Immunogenicity and reactogenicity of fractional, heterologous primary COVID-19 vaccination schedules with BNT162b2 boosters in 5-11-year-old Thai children: A multicenter, prospective, double-blind, randomized control trial.

OBJECTIVE: To evaluate immunogenicity and safety of heterologous COVID-19 primary vaccination regimens of CoronaVac with fractional and standard BNT162b2 dosages in 5-11-year-old Thai children. METHODS: This prospective, multicenter, double-blind, randomized control trial divided participants 1:1:1:1 to receive a second dose of either standard (10-µg) or half-dose (5-µg) BNT162b2 vaccines as follows: CoronaVac/10-µg-BNT162b2 (Group 1), CoronaVac/5-µg-BNT162b2 (Group 2), 10-µg-BNT162b2/10-µg-BNT162b2 (Group 3), or 10-µg-BNT162b2/5-µg-BNT162b2 (Group 4). A subset of participants from each arm received 10-µg-BNT162b2 booster (third) doses 16 weeks after their second vaccination. Humoral and cellular immunogenicity were assessed and adverse events (AEs) digitally self-reported. RESULTS: Of 553 enrolled participants, 50 % were male, the median (interquartile range) age was 8.65 (7.00, 10.00) years, and a majority (91 %) had normal weight-for-height. All participants exhibited similarly robust neutralizing antibodies (NAb) against the ancestral Wuhan strain two weeks after the second vaccination, with titers highest in Group 1 (737.60, 95% CI [654.80, 830.88]), followed by Groups 3 (630.42, 95% CI [555.50, 715.45]), 2 (593.98, 95% CI [506.02, 697.23]), and 4 (451.79, 95% CI [388.62, 525.23]), as well as 56.01 % and 49.68 % seroconversion for BA.1 and BA.5, respectively. Half-dose BNT162b2 as a second dose induced significantly lower NAb titers compared to their respective full-dose regimens (p = 0.03 for Groups 1 vs 2 and p < 0.001 for Groups 3 vs 4). 77.71 % of participants developed SARS-CoV-2 ancestral spike protein-specific T-cell responses two weeks after the second vaccination. This was similar across arms. Booster doses generated NAb titers 5.69-11.51-folds higher than the second vaccination against BA.1. AEs were similar across arms, all mild or moderate, and fully resolved 2-3 days thereafter. CONCLUSION: Standard and fractional heterologous regimens of CoronaVac-BNT162b2 induced similar or higher humoral immunity than homologous BNT162b2 and represent alternative vaccine regimens for children. These findings are highly relevant in settings concurrently using both vaccines.

Outcomes among Thai children with risk conditions hospitalized for pneumococcal disease (invasive or non-bacteraemic pneumonia): A multi-centre, observational study.

Objective: To describe the risk condition status and clinical outcomes among Thai children hospitalized with pneumococcal disease. Methods: In this retrospective analysis, children with invasive pneumococcal disease (IPD) or x-ray-confirmed non-bacteraemic pneumococcal pneumonia (NBPP) were identified from nine hospitals in Thailand between 2010 and 2019. Data on risk factors and outcomes were extracted from medical records. Results: In total, 413 cases were identified: 319 IPD and 94 NBPP. Overall, 133 (32.2%) patients were admitted to intensive care units and 11/406 (2.7%) died. Twenty-seven percent of IPD cases had at-risk conditions and 15% had high-risk conditions. Most IPD cases (32.9%) occurred in children aged 2-4 years, and most NBPP cases (28.7%) occurred in infants aged 0-11 months. Of 51 Streptococcus pneumoniae isolates collected, 41 (80%) were pneumococcal 13-valent conjugate vaccine serotypes. Only 5.1% of children had received a pneumococcal vaccine. Conclusions: Most children with IPD and NBPP did not have high-risk or at-risk conditions, while 42% had at-risk or high-risk conditions for pneumococcal disease. Very few children in the cohort had received any type of pneumococcal vaccine. Increasing the availability of pneumococcal conjugate vaccines should be considered to reduce the burden of pneumococcal disease among children in Thailand.

Using procalcitonin levels to predict infection and reduce unnecessary antibiotic usage in febrile children aged 3-36 months.

INTRODUCTION: High risk features including body temperature (BT) ≥ 39 °C, inactive appearance, white blood cells (WBC) ≥ 15,000 cells/mm3, or absolute band count (ABC) ≥ 1,500 cells/mm3 have low sensitivity and negative predictive value (NPV) to discriminate between bacterial and viral infections, leading to overuse of antibiotics. We aimed to determine whether procalcitonin (PCT) level ≥ 0.5 ng/mL can differentiate bacterial from viral infections. METHODOLOGY: The medical data of children aged 3 to 36 months who presented with fever without localizing signs or having initially undetermined cause of respiratory tract infection and/or non-mucus bloody diarrhea for 1 to 7 days and were hospitalized between January 2017 and December 2018 with one of the high-risk features were recorded. Children with an immunocompromised condition, who had previously received antibiotics, and/or had clinical sepsis were excluded. RESULTS: Non-serious bacterial infection (SBI) and SBI (occult bacteremia) were found in 17.2% and 4.5%, respectively. The proportions of children with high-risk features were not significantly different between children with and without bacterial infection, except for absolute band count which was significantly higher in the bacterial infection group (419 cells/mm3, IQR [0, 1429]) than the non-bacterial group (76 cells/mm3, IQR [0,455]). A PCT level ≥ 0.5 ng/mL had the highest sensitivity and NPV (100%, 100%, respectively) to predict bacterial infection when compared with the other high-risk features. CONCLUSIONS: Antibiotics can be safely withheld while waiting for hemoculture in acute febrile children with one of the high-risk features of bacterial infection with PCT level < 0.5 ng/mL.

Safety and Immunogenicity of a New Inactivated Polio Vaccine Made From Sabin Strains: A Randomized, Double-Blind, Active-Controlled, Phase 2/3 Seamless Study.

BACKGROUND: A new inactivated polio vaccine made from Sabin strains (sIPV) was developed as part of the global polio eradication initiative. METHODS: This randomized, double-blind, active-controlled, phase 2/3 seamless study was conducted in 2 stages. Healthy infants aged 6 weeks were randomly assigned to receive 3 doses of 1 of 4 study vaccines at 6, 10, and 14 weeks of age (336 received low-, middle-, or high-dose sIPV, or conventional IPV [cIPV] in stage I, and 1086 received lot A, B, or C of the selected sIPV dose, or cIPV in stage II). The primary outcome was the seroconversion rate 4 weeks after the third vaccination. RESULTS: In stage I, low-dose sIPV was selected as the optimal dose. In stage II, consistency among the 3 manufacturing lots of sIPV was demonstrated. The seroconversion rates for Sabin and wild strains of the 3 serotypes after the 3-dose primary series were 95.8% to 99.2% in the lot-combined sIPV group and 94.8% to 100% in the cIPV group, proving the noninferiority of sIPV compared to cIPV. No notable safety risks associated with sIPV were observed. CONCLUSIONS: Low-dose sIPV administered as a 3-dose vaccination was safe and immunogenic compared to cIPV. CLINICAL TRIALS REGISTRATION: NCT03169725.

Mortality Rates of Severe Dengue Viral Infection Before and After Implementation of a Revised Guideline for Severe Dengue.

OBJECTIVES: To compare the mortality rate of severe dengue (SD) before and after implementation of a revised SD guideline. METHODS: Medical records of SD patients <15 years of age hospitalized during 1998-2020 were reviewed. The revised SD guidelines were implemented in 2016, including intensive monitoring of vital signs and intra-abdominal pressure, the release of intra-abdominal pressure in cases of abdominal compartment syndrome (ACS) and the use of N-acetyl cysteine in cases of acute liver failure. RESULTS: On initial admission, organ failure including severe bleeding, acute respiratory failure, acute kidney injury and acute liver failure was not significantly different between 78 and 23 patients treated in the pre- and postrevised guideline periods, respectively. After hospitalization, the proportions of patients who developed profound shock (68.8% vs. 41.2%), multiorgan failures (60.4% vs. 73.3%), ACS (37.2% vs. 26.1%) and fatal outcome (33.3% vs. 13.0%) were also not significantly different between the pre- and postrevised guideline periods, respectively. In subgroup analysis, the mortality rates in patients with multiorgan failure (44.1% vs. 15.8%), acute respiratory failure and active bleeding (78.1% vs. 37.5%) and ACS (82.8% vs. 33.3%), respectively, were significantly higher in the pre- than the postrevised guideline periods. The durations of time before the liver function tests returned to normal levels, and the mortality rates in acute liver failure patients treated with and without N-acetyl cysteine were not significantly different. CONCLUSIONS: Although following the revised guidelines could not prevent organ failure, the mortality rates in patients with multiorgan failure and/or ACS decreased significantly when following the revised guidelines.

Comparing Treatment Outcomes between Confirmed and Non-Confirmed Childhood TB Cases: Study from a Major Tertiary Center in Thailand.

BACKGROUND: Tuberculosis (TB) in children is challenging to diagnose due to its non-specific symptoms and difficulties in obtaining confirmatory laboratory results. This study aimed to compare the treatment outcomes of confirmed and non-confirmed TB in children. METHODS: The medical records of children aged ≤ 15 years diagnosed with TB at Songklanagarind Hospital from January 2007 to December 2018 were examined. The TB cases were classified into three groups, confirmed cases (positive culture and/or polymerase chain reaction), probable cases (positive histopathological and/or acid-fast bacilli results) and presumptive cases (clinical manifestations and imaging findings compatible with TB and good response to anti-TB drugs but without microbiological confirmation). RESULTS: Of 177 children, 66 (37.3%) had a confirmed diagnosis, 57 (32.2%) a probable diagnosis, and 54 (30.5%) a presumptive diagnosis. The successful treatment rates of the confirmed, probable and presumptive TB groups were 80.3%, 87.7% and 92.6%, respectively (p = 0.21). Of the 54 presumptive cases, a history of household contact with TB led to a diagnosis of asymptomatic pulmonary TB in 10 (18.5%) cases. Patients with a presumptive diagnosis were less likely to have disseminated and/or miliary TB (1.9% vs. 7.0% of probable vs. 22.7% of confirmed, p < 0.01). CONCLUSIONS: Only one-third of the study patients had a confirmed TB diagnosis. The successful treatment and mortality rates did not significantly differ among the three groups. To increase the detection rate of early diagnosis of childhood TB, physicians should perform active TB contact investigations in household members of the index case.

Using Clinical Profiles and Complete Blood Counts to Differentiate Causes of Acute Febrile Illness during the 2009-11 Outbreak of Typhoid and Chikungunya in a Dengue Endemic Area.

BACKGROUND AND AIMS: After the 2009-11 outbreak of typhoid and chikungunya (CHIK) in Thailand, an effort was made to use complete blood counts and clinical profiles to differentiate these diseases to facilitate earlier specific treatment. METHODS: Patients aged 2-15 years having fever on first visit ≤3 days without localizing signs were enrolled retrospectively. Typhoid fever was confirmed by hemoculture, dengue by nonstructural protein-1 or polymerase chain reaction (PCR), and CHIK by PCR. Febrile children with negative results for these infections were classified as other acute febrile illness (AFI). RESULTS: Of the 264 cases, 56, 164, 25 and 19 had typhoid fever, dengue viral infection (DVI), CHIK and other AFI, respectively. Arthralgia had sensitivity, specificity, positive predictive value (PPV) and negative predictive value of 0.96, 0.97, 0.80 and 0.99, respectively, to differentiate CHIK from the others. After excluding CHIK by arthralgia, the PPV of the WHO 1997 and 2009 criteria for DVI increased from 0.65 and 0.73 to 0.95 and 0.84, respectively. Children with one of myalgia, headache or leukopenia had sensitivity of 0.84, specificity of 0.76 and PPV of 0.92 to differentiate DVI from typhoid and other AFIs. Patients with one of abdominal pain, diarrhea or body temperature >39.5°C were more likely to have typhoid fever than another AFI with PPV of 0.90. CONCLUSION: Using this flow chart can help direct physicians to perform more specific tests to confirm the diagnosis and provide more specific treatment. Nevertheless, clinical follow-up is the most important tool in unknown causes of febrile illness.

Hepatic/splenic abscess and/or skin and soft tissue infection as predictors of melioidosis in children.

INTRODUCTION: Melioidosis can have multiple organ involvement which can then mimic other infections. The aim of this study was to determine if there are any factors significantly associated with melioidosis which can inform diagnostic evaluations before receiving the results of confirming laboratory testing. METHODOLOGY: The charts of patients aged < 16 years admitted to Songklanagarind Hospital during 2002-2014 with a clinical presentation suspicious of melioidosis were reviewed. RESULTS: Of the 145 suspected cases, 27 patients had a confirmed diagnosis of melioidosis by either serology and/or culture. The melioidosis group had a higher proportion of patients with liver or splenic abscess (44.4% vs. 11.9%, p < 0.01) and were less likely to have splenomegaly by physical examination (3.7% vs. 22.9%, p = 0.02) than patients without melioidosis. Logistic regression analysis found that patients suspected of melioidosis who had (a) hepatic abscess or (b) splenic abscess or (c) skin or soft tissue infection were more likely to have melioidosis with likelihood ratios of 5.6, 4.0, and 2.2 respectively, and specificities of 0.94, 0.89, and 0.68 respectively. Suspected patients who did not have hepatic abscess, splenic abscess, or soft tissue infection were unlikely to have melioidosis with negative predictive value of 0.90. CONCLUSION: patients who have clinically suspected melioidosis without skin or soft tissue infection should have hepatic-splenic ultrasonography performed, and suspected patients who have one of these 3 findings should be treated initially as melioidosis while waiting for culture or serologic test results.

Does ciprofloxacin prophylaxis during chemotherapy induce intestinal microflora resistance to ceftazidime in children with cancer?

To determine the susceptibility and minimal inhibitory concentrations (MIC) of ceftazidime, the commonly used empirical antibiotic in patients with febrile neutropenia, in Escherichia coli and Klebsiella pneumoniae isolated from the intestinal microflora of pediatric patients with cancer, who received ciprofloxacin prophylaxis during chemotherapy, children younger than 18 years with acute lymphoblastic leukemia or lymphoma scheduled to undergo chemotherapy were randomized to receive oral ciprofloxacin 20 mg/kg/day or placebo from the beginning of their chemotherapy. Rectal swab cultures were taken before (R0) and at 1 (R1), 2 (R2), and 3 (R3) weeks during the intervention. The antimicrobial susceptibilities and MICs of ceftazidime and ciprofloxacin were determined via the E test. Of the total 87 patients enrolled, 44 received ciprofloxacin and 43 placebo. A total of 350 isolates were obtained, 62, 49, 46 and 22 from the ciprofloxacin group and 68, 54, 38 and 11 from the placebo group at R0, R1, R2 and R3, respectively. The percentages of ceftazidime susceptibility did not show significantly greater decreases from R0 to R1-R3 in the ciprofloxacin group compared to the placebo group. The MIC50s of ceftazidime showed significantly greater increases after ciprofloxacin prophylaxis during R1-R3 compared to R0 in the intervention group compared to the placebo group (R0, 0.12 vs. 0.12; R1, 0.19 vs. 0.12; R2, 0.19 vs. 0.12 and R3, 0.38 vs. 0.09 µg/mL, respectively). Due to the increasing MIC50 of ceftazidime over time after ciprofloxacin prophylaxis, the use of ceftazidime in patients who have previously had ciprofloxacin prophylaxis needs to be closely monitored.

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.

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.

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.

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.

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.

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.

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/mm(3) 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/mm(3) or specific antigen testing (if available) can be helpful in differentiating CHIK from DVI.

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.

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.

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.