Control of blood pressure in hypertensive children and adolescents assessed by ambulatory blood pressure monitoring.

BACKGROUND: There have been few studies evaluating the control of hypertension (HT) in children. This study aimed to assess the control of HT using ambulatory blood pressure monitoring (ABPM) and to compare the parameters between the uncontrolled HT and controlled HT groups. METHODS: Hypertensive patients aged ≥ 5 years who underwent ABPM to assess the control of HT were enrolled. Demographics, office blood pressure (BP), ABPM, and echocardiographic data were collected. Controlled HT was defined using a BP goal recommended by the 2016 European Society of Hypertension guidelines. RESULTS: There were 108 patients (64.8% males) with a mean age of 14.3 years and 51.9% had primary HT. Controlled HT was detected in 41.1% and 33.3% by office BP and ABPM, respectively. Based on ABPM, there was a greater prevalence of controlled HT in the primary HT than the secondary HT group (44.6% vs. 21.2%, P = 0.01). In the primary HT group, BMI z-score at the last follow-up had a significant decrease in the controlled HT than the uncontrolled HT group (-0.39 vs. 0.01, P = 0.032). Primary HT was negatively associated with uncontrolled HT by ABPM. In addition, ABPM showed greater sensitivity (77.8% vs. 55.8%) and negative predictive value (80.9% vs. 70.8%) to predict LVH than those of office BP measurement. CONCLUSION: Only one-third of patients achieved the BP goal by ABPM and most were in the primary HT group. Weight reduction is an important measure of BP control in patients with primary HT to attenuate the risk of LVH.

Inadequate blood pressure control demonstrated by ambulatory blood pressure monitoring in pediatric renal transplant recipients.

BACKGROUND: Adequate BP control in RT recipients should not rely only by normal office BP but also on normal 24-hour BP. This study aims to assess adequacy of BP control by ABPM and to assess ABPM parameters associated with LVMI in pediatric RT recipients. MATERIALS AND METHODS: Patients aged 5-20 years who have been followed after RT were enrolled. Demographic data and BP assessed by office and ABPM were collected. Echocardiography was performed to detect LVMI. RESULTS: Thirty RT recipients (18 males) with median age of 15 years (IQR 13-18.5) were included. Among 23 patients who were taking antihypertensive drugs, uncontrolled hypertension was detected in 34.8% and 78.3% by office BP measurement and ABPM, respectively. Thus, the difference in prevalence of uncontrolled hypertension observed by ABPM versus office BP was 43.5%. Those seven patients who were not taking antihypertensive drugs because of normal office BP, four patients (57.1%) had masked hypertension and one patient had elevated BP. Fifteen patients have progression of LVH after RT. Multivariate analysis revealed that age (OR 1.369, 95%CI 0.985-1.904, P-value = 0.062) had a trend to be associated with progression of LVH. Moreover, nighttime systolic BP z-score was significantly correlated with LVMI (r = 0.551, P-value = 0.002). CONCLUSION: The difference in prevalence of uncontrolled hypertension uncovered by ABPM was 43.5%. Nighttime SBP z-score was significantly correlated with LVMI.

Differences in activation and tissue homing markers of natural killer cell subsets during acute dengue infection.

Dengue virus (DENV) infection is considered one of the most important mosquito-borne diseases. It causes a spectrum of illness that could be due to qualitative and/or quantitative difference(s) of the natural killer (NK) cell responses during acute DENV infection. This view prompted us to perform a detailed phenotypic comparative characterization of NK cell subsets from DENV-infected patients with dengue fever (DF), patients with dengue haemorrhagic fever (DHF) and healthy controls. The activation/differentiation molecules, CD69 and CD57 and a variety of tissue homing molecules were analysed on the CD56hi CD16- and CD56lo CD16+ NK cells. Although there was no increase in the frequency of the total NK cells during DENV infection compared with the healthy individuals, there was a significant increase in the frequency of the CD56hi CD16- subset and the frequency of CD69 expression by both NK cell subsets during the febrile phase of infection. We also found an increase in the frequencies of cells expressing CD69 and CD57 in the CD56lo CD16+ subset compared with those in the CD56hi CD16- subset. Moreover, although the CD56lo CD16+ subset contained a high frequency of cells expressing skin-homing markers, the CD56hi CD16- subset contained a high frequency of cells expressing bone marrow and lymph node trafficking markers. Interestingly, no differences of these NK cell subsets were noted in samples from patients with DF versus those with DHF. These findings suggest that activation and differentiation and the patterns of tissue homing molecules of the two major NK cell subsets are different and that these might play a critical role in the immune response against acute DENV infection.

B cell subset alteration and the expression of tissue homing molecules in dengue infected patients.

BACKGROUND: B cells play an essential role during dengue viral infection. While a major expansion of antibody secreting cells (ASCs) was observed, the importance of these increased frequencies of ASCs remains unclear. The alteration of B cell subsets may result from the expression of tissue specific homing molecules leading to their mobilization and distribution to different target organs during acute dengue viral infection. METHODS: In this study, whole blood samples were obtained from thirty pediatric dengue-infected patients and ten healthy children and then stained with fluorochrome-conjugated monoclonal antibodies against CD3, CD14, CD19, CD20, CD21, CD27, CD38, CD45, CD138 and homing molecules of interest before analyzed by polychromatic flow cytometry. B cell subsets were characterized throughout acute infection period. RESULTS: Data shows that there were no detectable differences in frequencies of resting, activated and tissue memory cells, whereas the frequency of ASCs was significantly increased and associated with the lower frequency of naïve cells. These results were found from patients with both dengue fever and dengue hemorrhagic fever, suggesting that such change or alteration of B cells was not associated with disease severity. Moreover, several homing molecules (e.g., CXCR3 and CCR2) were found in ASCs, indicating that ASCs may distribute to inflamed tissues and various organs. CONCLUSIONS: Findings from this study provide insight into B cell subset distribution. Furthermore, organ mobilization according to homing molecule expression on different B cell subsets during the course of dengue viral infection also suggests they are distributed to inflamed tissues and various organs.

Myocardial performance index in active and inactive paediatric systemic lupus erythematosus.

OBJECTIVES: To evaluate cardiac structure and function in paediatric SLE patients without clinical evidence of cardiovascular disease in active and inactive diseases. METHODS: Patients aged ≤20 years who fulfilled the diagnostic criteria of active SLE underwent transthoracic echocardiography to evaluate cardiac structure and function, and were then followed up echocardiographically every 3-4 months until SLE disease was inactive. Patients with heart failure, myocarditis, pericarditis, endocarditis, coronary artery disease, or abnormal structural heart disease were excluded. RESULTS: Twenty-six active SLE patients, mean age 13.2±3.3 years, of whom 20 were female (77%), were enrolled. Most patients had cardiac abnormalities especially LV global dysfunction assessed by left ventricular myocardial performance index (LV MPI). LV MPI by conventional method, by tissue Doppler imaging (TDI) at medial and lateral mitral valve annulus were significantly decreased when compared to LV MPI in patients with inactive disease (0.44±0.14 vs. 0.30±0.05, 0.52±0.09 vs. 0.36±0.04, and 0.51±0.09 vs. 0.35±0.05, p<0.001). Using receiver operating characteristic, LV MPI cut-off at 0.37, 0.40, and 0.40 by conventional, medial TDI, lateral TDI had sensitivity and specificity of 90% and 84%, 90% and 96%, 90% and100%, respectively. CONCLUSIONS: Left ventricular global dysfunction was found to be common in paediatric patients with active SLE. LV MPI by TDI might be useful to diagnose active SLE in paediatric patients.

Unusual cause of anemia in a child with end-stage renal disease: Questions.

This is the case of a 5-year-old girl diagnosed with end-stage renal disease due to bilateral renal hypoplasia who developed anemia of unknown cause.

High Anti-Dengue Virus Activity of the OAS Gene Family Is Associated With Increased Severity of Dengue.

Dengue is a mosquito-borne viral disease that afflicts millions of individuals worldwide every year. Infection by any of the 4 dengue virus (DENV) serotypes can result in a spectrum of disease severity. We investigated the impact of variants of interferon-regulated innate immunity genes with a potent antiviral effect on the outcome of DENV infection. We compared the effect of OAS gene family variants on 2 DENV serotypes in cell culture. While both OAS1-p42 and p46 showed antiviral activity against DENV-2, only OAS1-p42 presented anti-DENV-1 activity. Conversely, whereas both OAS3_S381 and R381 variants were able to block DENV-1 infection, the anti-DENV-2 activity observed for OAS3_S381 was largely lost for the R381 variant. By means of an allelic association study of a cohort of 740 patients with dengue, we found a protective effect of OAS3_R381 against shock (odds ratio [OR], 0.37; P < .001). This effect was due to DENV-2 infections (OR, 0.13; P = .007) but was absent for DENV-1, in accordance with the serotype-dependent OAS3 activity found in the functional study. Severe dengue has long been associated with a cytokine storm of unclear origin. This work identifies an early innate immunity process that could lead to the immune overreaction observed in severe dengue and could be triggered by a specific host genotype-pathogen genotype interaction.

A variant in the CD209 promoter is associated with severity of dengue disease.

Dengue fever and dengue hemorrhagic fever are mosquito-borne viral diseases. Dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN1, encoded by CD209), an attachment receptor of dengue virus, is essential for productive infection of dendritic cells. Here, we report strong association between a promoter variant of CD209, DCSIGN1-336, and risk of dengue fever compared with dengue hemorrhagic fever or population controls. The G allele of the variant DCSIGN1-336 was associated with strong protection against dengue fever in three independent cohorts from Thailand, with a carrier frequency of 4.7% in individuals with dengue fever compared with 22.4% in individuals with dengue hemorrhagic fever (odds ratio for risk of dengue hemorrhagic fever versus dengue fever: 5.84, P = 1.4 x 10(-7)) and 19.5% in controls (odds ratio for protection: 4.90, P = 2 x 10(-6)). This variant affects an Sp1-like binding site and transcriptional activity in vitro. These results indicate that CD209 has a crucial role in dengue pathogenesis, which discriminates between severe dengue fever and dengue hemorrhagic fever. This may have consequences for therapeutic and preventive strategies.

Outcomes and predictive factors of pediatric kidney transplants: an analysis of the Thai Transplant Registry.

As universal coverage for pediatric kidney transplantation (KT) was introduced in Thailand in 2008, the number of recipients has been increasing. We evaluated predictive factors for graft failure to understand how to improve clinical outcomes in these children. Using data obtained from the National Transplant registry, we assessed the risk of graft failure using the Kaplan-Meier method and Cox proportional hazards regression. Altogether, 201 recipients aged <21 yr at the time of KT were studied. Living donors (LD) were significantly older than deceased donor (DD). Mean cold ischemia time of DD was 17 h. The mean donor glomerular filtration rate (GFR) was 84.0 mL/min/1.73 m(2) . Induction immunosuppressive therapy was administered more frequently in DD than in LDKT. Delayed graft function (DGF) occurred in 36 transplants. Over 719 person years of follow-up, 42 graft failures occurred. Graft survival at one, three, and five yr post-transplant were 95%, 88% and 76%, respectively. Two factors independently predicted graft failure in multivariate analysis. The hazard ratios for graft failure in patients with DGF and in patients with donor GFR of ≤30 mL/min/1.73 m(2) were 2.5 and 9.7, respectively. Pediatric recipients should receive the first priority for allografts from young DD with a good GFR, and DGF should be meticulously prevented.

Successful continuous venovenous hemofiltration in a neonate with hyperammonemia from ornithine transcabamylase deficiency.

Ornithine transcabamylase (OTC) deficiency is the most common and severe form of abnormal urea synthesis. It can result in hyperammonemia, severe neurologic manifestation, brain edema, and early death. Rapid removal of ammonia by hemodialysis can decrease mortality and morbidity in the patients with severe increase of ammonia levels. However hemodialysis (HD) in infants and young children are technically difficult to perform. Continuous venovenous hemofiltration (CVVH) is increasingly used as an alternative for HD, but performing CVVH in a neonate can be problematic due to small body size and difficult vascular access. The authors reported a successful CVVH using umbilical vein as a vascular access site for ammonia removal in a neonate with OTC deficiency with progressive elevation of plasma ammonia. Technical problems, pitfalls in performing the CVVH, and how the authors overcame the problems are discussed.

Immunogenicity of Hepatitis B Vaccine in Pediatric Systemic Lupus Erythematosus Patients.

BACKGROUND: Pediatric patients with systemic lupus erythematosus (SLE) are at increased infectious risk caused by underlying immunologic dysregulation and immunosuppressive therapy. Hepatitis B virus (HBV) could be reactivated during the immunosuppressive treatment in patients with past HBV infections. Information on immunogenicity after hepatitis B (HB) immunization and reimmunization are still scarce. METHODS: SLE patients 5-18 years of age who had completed a primary HB immunization were enrolled. Anti-HBs levels at enrollment and after each vaccine dose were determined. Patients with anti-HBs levels < 10 mIU/mL were administered 1 booster dose. After 1 booster dose, patients with negative anti-HBs levels were administered 2 more booster doses. RESULTS: Ninety-three SLE patients were enrolled. The prevalence of seroprotection assessed by anti-HBs > 10 mIU/mL after completion of a primary HB immunization was 25.8% (95% CI: 17.2-34.4). Lupus nephritis was associated with unprotective anti-HBs levels [odds ratio (OR): 4.341; 95% CI: 1.044-18.040]. The anti-HBs seroconversion was 72.3% (95% CI: 61.5-83.0) after 1 booster dose and increased up to 93.4% (95% CI: 86.9-98.4) after 3 booster doses. SLE Disease Activity Index-2000 score ≥ 4 (OR: 4.625; 95% CI: 1.45-14.80) was significantly associated with nonseroconversion after the first booster dose. Hypocomplementemia before the first and second booster doses (OR: 27; 95% CI: 1.26-578.35) was significantly associated with nonseroconversion after 3 booster doses. CONCLUSIONS: All pediatric SLE patients should be evaluated for HBV serological status before immunosuppressive treatment. SLE patients with SLE Disease Activity Index-2000 score > 4 should need 3 booster doses if their anti-HBs level was < 10 mIU/mL.

Cytomegalovirus-Specific T Cells in Pediatric Liver Transplant Recipients.

Cytomegalovirus (CMV) infection is a major opportunistic infection after liver transplantation (LT) that necessitates monitoring. Because of the lack of studies in children, we aimed to investigate CMV-specific T cell immune reconstitution among pediatric LT recipients. The recipients were monitored for CMV infection and CMV-specific T cells from the start of immunosuppressive therapy until 48 weeks after LT. Clinically significant CMV viremia (csCMV) requiring preemptive therapy was defined as a CMV load of >2000 IU/mL. Peripheral blood CMV-specific T cells were analyzed by flow cytometry based on IFNγ secretion upon stimulation with CMV antigens including immediate early protein 1 (IE1) Ag, phosphoprotein 65 (pp65) Ag, and whole CMV lysate (wCMV). Of the 41 patients who underwent LT, 20 (48.8%) had csCMV. Most (17/20 patients) were asymptomatic and characterized as experiencing CMV reactivation. The onset of csCMV occurred approximately 7 weeks after LT (interquartile range: 4-12.9); csCMV rarely recurred after preemptive therapy. Lower pp65-specific CD8+ T cell response was associated with the occurrence of csCMV (p = 0.01) and correlated with increased viral load at the time of csCMV diagnosis (ρ = -0.553, p = 0.02). Moreover, those with csCMV had lower percentages of IE1-specific CD4+ and wCMV-reactive CD4+ T cells at 12 weeks after LT (p = 0.03 and p = 0.01, respectively). Despite intense immunosuppressive therapy, CMV-specific T cell immune reconstitution occurred in pediatric patients post-LT, which could confer protection against CMV reactivation.

Depletion of alloreactive T cells for tolerance induction in a recipient of kidney and hematopoietic stem cell transplantations.

The present case report represents a successful attempt to induce transplantation tolerance to organ allograft by combined administration of donor hematopoietic cells and kidney based on in vivo deletion of alloreactive host-vs-graft and graft-vs-host alloreactive T cells following non-myeloablative conditioning. We were able to induce mixed and eventually full donor chimerism and tolerance of kidney allograft in a 15-yr-old male with ESRD after cisplatin treatment and autologous HSCT for mediastinal germ cell tumor. Our approach to induce tolerance was based on preferential depletion of alloreactive T cells induced by exposure to donor's alloantigens and administration of cyclophosphamide at day 2 and day 3 after stem cell infusion. Additional non-specific immunosuppression as part of the conditioning included exposure to two fractions of TLI, treatment with alemtuzumab (monoclonal anti-CD52) and short-term conventional IS treatment to avoid early graft loss, because of request of IRB. Using this approach, with rapid tapering of all conventional IS treatment, the patient maintains good renal functions without evidence of both acute and chronic rejection for 32 months off all medications.

Dengue infection in hematologic-oncologic pediatric patients: aggravation of anemia and bleeding risk.

We studied anemia and bleeding risk among hematologic-oncologic pediatric patients with dengue infection. A total of 907 patients suspected of having dengue infection were included in the study. They were categorized into 2 groups: 1) patients with confirmed dengue infection (n=843) and 2) patients with other febrile illnesses (n = 64). Both groups included patients with underlying hematologic-oncologic diseases (55 vs 14) and without underlying disease (788 vs 50). Patients with underlying diseases were divided into 3 subgroups by risk: Subgroup A, anemia risk, including patients with thalassemia and hemoglobinopathies (n = 39) and G6PD deficiency (n=6); Subgroup B, patients with bleeding risk, including hemophilia (n = 7), von Willebrand disease (n = 1) and thrombocytopenia (n = 4); and Subgroup C, patients with anemia and bleeding risk, including oncologic diseases (n =12). Acute hemolysis in Subgroup A started during the febrile stage and required packed red cell transfusions. Bleeding risk in Subgroup B started during the early febrile stage with vasculopathy and continued to the late febrile stage with thrombocytopenia. These patients required factor concentrate and platelet concentrate transfusions. Anemia and bleeding risk in Subgroup C was greater among patients undergoing chemotherapy than those who had discontinued treatment. The greater the length of time since discontinuation of treatment, the lower risk. The case-fatality rate among dengue infected patients with underlying disease (2/55 = 3.64%) was significantly higher than those without underlying disease 0.63% (5/788).

Clinical outcome of children with Henoch-Schönlein purpura nephritis.

OBJECTIVE: Evaluate the outcomes of pediatric patients with Henoch-Sch6nlein purpura nephritis andfind the parameters correlated with outcomes of treatment. MATERIAL AND METHOD: Review of medical records was performed in twenty patients diagnosed with Henoch-Schinlein purpura nephritis. Demographic data, clinical parameters and records of treatment at diagnosis and the last visit were collected and analyzed. RESULTS: Median age at diagnosis was 8-year-old and median follow-up time was 39 months. All patients had urine protein to creatinine ratio (UPCR) of more than 1.0 g/g while ten patients had hypoalbuminemia. Renal pathology results were class I, II, and III in 2, 14, and 4 patients respectively. Prednisolone was prescribed in all patients and cyclophosphamide was given in 13 patients. All patients had first resolution of proteinuria at median time of six months (range 2-47 months). At the last visit, 13 patients (65%) had remission of proteinuria (remission group), while seven patients (35%) became proteinuric relapse (relapse group) with UPCR > 0.2 g/g. Interestingly, the remission group had median time to first resolution of proteinuria shorter than the relapse group (6 months and 19 months, p < 0.001). Moreover, estimated glomerular filtration rate at diagnosis correlated negatively with UPCR at the last visit (r = -0.773, p = 0.001). CONCLUSION: Pediatric patients with Henoch-Schönlein purpura nephritis who presented with heavy proteinuria had favorable outcome after treatment. The patients who had early resolution ofproteinuria remained in remission more than those who had late resolution.

Clinical Outcomes of Renal Replacement Therapy in Pediatric Acute Kidney Injury: A 10-Year Retrospective Observational Study.

Children with severe acute kidney injury (AKI) have had a high mortality rate despite the use of advanced renal replacement therapy (RRT). This study aims to determine the clinical outcomes and the predictors of survival in pediatric AKI requiring RRT in Thailand. All patients aged 1 month to 18 years with AKI requiring RRT in the Department of Pediatrics, Ramathibodi Hospital from January 1st, 2010 to December 31st, 2019 were enrolled. Clinical and laboratory data were obtained through a medical record review. There were 92 patients with a 45% survival rate. Five factors associated with mortality included multi-organ dysfunction syndrome, presence of sepsis, high pediatric risk of mortality III, use of nephrotoxic drugs, and use of vasopressors. By multivariate analysis, the presence of sepsis and the use of nephrotoxic drugs were independently associated with mortality. Patients with fluid overload ≥10% was associated with poor survival.

Waist-to-height-ratio is associated with sustained hypertension in children and adolescents with high office blood pressure.

Background: Waist-to-height-ratio (WHtR) has been proposed as another indicator for cardiometabolic risk factors including hypertension. Normally, hypertension can be diagnosed in the office setting by detecting high blood pressure for three occasions. However, patients with high office blood pressure may not exhibit high blood pressure outside the office. Ambulatory blood pressure monitoring (ABPM) is a procedure to measure blood pressure over 24-h. Sustained hypertension is characterized as hypertension detected by both office measurement and ABPM. This study aimed to evaluate the performance of WHtR in the diagnosis of sustained hypertension in patients with high office blood pressure. Materials and methods: Demographic data, height, body weight, body mass index (BMI), and waist circumference were retrospectively reviewed in children and adolescents who underwent ABPM due to persistently high office blood pressure. Patients were separated into two groups: a sustained hypertension group and a normal ABPM group. BMI was adjusted to z-score using the WHO Anthroplus software. WHtR was calculated by the formula: waist circumference (cm)/height (m). The performances of different parameters were analyzed using the receiver operating characteristic (ROC) curve and multivariate logistic regression. Results: Sixty patients (63% male) with a mean age of 12.9 ± 3.7 years had persistently high office blood pressure. Twenty-nine (48.3%) had high ambulatory blood pressure parameters so-called "sustained hypertension." The sustained hypertension group had a higher mean BMI z-score (2.32 vs. 1.31, p = 0.01) and a higher mean WHtR (57.7 vs. 49.2 cm/m, p < 0.001) than those of the normal ABPM group. For the diagnosis of sustained hypertension, the ROC analysis revealed that WHtR had a greater area under the ROC curve (AUC) than that of BMI z-score (0.772 vs. 0.723). WHtR remained associated with sustained hypertension (OR 1.2, 95% CI 1.022-1.408, p = 0.026) after adjusting for age, gender, and BMI z-score. Conclusions: Apart from being a more user-friendly metric, WHtR tended to outperform BMI z-score in predicting sustained hypertension in children and adolescents with persistently high office blood pressure.

Associations of lymphocyte subpopulations with clinical phenotypes and long-term outcomes in juvenile-onset systemic lupus erythematosus.

OBJECTIVE: Juvenile-onset systemic lupus erythematosus (JSLE) is a complex and heterogeneous immune-mediated disease. Cellular components have crucial roles in disease phenotypes and outcomes. We aimed to determine the associations of lymphocyte subsets with clinical manifestations and long-term outcomes in JSLE patients. METHODS: A cohort of 60 JSLE patients provided blood samples during active disease, of whom 34 provided further samples during inactive disease. In a longitudinal study, blood samples were obtained from 49 of the JSLE patients at 0, 3, and 6 months. The healthy control (HC) group consisted of 42 age-matched children. Lymphocyte subsets were analyzed by flow cytometry. RESULTS: The percentages of CD4+ T, γδ T, and NK cells were significantly decreased in JSLE patients compared with HC, while the percentages of CD8+ T, NKT, and CD19+ B cells were significantly increased. The percentage of regulatory T cells (Tregs) was significantly lower in JSLE patients with lupus nephritis (LN) than in non-LN JSLE patients and HC. The patients were stratified into high and low groups by the median frequency of each lymphocyte subset. The γδ T cells high group and NK cells high group were significantly related to mucosal ulcer. The CD4+ T cells high group was significantly associated with arthritis, and the NKT cells high group was substantially linked with autoimmune hemolytic anemia. The CD8+ T cells low group was mainly related to vasculitis, and the Tregs low group was significantly associated with LN. The percentage of Tregs was significantly increased at 6 months of follow-up, and the LN JSLE group had a lower Treg percentage than the non-LN JSLE group. Predictors of remission on therapy were high Tregs, high absolute lymphocyte count, direct Coombs test positivity, and LN absence at enrollment. CONCLUSION: JSLE patients exhibited altered lymphocyte subsets, which were strongly associated with clinical phenotypes and long-term outcomes.

Infection-associated hemophagocytic syndrome among patients with dengue shock syndrome and invasive aspergillosis: a case series and review of the literature.

The authors report four autopsy cases of previously healthy children with dengue shock syndrome complicated with infection-associated hemophagocytosis and invasive aspergillosis. Hemophagocytosis is confirmed by histopathology of autopsied reticuloendothelial organs. All four children were identified to have invasive aspergillosis by histopathology and three cases were positive on fungal culture for Aspergillus spp. Regarding the cause of death among the four children without pre-existing underlying disease, three cases were directly ascribable to invasive aspergillosis and the remaining case was ascribed to dengue shock syndrome. The transmigration of preexisting fungi from the respiratory mucosa damaged by the dengue shock process is postulated as the pathogenesis of invasive aspergillosis. The main predisposing factor was found to be prolonged dengue shock syndrome. We reviewed the clinicopathologic features and therapeutic management of infection-associated hemophagocytic syndrome in patients with dengue shock syndrome and invasive aspergillosis.