Kamolwish Laoprasopwattana

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.

Differential diagnosis of Chikungunya, dengue viral infection and other acute febrile illnesses in children.

Background: Clinical manifestations of chikungunya (CHIK) are similar to those of dengue. It would be useful to be able to identify clinical manifestations that could reliably help to differentiate CHIK from dengue and other acute febrile illnesses during a CHIK outbreak in a dengue-endemic area. Methods: A prospective cohort study was conducted between April and July 2009 in children aged 1 month to 15 years who lived in a CHIK outbreak area in southern Thailand and who had fever <7 days with arthralgia/arthritis, myalgia or rash. CHIK was confirmed by real-time polymerase chain reaction or the indirect immunofluorescence test. Results: Fifty patients were suspected of having CHIK, of whom 32 were confirmed, 1 had coinfection with dengue viral infection (DVI), 10 had dengue alone and 7 had an acute febrile illness. The specificity and positive predictive value of fever and arthralgia together to diagnose CHIK were 47.1% and 74.2%, and the corresponding values of the standard clinical triad (fever, arthralgia, rash) were 70.6% and 83.3%, respectively. Fever ⩽2 days, skin rash during fever and white blood cell count ≥ 5000 cells/mm3 were independently and significantly associated with CHIK in comparison with DVI and acute febrile illnesses, with relative risk ratios (95% confidence intervals) of 10.4 (0.9–116) and 13.7 (1.3–145), 13.8 (1.2–164) and 14.8 (1.6–168), and 18.3 (1.7–194) and 1.8 (0.1–20.6), respectively. Conclusions: During a CHIK outbreak in a DVI-endemic area, overdiagnosis of CHIK was common. Skin rash during fever and white blood cell count ≥ 5000 cells/mm3 or specific antigen testing (if available) can be helpful in differentiating CHIK from DVI.

Ciprofloxacin reduces occurrence of fever in children with acute leukemia who develop neutropenia during chemotherapy.

Background: Fluoroquinolones reduce occurrence of fever in adult cancer patients who develop neutropenia, but there has been no randomized controlled trial in children, and there are only a few studies considering resistance in intestinal floral after ciprofloxacin has been used. Methods: Children younger than 18 years with acute lymphoblastic leukemia or lymphoma scheduled to undergo chemotherapy were randomized to receive oral ciprofloxacin 20mg/kg/day or placebo from the beginning of their chemotherapy. Rectal swab cultures were taken before and at 1 and/or 2 weeks after the intervention. Results: Of the total of 95 patients, 45 and 50 patients received ciprofloxacin and placebo, respectively. Of the 71 patients who developed neutropenia, the proportion of children who developed fever was significantly lower in the ciprofloxacin group than in the placebo group (17/34 [50.0%] versus 27/37 [73.0%]; absolute difference in risk, –23.0%; 95% confidence interval: –45.0% to –0.9%; P = 0.046). Ciprofloxacin significantly reduced the occurrence of febrile episodes in patients with acute lymphoblastic leukemia in the induction phase of chemotherapy, but not in patients with lymphoma or in the consolidation phase of chemotherapy. Adverse effects were not different between the groups. After intervention, the percentages of Escherichia coli and Klebsiella pneumoniae susceptible to ciprofloxacin were significantly lower in the ciprofloxacin group. Conclusion: Ciprofloxacin can prevent fever in neutropenic patients with acute lymphoblastic leukemia during the induction phase of chemotherapy with good tolerance and no serious side effects. Due to the selective pressure of intestinal flora resistance to ciprofloxacin, the long-term effectiveness needs further investigation.

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.

Fatal infection in children with lupus nephritis treated with intravenous cyclophosphamide

A knowledge of the causes and risk factors of fatal infection in childhood lupus nephritis (LN) patients treated with intravenous cyclophosphamide (IVCY) is important to enable optimal treatment. During an 11-year period (1996–2007), severe infection cases occurred in 31/84 (36.9%) patients with 64 infection episodes in our central referral institution in southern Thailand. Fatal infections occurred in 13/31 (41.9%) patients, most (11/13, 84.6%) during the first infective episode. The major causative organisms of the fatal infections were fungus and Gram-negative bacilli. Fatal infections were more likely to occur in patients with a prior history of treatment with pulse methylprednisolone and in patients with more active LN, as evidenced by the higher proteinuria and serum creatinine levels and lower hemoglobin and lymphocyte counts in this group than in patients with non-fatal infections. Multivariate analysis indicated that factors associated with fatal infection were prior treatment with pulse methylprednisolone [odds ratio (OR) 11.2, 95% confidence interval (CI) 1.9–61.0], renal failure (OR 5.9, 95% CI 1.0–34.8), and fungal infection (OR 23.9, 95% CI 1.9–298.2). Cases of active LN treated with IVCY and pulse methylprednisolone who later develop severe infection that fails to respond to antibiotics should be carefully investigated for fungal infection.

Is zinc concentration in toxic phase plasma related to dengue severity and level of transaminases

Objective To determine the relationship between plasma zinc values and the severity of dengue viral infection (DVI) and DVI-caused hepatitis. Methods A prospective cohort study was conducted during 2008–2010 in hospitalized children aged <15 years confirmed with DVI. Complete blood count, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and zinc values (mcg/dL) were determined twice: first during the toxic phase (Zn1) and secondly two weeks after recovery (Zn2). Results 39 patients were enrolled with a mean age of 9.7±3.7 years, and 15/39 diagnosed with dengue shock syndrome (DSS). Zn1 values were lower than Zn2 values [median (IQR): 46.0 (37.0, 58.0) vs 65.0 (58.0, 81.0) mcg/dL, respectively, p <0.01]. Zn1 but not Zn2 values had a negative correlation with AST and ALT (rs = −0.33, p = 0.04 and rs = −0.31, p = 0.05, respectively). Patients with DSS had lower Zn1 but not Zn2 values compared with non-DSS patients [median (IQR) Zn1, 38.0 (30.0, 48.0) vs 52.5 (41.2, 58.7), p = 0.02; Zn2, 61.0 (56.0, 88.0) vs 65.0 (59.5, 77.5), respectively, p = 0.76]. Zn1 values showed a decreasing trend across increasing dengue severity groups (p = 0.02). Age <5 years and DVI-associated diarrhea were associated with low Zn1. Conclusion Children who had a higher grade of dengue disease severity and liver cell injury had lower Zn1 values. Low Zn1 values were probably caused by loss from diarrhea and from zinc translocating to liver cells.

Typhoid Outbreak in Songkhla, Thailand 2009–2011: Clinical Outcomes, Susceptibility Patterns, and Reliability of Serology Tests

Objective To determine the clinical manifestations and outcomes, the reliability of Salmonella enterica serotype Typhi (S ser. Typhi) IgM and IgG rapid tests, and the susceptibility patterns and the response to treatment during the 2009–2011 typhoid outbreak in Songkhla province in Thailand. Method The medical records of children aged <15 years with S ser. Typhi bacteremia were analysed. The efficacy of the typhoid IgM and IgG rapid tests and susceptibility of the S ser. Typhi to the current main antibiotics used for typhoid (amoxicillin, ampicillin, cefotaxime, ceftriaxone, co-trimoxazole, and ciprofloxacin), were evaluated. Results S ser. Typhi bacteremia was found in 368 patients, and all isolated strains were susceptible to all 6 antimicrobials tested. Most of the patients were treated with ciprofloxacin for 7–14 days. The median time (IQR) of fever before treatment and duration of fever after treatment were 5 (4, 7) days and 4 (3, 5) days, respectively. Complications of ascites, lower respiratory symptoms, anemia (Hct <30%), and ileal perforation were found in 7, 7, 22, and 1 patients, respectively. None of the patients had recurrent infection or died. The sensitivities of the typhoid IgM and IgG tests were 58.3% and 25.6% respectively, and specificities were 74.1% and 50.5%, respectively. Conclusion Most of the patients were diagnosed at an early stage and treated with a good outcome. All S ser. Typhi strains were susceptible to standard first line antibiotic typhoid treatment. The typhoid IgM and IgG rapid tests had low sensitivity and moderate specificity.

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.