Effectiveness of Mix-and-Match Vaccination in Preventing SARS-CoV-2 Omicron Variant Infection in Taiwan: A Test-Negative Control Study.

This study aimed to evaluate the effectiveness (VE) of mix-and-match vaccination against SARS-CoV-2 Omicron variant infection and severe outcomes. An SARS-CoV-2 PCR-confirmed retrospective cohort from Chang Gung Medical System in Taiwan was constructed. Vaccination records were tracked from the National Immunization Information System and categorized by different regimens or unvaccinated status. The main outcomes are VE against PCR-confirmed infection and COVID-19-associated moderate to severe disease. Participants were observed during the Omicron wave from March to August 2022. Of 298,737 PCR testing results available, 162,219 were eligible for analysis. VE against infection was modest, ranging from 38.3% to 49.0%, while mRNA-based vaccine regimens revealed better protection against moderate to severe disease, ranging from 80.8% to 90.3%. Subgroup analysis revealed lower VE among persons with major illness in preventing moderate to severe disease. For young adults, the VE of protein-based vaccine regimens showed a comparable protection with other mixed vaccine regimens. The mix-and-match vaccination strategy provided modest clinical effectiveness in preventing Omicron variant infection. mRNA vaccine-based regimens were superior to other regimens against moderate to severe disease especially in older adults. The mix-and-match vaccination strategy could be an alternative to prevent COVID-19 in unstable vaccine supply regions.

Risk reduction analysis of mix-and-match vaccination strategy in healthcare workers during SARS-CoV-2 Omicron variant predominant period: A multi-center cohort study in Taiwan.

This study investigated the relative effectiveness of a mix-and-match vaccination strategy, primarily comprising ChAdOx1 nCOV-19, mRNA-1273, BNT162b2, and a protein-based vaccine, MVC-COV1901, against COVID-19 in a healthcare worker (HCW) cohort in Taiwan during a period when the Omicron variant was predominant. The analysis included a total of 21,729 HCWs and recorded 3,672 infections with no severe disease nor death. Two main findings were observed from the study. Firstly, for those with ChAdOx1 nCOV-19 as primary series, a booster dose with BNT162b2 was associated with a small decrease in the risk of acquiring infection compared to those with mRNA-1273 as a booster (Adjust hazard ratio [Adj HR] 0.864; 95% confidence interval [CI] 0.761‒0.981, P = .024). Secondly, for HCWs receiving an mRNA-1273 booster, compared to those receiving ChAdOx1 nCOV-19 as the primary series, mixed primary series and homologous mRNA-1273 primary series were associated with a higher (Adj HR 1.144; 95% CI 1.021‒1.282, P = .021) and lower risk (Adj HR 0.735; 95% CI 0.671‒0.805, P < .001) of acquiring infection, respectively. Our study demonstrated that mix-and-match vaccination strategy may be associated with different level of risk reduction in acquiring infection, and sizable, prospective studies are encouraged to further elucidate our observation.

Marine prebiotics mediate decolonization of Pseudomonas aeruginosa from gut by inhibiting secreted virulence factor interactions with mucins and enriching Bacteroides population.

BACKGROUND: Pseudomonas aeruginosa intestinal carriage rates are significantly higher in immunosuppressed individuals and hospitalized patients who therefore have increased risk of infections and antibiotic-associated diarrhea. To combat intestinal dysbiosis and decolonize P. aeruginosa from gastrointestinal tract, we investigated the anti-adherence and gut microbiota modulation properties of marine prebiotic fucoidans. METHODS: Proteomic analysis of culture supernatant was performed by LC-MS/MS. Using lectin-based enzyme-linked immunosorbent assay, hemagglutinin domain interaction and inhibition with biomolecules were studied. We investigated the role of nutritional grade fucoidans in a mouse model and used 16S ribosomal RNA sequencing to examine fecal microbiota composition. RESULTS: Analysis of culture supernatant proteins indicated the secretion of two-partner secretion (TPS) family proteins, including TpsA1/CdiA2 and TpsA2/CdiA1. Lectin like activity at the N-terminal of TpsA due to a conserved hemagglutinin domain (Pfam identifier [ID] PF05860) mediates binding to mucins that carry multiple fucosylated glycans. Fucose-rich sulfated polysaccharides (fucoidans) and sulfated dextrans were found to be potent inhibitors of the recombinant N-terminal hemagglutinin domain of TpsA (TpsA-NT-HAD) binding to mucins. In a mouse model, antibiotic-induced dysbiosis was essential for P. aeruginosa gastrointestinal colonization. After prophylactic oral fucoidans supplementation, a higher proportion (60%) of the mice were decolonized over time and resisted re-colonization, this was associated with remarkable expansion of Bacteroides (post-infection day-3 abundance, 29-50%) and consequential reductions in bloom of Enterobacteriaceae and Enterococcaceae populations. In the non-supplemented group, Parabacteroides mediated recovery from dysbiosis but failed to decolonize P. aeruginosa. CONCLUSIONS: Supplementing diet with marine prebiotic fucoidans can mediate earlier recovery from dysbiosis and decolonization of P. aeruginosa from gut by inhibiting secreted virulence factor (TpsA/CdiA) interaction with mucins and promoting the growth of beneficial Bacteroides population. We suggest the prophylactic use of nutritional grade fucoidans to decolonize P. aeruginosa from gastrointestinal tract of at-risk individuals to prevent infection and transmission of colonizing P. aeruginosa.

Association between histo-blood group antigens and Pseudomonas aeruginosa-associated diarrheal diseases.

BACKGROUND: Pseudomonas aeruginosa is not a common enteric pathogen. The association between human histo-blood group antigens (HBGAs) and P. aeruginosa enteric infection has not yet been studied. METHODS: We collected stool samples from healthy children under 2 years of age for P. aeruginosa gut colonization rate. Saliva samples were collected from patients with P. aeruginosa-associated diarrheal diseases and normal healthy children. Genomic DNA was extracted from saliva samples for ABO blood group typing and FUT2 genotyping. Lewis phenotype was detected using ELISA assay. RESULTS: A total of 85 patients with P. aeruginosa-associated diarrheal diseases and 105 healthy children were enrolled for collecting saliva specimens. The stool colonization rate was 5/101 (5%) in healthy children, 4/58 (6.9%) in infants, and 1/43 (2.3%) in children 1-2 years old, respectively. Blood group A was more frequent in patients with P. aeruginosa-associated diarrheal diseases 24/77 (31.2%) than in healthy children 18/102 (17.6%) (P = 0.035). All patients and healthy children were secretor positive. The distribution of weak-secretor genotype Se385/Se385 was 23/84 (27.4%) in patients with P. aeruginosa-associated diarrheal diseases and 17/104 (16.3%) in healthy children, respectively (P = 0.06). Patients with P. aeruginosa-associated diarrheal diseases had a higher percentage of Lea+b+ phenotype 25/81 (30.9%) than healthy children 17/105 (16.2%) (P = 0.018). There was no association between ABO or secretor or Lewis status with the clinical severity of P. aeruginosa-associated diarrheal diseases. CONCLUSION: Infants had a higher gut P. aeruginosa colonization rate than children. Children with blood group A and Lea+b+ phenotype are prone to P. aeruginosa-associated diarrheal diseases.

Titers and breadth of neutralizing antibodies against SARS-CoV-2 variants after heterologous booster vaccination in health care workers primed with two doses of ChAdOx1 nCov-19: A single-blinded, randomized clinical trial.

OBJECTIVES: We conducted a single-blinded, randomized trial to evaluate the safety, reactogenicity, and immunogenicity of heterologous booster vaccination in health care workers (HCW) who had received two doses of ChAdOx1 nCov-19. METHODS: HCW who had at least 90 days after the second dose were enrolled to receive one of the four vaccines: BNT162b2 (30 µg), half-dose mRNA-1273 (50 µg), mRNA-1273 (100 µg), and MVC-COV1901 (15 µg). The primary outcomes were humoral and cellular immunogenicity and secondary outcomes assessed safety and reactogenicity at 28 days post-booster. RESULTS: MVC-COV1901 Three hundred and forty HCW were enrolled: 83 received BNT162b2 (2 excluded), 85 half-dose mRNA-1273, 85 mRNA-1273, and 85 MVC-COV1901. mRNA vaccines had more reactogenicity than protein vaccine. The fold-rise of anti-spike IgG geometric mean titer was 8.4 (95% CI 6.8-10.4) for MVC-COV1901, 32.2 (27.2-38.1) for BNT162b2, 47.6 (40.8-55.6) for half-dose mRNA-1273 and 63.2 (53.6-74.6) for mRNA-1273. The live virus microneutralization assays (LVMNA) against the wild type, alpha and delta variants were consistent with anti-spike IgG for all booster vaccines. The LVMNA in the four groups against omicron BA.1 variant were 6.4 to 13.5 times lower than those against the wild type. All booster vaccines induced a comparable T cell response. CONCLUSIONS: Third dose booster not only increases neutralizing antibody titer but also enhances antibody breadth against SARS-CoV-2 variants. mRNA vaccines are preferred booster vaccines for those who received primary series of ChAdOx1 nCov-19.

Validation of a point-of-need diagnostic tool for rapid diagnosis of norovirus gastroenteritis.

BACKGROUND: The genogroups GI and GII of norovirus (NoV) ribonucleic acid (RNA) genetic variants are the most prevalent cause of acute gastroenteritis outbreaks, especially in children, worldwide. A fast, accurate and convenient tool for diagnosis of NoV may be preferable to the more complicated performance of real-time reverse transcription-polymerase chain reaction (RT-PCR). METHODS: In this study, we developed and evaluated a tool using insulated isothermal PCR (iiPCR)-mediated POCKIT Central NoV GI and NoV GII assay systems for diagnosis of NoV infection in pediatric patients suspected with gastroenteritis. RESULTS: Performance of POCKIT Central Norovirus GI and GII assays using RT-iiPCR, compared to regular real-time RT-PCR showed the same diagnosis rate to NoV GI (100% of total percent agreement and 1.0 of Cohen's kappa value) and a similar detection rate to norovirus GII (96.3% of total percent agreement and 0.92 of Cohen's kappa value). In exclusivity tests, the POCKIT Central NoV GI and GII assays showed negative results to other viruses, indicating that the assays may be a NoV-specific detection tool. CONCLUSION: POCKIT Central NoV GI and GII Assay systems can provide a simple, rapid, sensitive, and specific point-of-need diagnostic tool for the detection of NoV GI and GII RNAs in clinical specimens from children with acute gastroenteritis.

Nasal Methicillin-Resistant Staphylococcus aureus Carriage Among Foreign Workers Recruited to Taiwan From Southeastern Asian Countries.

BACKGROUND: In 2012, we identified the dissemination of methicillin-resistant Staphylococcus aureus (MRSA) sequence type (ST)45 strain in 14 nursing homes in Taiwan and foreign nurse workers, a significant risk factor for MRSA carriage. We conducted this study to understand MRSA carriage and molecular characteristics among foreign workers recruited from Southeastern Asian countries. METHODS: A cross-sectional study involving a total of 1935 foreign workers-929 (arrival group) and 1006 (staying group)-from Vietnam (n = 843), Indonesia (n = 780), the Philippines (n = 239), and Thailand (n = 70) were conveniently recruited during upon-arrival and regular health examination in a regional hospital. A nasal swab was obtained from each participant for detection of MRSA. RESULTS: Overall, MRSA carriage rate was 2.72%, with 2.26% for arrival group and 3.18% for staying group, and 4.74% for Vietnamese, 1.28% for Indonesians, 1.26% for Filipino, and none for Thai workers. Pulsotype AK/ST45 (57%) and pulsotype AX/ST188 (14%) were the top 2 dominant clones for the arrival group, whereas pulsotype D/ST59 (41%) (an endemic community clone in Taiwan) and pulsotype AK/ST45 (19%) were predominant for the staying group. A significant decrease of pulsotype AK/ST45 from 57% to 19% (P = .007) and increase of pulsotype D/ST59 from 4.8% to 41% (P = .004) were found between the arrival and the staying groups. CONCLUSIONS: Approximately 3% of foreign workers recruited from Southeastern Asian countries to Taiwan were colonized with MRSA, including the ST45 strain. However, the MRSA isolates from workers staying in Taiwan were mostly a locally endemic clone and genetically different from those identified from workers on arrival.

Clonal spread of macrolide-resistant Mycoplasma pneumoniae sequence type-3 and type-17 with recombination on non-P1 adhesin among children in Taiwan.

OBJECTIVES: Mycoplasma pneumoniae is currently the most commonly detected bacterial cause of childhood community-acquired pneumonia in several countries. Of note, clonal expansion of macrolide-resistant ST3 occurred in Japan and South Korea. An alarming surge in macrolide resistance complicates the treatment of pneumonia. We aimed to evaluate the clinical manifestation and clonal relatedness of M. pneumoniae circulating among children in Taiwan. METHODS: We prospectively enrolled 626 children with radiologically confirmed pneumonia between 2017 and 2019. An M. pneumoniae infection was suspected on clinical grounds, and tested by real-time PCR and oropharyngeal swab cultures. We used multilocus sequence typing and whole-genome sequencing to characterize the genetic features of M. pneumoniae. RESULTS: A total of 226 children with M. pneumoniae pneumonia were enrolled. Macrolide resistance was found in 77% (174/226) of patients. Multi-locus sequence typing revealed that ST3 (n = 93) and its single-locus variant ST17 (n = 84) were the predominant clones among macrolide-resistant strains. ST17 presented clinical characteristics comparable to its ancestor ST3. On multivariate analysis, macrolide resistance (OR 3.5; 95% CI 1.4-8.5; p 0.007) was independently associated with fever >72 hours after macrolide treatment. By whole-genome sequencing, prediction analysis of recombination sites revealed one recombination site in ST3 and ST17 compared with M29 (a macrolide-sensitive ST3 strain isolated from China in 2005) containing cytadhesin MgpC-like protein, RepMP4 and RepMP5. ST17 had another recombination site containing an adhesin and RepMP2/3. CONCLUSIONS: In addition to macrolide resistance, ST3 and its ST17 variant might evolve through recombination between repetitive sequences and non-P1 cytadhesins for persistent circulation in Taiwan.

A Genome-Based Model to Predict the Virulence of Pseudomonas aeruginosa Isolates.

Variation in the genome of Pseudomonas aeruginosa, an important pathogen, can have dramatic impacts on the bacterium's ability to cause disease. We therefore asked whether it was possible to predict the virulence of P. aeruginosa isolates based on their genomic content. We applied a machine learning approach to a genetically and phenotypically diverse collection of 115 clinical P. aeruginosa isolates using genomic information and corresponding virulence phenotypes in a mouse model of bacteremia. We defined the accessory genome of these isolates through the presence or absence of accessory genomic elements (AGEs), sequences present in some strains but not others. Machine learning models trained using AGEs were predictive of virulence, with a mean nested cross-validation accuracy of 75% using the random forest algorithm. However, individual AGEs did not have a large influence on the algorithm's performance, suggesting instead that virulence predictions are derived from a diffuse genomic signature. These results were validated with an independent test set of 25 P. aeruginosa isolates whose virulence was predicted with 72% accuracy. Machine learning models trained using core genome single-nucleotide variants and whole-genome k-mers also predicted virulence. Our findings are a proof of concept for the use of bacterial genomes to predict pathogenicity in P. aeruginosa and highlight the potential of this approach for predicting patient outcomes.IMPORTANCEPseudomonas aeruginosa is a clinically important Gram-negative opportunistic pathogen. P. aeruginosa shows a large degree of genomic heterogeneity both through variation in sequences found throughout the species (core genome) and through the presence or absence of sequences in different isolates (accessory genome). P. aeruginosa isolates also differ markedly in their ability to cause disease. In this study, we used machine learning to predict the virulence level of P. aeruginosa isolates in a mouse bacteremia model based on genomic content. We show that both the accessory and core genomes are predictive of virulence. This study provides a machine learning framework to investigate relationships between bacterial genomes and complex phenotypes such as virulence.

Characterization of the role of global regulator FliA in the pathophysiology of Pseudomonas aeruginosa infection.

FliA is known to be a sigma factor that regulates bacterial flagella gene expression. Accumulating evidence suggests that FliA is involved in bacterial behavior other than motility. To elucidate the contribution of FliA to Pseudomonas aeruginosa pathophysiology, we analyzed the biological properties and gene expression profiles of a ΔfliA mutant. Transcriptome analysis results demonstrated that the expression levels of flagella biogenesis genes decreased dramatically in the mutant; consequently, the ΔfliA mutant failed to synthesize flagella and exhibited reduced motility. The ΔfliA mutant displayed stronger hemolytic and caseinolytic activities, as well as pyocyanin production. The expression of type 6 secretion system-II genes and interbacterial competition activity was decreased in the ΔfliA mutant. Direct evidence of fliA participation in virulence was obtained from analysis of hypervirulent strain B136-33. Adhesion to and cytotoxicity toward mammalian cells and penetration through cell layers were noted; furthermore, the colonization ability of the fliA::Tn5 mutant in the intestines of laboratory mice was compromised. Notably, the fliA-overexpressing strain displayed phenotypes similar to that of the fliA-defective strain, indicating that optimal FliA levels are critical to bacterial physiology. Our findings indicate that FliA plays diverse roles in P. aeruginosa, not only in flagella biosynthesis, but also in pathophysiology.

Pseudomonas aeruginosa-associated Diarrheal Diseases in Children.

BACKGROUND: The gastrointestinal tract is not the common infection site of Pseudomonas aeruginosa. The role of P. aeruginosa as a causative agent for diarrhea in children without preexisting disease is controversial. METHODS: From 2003 to 2012, we reviewed the records of 259 diarrheal patients less than 5 years of age whose stool culture grew P. aeruginosa. Virulence phenotypes of bacterial isolates were determined in vitro, including cytotoxicity, penetration and adherence to epithelial cells. RESULTS: The presence of P. aeruginosa in children with diarrhea less than 5 years old is 0.91%. P. aeruginosa-associated diarrheal diseases were classified into 4 groups: Shanghai fever (enteric infection and sepsis) (5%), P. aeruginosa enterocolitis (15%), P. aeruginosa-related diarrhea (19%) and antibiotic-associated diarrhea (43%). The remaining patients had coinfection with other pathogens (18%). Shanghai fever was the most severe enteric disease with invasive infection and complications. The clinical features of P. aeruginosa enterocolitis were prolonged fever with bloody or mucoid diarrhea mimicking bacterial enterocolitis. The clinical features of P. aeruginosa-related diarrhea and antibiotic-associated diarrhea were similar to viral or toxin-mediated diarrhea. Compared with other P. aeruginosa-associated diarrheal diseases, patients with Shanghai fever were younger, usually infants, and the characteristic laboratory findings included leukopenia, thrombocytopenia, high C-reactive protein, hyponatremia and hyperglycemia. Except for Shanghai fever, antibiotic treatment is not recommended. Isolates from Shanghai fever were more cytotoxic and adherent than isolates from uncomplicated diarrheal patients. CONCLUSIONS: P. aeruginosa could be an enteric pathogen even in healthy children. Young age and highly virulent bacterial strains were risk factors for Shanghai fever.

Shanghai fever: a distinct Pseudomonas aeruginosa enteric disease.

BACKGROUND: Shanghai fever, a community-acquired enteric illness associated with sepsis caused by Pseudomonas aeruginosa, was first described in 1918. The understanding of Shanghai fever is incomplete. OBJECTIVE: To delineate the clinical features and to examine the host and microbial factors associated with Shanghai fever. METHODS: We prospectively enrolled 27 consecutive previously healthy children with community-acquired P aeruginosa enteritis and sepsis between July 2003 and June 2012. An immunological investigation, including measurement of serum immunoglobulin levels and lymphocyte subpopulations, was performed. The clonal relationship of bacterial isolates was determined by multilocus sequence typing (MLST) and the virulence of isolates was measured using cellular and animal models. RESULTS: The median age of the patients was 7 months; 24 (89%) were aged <1 year. The most common clinical manifestations were fever (100%), diarrhoea (96%) and shock (81%). Leucopenia, thrombocytopenia, high C-reactive protein levels, coagulopathy and hypoalbuminaemia were the key laboratory findings. Necrotising enteritis with or without bowel perforation, ecthyma gangrenosum and seizures were main complications. The death rate was 15%. No common primary immune deficiency was identified. MLST genotypes indicated that isolates from Shanghai fever were non-clonal, but they shared similar phenotypes which were invariably cytotoxic, invasive and adhesive in cellular experiments and caused prolonged gut colonisation and more death than respiratory and laboratory control strains in mice. CONCLUSIONS: Shanghai fever is a sporadic community-acquired disease of previously healthy infants that manifests as sepsis associated with P aeruginosa enteric disease. Both host and microbial factors play a role in pathogenesis.

Wide spread of Tn2006 in an AbaR4-type resistance island among carbapenem-resistant Acinetobacter baumannii clinical isolates in Taiwan.

Carbapenem resistance in Acinetobacter baumannii is a global problem. The purpose of this study was to elucidate current resistance mechanisms of imipenem-resistant A. baumannii (IRAB) in Taiwan and their correlation with patient outcomes. Acinetobacter baumannii clinical isolates from two teaching hospitals in Taiwan were collected in 2009 and were examined by Etest for determination of the minimum inhibitory concentrations (MICs) of imipenem, ceftazidime and ceftriaxone. Primers specific for carbapenemase genes and upstream regions were designed for PCR amplification. Bacterial isolates were genotyped by pulsed-field gel electrophoresis (PFGE). Clinical presentations of patients were analysed retrospectively. Upstream insertion sequence ISAba1 was found in 34 isolates that carried bla(OXA-23), including 28 with transposon Tn2006 (ISAba1-bla(OXA-23)-ISAba1) in an AbaR4-type resistance island and 6 with Tn2008 (ISAba1-bla(OXA-23)), as well as in 8 isolates carrying ISAba1-bla(OXA-51-like). All of these isolates expressed full resistance to imipenem (MIC>32 mg/L). Forty-one different PFGE genotypes were found among 62 isolates. Tn2006 was found in 19 genotypes (46.3%), which is more common than ISAba1-bla(OXA-51-like) (12.2%) (P=0.001). Prior use of carbapenems or extended-spectrum cephalosporins for ≥5 days was the only independent risk factor significantly associated with IRAB infection (odds ratio=361.175). Higher mortality was significantly associated with infection caused by IRAB and ISAba1-bla(OXA-23)-carrying strains compared with infection caused by imipenem-susceptible A. baumannii and ISAba1-bla(OXA-51-like)-carrying strains (P=0.009 and 0.027, respectively). Tn2006 is currently the most common imipenem resistance determinant, which showed a higher ability to spread among A. baumannii and was associated with a higher mortality in IRAB-infected patients.

Seroprevalence of human papillomavirus types 16 and 18 in the general population in Taiwan: implication for optimal age of human papillomavirus vaccination.

BACKGROUND: The optimal age for administration of recently approved prophylactic human papillomavirus (HPV) vaccines remains undetermined. OBJECTIVES: The aim of the study was to explore the age-specific seroprevalence of HPV 16 and 18 in the general population to design an HPV vaccination campaign for Taiwan. STUDY DESIGN: HPV seroprevalence was assessed by virus-like particle (VLP)-based ELISA in 1702 plasma samples collected in 1999. RESULTS: The sample population consisted of 1000 (58.8%) females and 702 (41.2%) males; age ranged from 17 days to 86 years. The age-specific distributions reveal a significant rise in HPV 16 seropositivity commencing at 19-25 years of age and peaking at >60 years. The trend of seropositivity increase with age was also highly significant for HPV 18 (P(Trend)<0.0001). Males had lower overall seroprevalence in gender comparison (7.6% versus 3.85% for HPV 16, 3.9% versus 2.71% for HPV 18), were older at seroconversion (19-25 years versus 26-30 years) with a more obvious seropositivity nadir in middle age. CONCLUSION: The age-specific seroprevalence of HPV 16 and 18 increases in young adults after the age of 18 years, with gender distribution varying. We conclude that the optimal age for universal HPV vaccination in Taiwan is 15 years or below.

Kawasaki disease in infants three months of age or younger.

BACKGROUND AND PURPOSE: Kawasaki disease (KD) is rare in infants < or =3 months of age. This study analyzed the features of KD in 25 infants < or =3 months of age treated from February 1994 to December 2004. METHODS: Basic characteristics, clinical, laboratory, echocardiographic, therapeutic, and follow-up data of the infants were obtained from chart records. RESULTS: There were 19 male and 6 female infants in this cohort. The frequency of the 5 principal clinical features was as follows: changes in lips and oral cavity, 84%; bilateral bulbar conjunctival injection without exudates, 80%; polymorphous exanthem, 68%; cervical lymphadenopathy, 28%; and changes in extremities, 24%. Six infants (24%) fulfilled criteria for KD including fever which persists for 5 or more days with at least 4 of the principal clinical criteria, and the remaining infants were classified as having incomplete KD (all of whom showed coronary involvement). Coronary artery dilatation was found in 20 infants (80%). One infant developed a medium-size aneurysm (5.2 mm), while the others had only coronary arterial ectasia or small aneurysms. Coronary artery aneurysms regressed within 1-year follow-up in all but one infant. No fatal or recurrent case was observed during the study period. CONCLUSIONS: Infants < or =3 months of age with KD usually presented with incomplete clinical features. A high proportion of coronary artery involvement was observed in this series. Echocardiography should be considered in very young infants with unexplained prolonged fever who do not present all of the principal clinical features of KD.

Salmonella enterica serotype Choleraesuis infections in pediatric patients.

OBJECTIVE: Among >2500 nontyphoid Salmonella serotypes, Salmonella enterica serotype Choleraesuis shows a high predilection to cause systemic infections in humans. The objective of this study was to delineate the clinical and microbiologic features of pediatric patients with Salmonella Choleraesuis infections. METHODS: Between May 1999 and February 2003, a total of 33 patients who were <18 years of age had culture-confirmed S Choleraesuis infections. Clinical features, laboratory values, treatment, outcome, and antimicrobial susceptibility patterns of the bacterial isolates were analyzed. RESULTS: There were 24 males and 9 females with a mean age of 3 years. Fever (rectal temperature > or =38 degrees C; 94%) was the most common clinical presentation. Sixteen (52%) had fever lasting >5 days before admission. Only 18 (54%) patients had diarrhea. The most common mode of infection is occult bacteremia without focal infection. Compared with data obtained from adult patients, the gastrointestinal manifestations appeared more frequently seen in pediatric patients. However, among the 18 who presented with diarrhea, 14 had concomitant bloodstream infection. Only 1 patient, who was a case of acute leukemia, died of S Choleraesuis sepsis. Resistance to ceftriaxone, ciprofloxacin, ampicillin, trimethoprim-sulfamethoxazole, and chloramphenicol was found in 6%, 28%, 88%, 76%, and 83% of the isolates, respectively. CONCLUSION: Children with S Choleraesuis infections usually presented with occult bacteremia with mild gastrointestinal involvement. The mortality of S Choleraesuis infections in previously healthy children is low. Ciprofloxacin resistance among S Choleraesuis isolates from pediatric patients was lower than that of isolates from adult patients. In view of the high rate of multidrug resistance, third-generation cephalosporins seem to be the drug of choice for treatment of invasive S Choleraesuis infections.

Clinical and laboratory manifestations of Kikuchi's disease in children and differences between patients with and without prolonged fever.

BACKGROUND: Kikuchi's disease (KD) is characterized by cervical lymphadenopathy with or without fever. It has been recognized worldwide but seldom reported in pediatric patients. METHODS: From January 1985 through December 2001, 64 patients younger than 18 years of age with pathologic proof of KD were enrolled in this study. The clinical manifestations, laboratory data and outcomes were reviewed. RESULTS: There were 35 male patients and 29 female patients with age ranging from 2 to 18 years and a median age of 16. All patients had cervical lymphadenopathy except 1 who had generalized lymphadenopathy. Lymph nodes of 32 patients (50%) were painful or tender or both. Lymphadenopathy was unilateral in 52 patients (82.5%). Lymphadenopathy associated with fever was observed in 21 patients (32.8%). Other signs such as skin rash, hepatomegaly or body weight loss were less common. Twenty-six patients (40.6%) had leukopenia and 2 patients had leukocytosis. Nearly one-fourth of the patients had mild liver dysfunction. Virologic or immunologic studies were normal in most patients. Patients with prolonged fever were more likely to have leukopenia (P < 0.05). All patients recovered, but 1 developed systemic lupus erythematosus 5 years later, and the other had vasculitis syndrome 2 years later. CONCLUSIONS: The clinical presentation of KD in pediatric patients is similar to that of adults. KD is a benign, self-limiting disease; prolonged fever occurred only in 32.8% of pediatric patients in our cohort. Leukopenia was the only feature significantly associated with prolonged fever.