 0.001). Conclusions. A protective level of antibodies was achieved earlier in those infants receiving both passive and active immunizations. However, infants receiving active immunizations alone achieved a higher GMT at 7 months of age. There was no clear benefit of passive-active vs. active immunization alone for chronic HBV infection in infants of HBsAg-positive, HBeAg-negative mothers.

Prevalence and rapid identification of clarithromycin-resistant Helicobacter pylori isolates in children.

BACKGROUND Little is known about the prevalence of antibiotic-resistant Helicobacter pylori infection in children. Culture and antimicrobial susceptibility testing are generally time-consuming and not a routine in many hospitals. OBJECTIVE To investigate the prevalence of clarithromycin-resistant H. pylori strains in children, to identify those isolates via rapid methodology and to examine the severity of gastritis caused by the antibiotic-resistant H. pylori isolates. METHODS Enrolled were 245 children investigated for H. pylori infection by endoscopic examination. The gastric antral specimens were subjected to DNA extraction and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) with primers specific to the H. pylori 23S rRNA gene. Conventional bacterial cultures were performed simultaneously as the diagnostic standard. Minimal inhibitory concentrations of clarithromycin and metronidazole were determined by E test. This was used as a standard to determine the sensitivity and specificity of the above PCR-RFLP assay. The specimens were processed for histologic examination and evaluated by the updated Sydney system. RESULTS H. pylori was isolated in 67 of the 245 children; 12 (18%) of them were clarithromycin-resistant and 6 (9%) were metronidazole-resistant. No difference in histologic examinations was noted between the antibiotic-resistant and -susceptible strains. We performed PCR-RFLP with all 12 clarithromycin-resistant isolates: 10 had a 23S ribosomal RNA A2144G point mutation; 1 had a mixture of an A2143G point mutant and susceptible strains; and 1 had neither of the 2 mutations. CONCLUSIONS The prevalence of clarithromycin-resistant H. pylori isolates in Taiwanese children is 18%. PCR-RFLP had a high sensitivity (92%) and specificity (100%) for the clarithromycin resistance gene mutation determination. The dominant mutation is A2144G. PCR-RFLP provides a rapid and accurate approach to detect clarithromycin-resistant strains within 24 h.