Prothrombin Time Prolongation was the Most Important Indicator of Severe Bleeding in Children with Severe Dengue Viral Infection.

To determine the indicators of severe bleeding in children with severe dengue viral infection (DVI), the medical records of patients aged <15 years admitted to Songklanagarind Hospital in southern Thailand during 1989-2011 were reviewed. Severe-bleeding DVI was defined as needing blood products transfusion owing to DVI-caused bleeding. Of the 238 children with severe DVI according to the World Health Organization 2009 criteria, 44 (18.5%) had severe bleeding, of whom 28 (63.6%) died. The international normalized ratio (INR) had high correlations with both transaminase enzymes (Spearman correlation, rs = 0.67-0.69, p <0.01). Multivariate analysis found that patients who had dengue haemorrhagic fever (DHF) grade IV, platelets <20 000/mm3 and INR ≥ 1.5 had increased risk of severe bleeding with odds ratios (95% confidence intervals) of 3.4 (1.4, 8.6), 2.6 (1.1, 6.2) and 10.6 (4.0, 28.4), respectively. Blood products should be at hand in severe DHF children with high risk of severe bleeding.

Post-licensure, phase IV, safety study of a live attenuated Japanese encephalitis recombinant vaccine in children in Thailand.

BACKGROUND: Japanese encephalitis is a mosquito-borne viral disease endemic in most countries in Asia. A recombinant live, attenuated Japanese encephalitis virus vaccine, JE-CV, is licensed in 14 countries, including Thailand, for the prevention of Japanese encephalitis in adults and children. METHODS: This was a prospective, phase IV, open-label, multicentre, safety study of JE-CV conducted from November 2013 to April 2015, to evaluate rare serious adverse events (AEs). JE-CV was administered to 10,000 healthy children aged 9months to <5years in Thailand as a primary (Group 1) or booster (Group 2) vaccination. Serious AEs (SAEs), including AEs of special interest, up to 60days after administration were evaluated. Immediate Grade 3 systemic AEs up to 30min after JE-CV administration were also described. RESULTS: The median age of participants was 1.1years in Group 1 and 3.8years in Group 2. SAEs were reported in 204 (3.0%) participants in Group 1 and 59 (1.9%) participants in Group 2. Among a total of 294 SAEs in 263 participants, only three events occurring in two participants were considered related to vaccination. All three cases were moderate urticaria, none of which met the definition of AEs of special interest for hypersensitivity. AEs of special interest were reported in 28 (0.4%) participants in Group 1 and 4 (0.1%) participants in Group 2; none were considered related to vaccination. Febrile convulsion was the most frequently reported AE of special interest: 25 (0.4%) participants in Group 1; and 2 (<0.1%) in Group 2. There were no cases of Japanese encephalitis reported. No Grade 3 immediate systemic AEs were reported after any JE-CV vaccination. CONCLUSIONS: Our study did not identify any new safety concerns with JE-CV and confirms its good safety profile. This study was registered on www.clinicaltrials.gov (NCT01981967; Universal Trial Number: U1111-1127-7052).

Outcome of Severe Dengue Viral Infection-caused Acute Liver Failure in Thai Children.

To determine clinical course and outcomes of liver functions in children with dengue viral infection-caused acute liver failure (ALF), the records of patients aged <15 years attending our institution during 1989-2011 were reviewed. Of the 41 ALF patients, 2, 6 and 33 patients had dengue hemorrhagic fever grade II, III and IV, respectively. Multiorgan failure including respiratory failure, massive bleeding and acute kidney injury occurred in 80.0%, 96.0% and 84.0% of the ALF cases, respectively, with an overall fatality rate of 68.3%. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were highest on the day that the patient developed ALF. Lactate dehydrogenase levels had positive correlations with AST (r = 0.95) and ALT (r = 0.87) (all p < 0.01). The median (interquartile range) days before the AST and ALT levels returned to lower than 200 U/L after the ALF were 10.5 (8.8, 12.8) and 10.5 (7.8, 14.0) days, respectively.

Acute respiratory failure and active bleeding are the important fatality predictive factors for severe dengue viral infection.

OBJECTIVE: To determine the outcome of severe dengue viral infection (DVI) and the main dengue fatality risk factors. STUDY DESIGN: The medical records of patients aged <15 years admitted to Songklanagarind Hospital in southern Thailand during 1989-2011 were reviewed. Patients who had dengue hemorrhagic fever (DHF) grades III-IV, organ failure (cardiovascular, respiratory, liver, renal or hematologic), impaired consciousness, or aspartate aminotransferase more than 1,000 units/L, were classified as having severe DVI. To determine the fatality risk factors of severe DVI, the classification trees were constructed based on manual recursive partitioning. RESULTS: Of the 238 children with severe DVI, 30 (12.6%) died. Compared to the non-fatal DVI cases, the fatal cases had higher rates of DHF grade IV (96.7% vs 24.5%), repeated shock (93.3% vs 27.9%), acute respiratory failure (ARF) (100% vs 6.7%), acute liver failure (ALF) (96.6% vs 6.3%), acute kidney injury (AKI) (79.3% vs 4.5%), and active bleeding requiring blood transfusion (93.3% vs 5.4%), all p<0.01. The combined risk factors of ARF and active bleeding considered together predicted fatal outcome with sensitivity, specificity, and negative and positive predictive values of 0.93 (0.78-0.99), 0.97 (0.93-0.99), 0.99 (0.97-1.00), and 0.82 (0.65-0.93), respectively. The likelihood ratios for a fatal outcome in the patients who had and did not have this risk combination were 32.4 (14.6-71.7) and 0.07 (0.02-0.26), respectively. CONCLUSION: Severe DVI patients who have ARF and active bleeding are at a high risk of death, while patients without these things together should survive.

In vitro activity of colistin against multidrug-resistant Pseudomonas aeruginosa isolates from patients in Songklanagarind Hospital, Thailand.

Multidrug-resistant Pseudomonas aeruginosa (MDR-PA) infection creates problems for therapy. Previous studies have found MDR-PA is susceptible to colistin. We studied the in vitro susceptibility of MDR-PA to colistin and determined the minimum inhibitory concentration (MIC). One hundred MDR-PA isolates were obtained from patients at Songklanagarind Hospital, in southern Thailand, during January 2008-March 2011. Antimicrobial susceptibilities to amikacin (AK), ceftazidime (CAZ), ciprofloxacin (CIP), imipenem (IMP) and colistin (CO) were tested by standard disk diffusion method. The antimicrobial susceptibility to colistin and the MIC were determined with the E-test. The MDR-PA isolates were susceptible to ceftazidime, ciprofloxacin, amikacin and imipenem in 1, 5, 11 and 32%, respectively. There were 5 antimicrobial resistance patterns of MDR-PA: AK-CAZ-CIP-IMP (50%), AK-CAZ-CIP (32%), CAZ-CIP-IMP (11%), AK-CAZ-IMP (6%) and AK-CIP-IMP (1%). Colistin had good efficacy against MDR-PA (98% susceptibility rate). The MIC50 and MIC90 for colistin were 1.0 and 1.5 jig/ml, respectively. Only 2 MDR-PA isolates were resistant to colistin with the MICs of 3 and 12 microg/ml, respectively. The majority of MDR-PA isolates remained susceptible to colistin; therefore, colistin is a good option for treatment of MDR-PA.

Outcome of dengue hemorrhagic fever-caused acute kidney injury in Thai children.

OBJECTIVES: To examine the outcome of acute kidney injury (AKI) in children with dengue hemorrhagic fever (DHF), the cause(s) of AKI, and the risk of AKI and fatality. STUDY DESIGN: The medical records of patients age <15 years during 1989 to 2007 were reviewed. DHF-caused AKI and patients with DHF with no AKI were matched 1:2 by age. RESULTS: DHF-caused AKI was clinically estimated to be 0.9% (25/2893) of admissions, with a high mortality rate of 64.0%. Risk factors of AKI were DHF grade IV and obesity (odds ratio, 16.9; 95% CI, 4.2 to 68.5, and odds ratio, 6.3; 95% CI, 1.4 to 28.8, respectively). Respiratory failure, hepatic failure, and massive bleeding were complications found in 80.0%, 96.0%, and 84.0% of cases with AKI, respectively. Fatality was more likely in cases with DHF grade IV, oliguric AKI, respiratory failure, or prolongation of prothrombin or activated partial thromboplastin time more than twice that of reference specimens. Among the survivors, none had chronic kidney disease, and serum creatinine levels returned to normal in 32 (1 to 48) days. CONCLUSIONS: Patients with DHF and AKI had a high mortality rate, although those who survived had a full return to normal function within 1 month. DHF grade IV and obesity were the major risk factors of AKI.

Clinical outcome of febrile neutropenia in children with cancer using ceftazidime and aminoglycosides.

To determine treatment outcome using ceftazidime-aminoglycosides in febrile neutropenic children with cancer, the authors conducted a prospective cohort study in 216 episodes. Early and complete responses to antibiotics were 108/216 (50.0%) and 133/216 (61.6%) episodes, respectively. Death, a modification of antibiotic(s), and resistance to ceftazidime were 2/118 (1.7%), 73/216 (33.8%), and 4/216 (1.9%) episodes, respectively. Primary bacteremia and emerging bacteremia during treatment were 20/216 (9.3%) and 5/216 (2.3%) episodes. Ceftazidime-aminoglycosides was found to be a reasonable initial treatment of febrile neutropenia in the authors' institution. Imipenem is considered in patients who have clinical sepsis and who fail to respond to initial treatment.

In vitro activity of fosfomycin-gentamicin, fosfomycin-ceftazidime, fosfomycin-imipenem and ceftazidime-gentamicin combinations against ceftazidime-resistant Pseudomonas aeruginosa.

The effects of antimicrobial combinations against ceftazidime-resistant Pseudomonas aeruginosa strains isolated from hospitalized patients were investigated. Using the checkerboard titration method, combination of fosfomycin-gentamicin, fosfomycin-ceftazidime, fosfomycin-imipenem and ceftazidime-gentamicin was synergistic against 4, 11, 38 and 39% of 22, 18, 29 and 18 strains tested respectively and additive effect of the combinations against the strains tested was 41, 33, 14 and 44%, respectively. Antagonistic effects against the isolates were noted when fosfomycin was combined with gentamicin (27%), ceftazidime (22%) and imipenem (7%). No antagonistic effect was observed in the ceftazidime-gentamicin combination.

Dengue myocarditis.

We report a 13-year-old boy who developed bradycardia and hypotension a day after recovery from dengue hemorrhagic fever. His electrocardiogram, during the bradycardia, showed a junctional rhythm with a rate of 50 beats/minute. This is the first reported case of sinus node dysfunction following dengue infection.

Perinatal dengue infection: a case report and review of literature.

A case of vertical transmission of dengue infection in the perinatal period is reported. The mother, a term pregnancy, had acute dengue the day before admission. The infant was born at term and developed fever on the fifth day of life which lasted for 5 days. No bleeding or plasma leakage was detected during the course of fever in infant or mother. A liver function test showed elevated SGOT and SGPT in the infant. The infant developed a convalescent rash on day 5 of the fever. The diagnosis of secondary dengue hemorrhagic fever in the mother was confirmed by serology and primary dengue infection in the infant was confirmed by serology and serotyped as dengue type 2 by PCR. The clinical course and management of mothers and infants with perinatal dengue infection are reviewed.