Pornpimol Pruekprasert

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.

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.

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.

Non-fatal septicaemic {itNocardia asteroides} in a girl with systemic lupus erythematosus

Awareness is drawn to the possibility of nocardial infection in children with systemic lupus erythematosus.

Congenital Cytomegalovirus Infection Presenting with Isolated Secretory Diarrhoea Mimicking a Congenital Diarrhoeal Disorder

To the best of our knowledge, a congenital cytomegalovirus (CMV) infection presenting with only secretory diarrhoeal symptoms without other apparent clinical features of CMV infection has never been reported. We describe an infant with congenital CMV infection who presented with an atypical manifestation of isolated severe secretory diarrhoea, mimicking a congenital diarrhoeal disorder. A 5-week-old male breastfed infant had a history of passing 8–10 profuse watery stools daily beginning at the age of 1 week. The patient was a full-term neonate with a birthweight of 3500 g through a vaginal delivery without complications. The maternal antenatal history was normal. On admission, the patient was dehydrated. His weight was 4 kg (P 25) and head circumference was 39 cm (P 90). The physical examination revealed no skin rash and no hepatosplenomegaly. A stool examination showed watery stool with a few white and red blood cells. Stool cultures for enteric pathogens and stool testing for Clostridium difficile toxin A and an enzyme immunoassay for rotavirus were all negative. Neonatal human immunodeficiency virus infection and bacterial septicaemia were excluded due to negative results from a serologic test and haemoculture, respectively. The patient passed a large amount of watery stool (350–400 mL/day) during fasting and an electrolytes assay showed Na 131 mmol/L, K 5.8 mmol/L, Cl 118 mmol/L, HCO3 − 10 mmol/L and osmotic gap 16 mOsm/kg. All results were consistent with secretory diarrhoea. The complete blood count, urinalysis, liver function tests, C-reactive protein and urine vanillylmandelic acid were all normal. An oesophagogastroduodenoscopy revealed swelling duodenal mucosa with scattered hyperaemic lesions. A colonoscopy showed generalised swelling, scattered erythematous epithelium with haemorrhage and erosions of the colonic mucosa from the rectum up to the caecum. Biopsies taken from the duodenal and colonic mucosa showed significant inflammatory cell infiltrations in the lamina propria with intranuclear and cytoplasmic inclusions of the stromal and endothelial cells that was suggestive of CMV infection. Immunohistochemical staining of the inclusions for CMV was positive. Further investigations to confirm a CMV infection showed positive results for anti-CMV Ig M and 9650 copies/mL of CMV viral load in the serum. An ophthalmologic examination for chorioretinitis was negative. Computer tomography of the brain showed evidence of congenital CMV infection during the fetal period by the finding of calcification of the bilateral basal ganglia. The patient was treated with intravenous ganciclovir followed by oral valganciclovir until a total of 6 months of anti-CMV therapy was completed. He had an uneventful recovery. An auditory brain-stem response hearing examination at 9 months of age was normal. At the most recent follow-up at the age of 1 year, he had good neurodevelopment and normal growth. We believe that a severe inflammation of the small intestine by a heavy CMV infection was involved in the pathogenesis of secretory diarrhoea in our patient. The mechanism was excessive stimulation of Cl secretion by the release of TNF and IL-6 from the CMV-infected monocytes and macrophages during innate inflammatory response. In spite of its rarity, enterocolitis due to congenital CMV infection should be recognised as a possible cause in the early onset of secretory diarrhoea in neonates because this disease can be completely cured with anti-CMV therapy.