OBJECTIVE

Dengue remains a critical public health concern in the Philippines. Late consultation and delayed presentation of dengue patients to hospitals constantly challenge doctors. This study aimed to identify factors contributing to late consultation of dengue patients.

This analytic, cross-sectional study examined patient, parental, socioeconomic, cultural, and health system factors influencing delayed consultation among parents of patients 0 – 18 years at Batangas Medical Center and Lipa Medix Medical Center. A total of 668 parents were enrolled. Descriptive statistics and frequency tables summarized the key characteristics. Test of proportions assessed differences between groups. Univariate logistic regression screened possible predictors, followed by multiple logistic regression to identify significant factors.

Univariate analysis identified significant predictors of late consultation, including older patient age(p=0.002), residence >50 km from the hospital (p 50 km from the hospital were 2.7 times more likely to consult late (p=0.01).

Delayed consultation was influenced by the patient age, hospital type, geographic distance from the hospital, maternal marital status, and cultural beliefs in home remedies and faith healing. Strategies to improve early consultation should consider these factors.

OBJECTIVE

To determine whether neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) within the first three days of dengue illness are independent predictors of dengue severity among pediatric patients.

A cross-sectional analytical retrospective study was conducted among pediatric dengue patients admitted to The Medical City, Pasig from September 2021 to August 2024. Data collection was done through electronic chart review. Baseline characteristics were analyzed using the Kruskal-Wallis test, Chi-Square test, and Fisher’s exact test. Receiver Operating Characteristic (ROC) and Area Under the Curve (AUC) analyses, along with diagnostic performance metrics, were used to evaluate daily ratio cut-offs differentiating dengue classifications. Multivariable logistic regression was performed to assess NLR and PLR as independent predictors of warning signs or severe dengue development.

Among the 316 subjects included in the analysis, 40.5% had dengue fever without warning signs, 57.3% had dengue fever with warning signs, and 2.2% had severe dengue. Differentiating patients without warning signs from those with warning signs, the NLR cut-offs were 4.73, 2.07, and 2.5 on days 1-3, respectively, whereas from those with severe dengue, the cut-offs were 1.27, 0.68, and 0.47 on the same days. For this pairwise analysis, PLR cut-offs were 170, 233.92, and 208.79 for the first comparison; and 209.24, 244.12, and 187.5 for the second, respectively. Statistical analysis showed poor discrimination and diagnostic performance for all cut-offs. Likewise, multivariable linear regression revealed no significant correlation between either ratio and dengue severity.

NLR and PLR within the first three days of dengue illness revealed poor performance in predicting the development of warning signs or progression to severe dengue among pediatric patients.

Dengue hemorrhagic fever is a severe form of dengue presenting commonly with bleeding diathesis, but rarely with peripheral nervous system manifestations. Proximal median neuropathy comprises 1% of upper limb compression syndromes, and this case is the first to report injury to the proximal median nerve due to compression from hematoma formation. This case report presents the rehabilitation process of a 25-year-old Filipino female median nerve entrapment from venipuncture-associated hematoma presenting as burning sensation on the medial elbow, forearm and hand, weak flexion movement of her left thumb, index, and middle fingers. The patient was managed conservatively with pain medications, range of motion, gross and fine motor, and sensory re-education exercises. At 12 months, there was partial but functional recovery of median motor distribution and full recovery of median sensory distribution, as evidenced by improved sensory nerve action potential conduction velocity and amplitude, and compound motor action potential conduction velocity, with persistent decreased amplitude at 50%, and decrease in cross-sectional area of the left median nerve.

This paper highlights the functional outcomes of a conservatively managed median nerve entrapment from venipuncture hematoma from dengue hemorrhagic fever. This case report also emphasizes that in the presence of severe bleeding risk of surgery in the background of severe thrombocytopenia, timely rehabilitation medicine referral with monitoring through clinical evaluation, musculoskeletal ultrasound, and electrodiagnostic study presents a viable alternative in the management of compression neuropathy.

BACKGROUND

Dengue is a global health concern, particularly in tropical regions such as the Philippines. In 2019,Cebu City reported the highest number of dengue cases in Central Visayas with 3,290 cases and 20 deaths, an 11.8% increase compared to 20181 . To help predict disease outcomes and provide timely management, a scoring system, the Daily Dengue Severity Score (DDSS)² was utilized.

To determine the clinicodemographic profile of dengue patients, determine the accuracy of the DDSS in assessing disease severity, and determine a cut off score that suggests severe dengue.

Patients 1 month to 18 years admitted for dengue at Perpetual Succour Hospital from January 2018 to December 2020 were included. Cases were classified as Dengue without Warning Signs, Dengue with Warning Signs, and Severe Dengue, and scored using the DDSS. Statistical analysis used were Geometric mean and Area Under the Receiver Operating Characteristic (AUROC) curves to analyze the discriminative performance of the DDSS among the different disease severity states.

Out of 327 cases, 34 were classified as Dengue without Warning Signs, 271 Dengue with Warning Signs, and 22 Severe Dengue. The highest mean DDSS was 17.7 ±14.0 at Day -4 among those with Severe Dengue, and the lowest mean DDSS was 1.1 ± 2.0 at Day +3 among those with Dengue without Warning Signs. A cut off point of 10 on Day -1 predicted subsequent Severe Dengue among patients with Dengue with Warning Signs. In 91.39% of cases, there was a significant relationship between the DDSS and dengue classification, and the higher the DDSS, the more severe the disease.

Majority of dengue patients were males, aged 8.1 to 9.2 years. DDSS showed 66.67% sensitivity, 92.86% specificity, a positive likelihood ratio of 9.3, and a cutoff of 10 is predictive of severe dengue among patients with dengue with warning signs.

OBJECTIVE: This paper aimed to describe the clinical profile and short-term clinical outcomes of children with Acute Kidney Injury (AKI) requiring hemodialysis in a tertiary pediatric hospital. MATERIALS AND METHODS: A retrospective cohort on in-patients who received hemodialysis treatments at our institution was performed. Medical charts of patients admitted between July 2018 and July 2023 were retrieved. Demographic data, clinical profiles and subsequent outcomes in terms of mortality and recovery or non-recovery from AKI were recorded. RESULTS: After meeting the inclusion and exclusion criteria, 129 patients were included in the study‘s statistical analysis. There was an even distribution between males and females. The average age of treated patients was 10 years old (SD ± 4.3). The average weight of patients was 35kg (SD ± 16.9). The most common diagnosis of patients was severe dengue (21.7%), followed by severe sepsis (14.7%). More than half of patients (51.9%) had an existing co-morbidity, of which Systemic Lupus Erythematosus (22.4%) and solid tumors (22.4%) were most common. The most common indication for hemodialysis was uremia (52.7%). In terms of short-term outcome, majority of patients died during the same admission (56.5%), while 31 patients (24.0%) recovered. CONCLUSION The clinical profile of patients who underwent hemodialysis treatments for AKI were comparable to international data. The study did not differentiate deaths from AKI or underlying illness, but demonstrated a higher mortality rate compared to other existing studies. This study is the first known local paper to describe the profile and outcomes of children who received hemodialysis for AKI.
Hemodialysis ; Renal Dialysis ; Severe Sepsis ; Sepsis ; Severe Dengue

Objective To investigate the relationship between disease courses and severity and monocyte subsets distribution and surface CD31 intensity in patients of hemorrhagic fever with renal syndrome (HFRS). Methods Peripheral blood samples from 29 HFRS patients and 13 normal controls were collected. The dynamic changes of classical monocyte subsets (CD14⁺⁺CD16^-), intermediated monocyte subsets (CD14⁺⁺CD16⁺) and non-classical monocyte subsets (CD14⁺CD16⁺⁺) and the mean fluorescent intensity (MFI) of CD31 on monocyte subsets were detected by multiple-immunofluorescent staining and flow cytometry. Results In acute phase of HFRS, the ratio of classical monocyte subsets to total monocytes was dramatically decreased compared to convalescent phase and normal control. It was still much lower in convalescent phase compared to normal controls. The ratio of classical monocyte subsets to total monocytes were decreased in HFRS patients compared to that in normal control, whereas there was no difference between severe/critical groups and mild/moderate groups. On the contrary, the ratio of intermediate monocyte subsets to total monocytes in acute phase of HFRS was significantly increased compared to convalescent phase and normal control. The ratio of intermediate monocyte subsets to total monocytes were increased in HFRS patients compared to that in normal control, whereas no difference was found between severe/critical groups and mild/moderate groups. Phases or severity groups had no difference in ratio of non-classical monocyte subsets to total monocytes. Additionally, the ratio of classical monocyte subsets had a tendency to decline and that of intermediate monocyte subsets showed an increase both to total monocytes between the acute and convalescent phases in 11 HFRS patients with paired-samples. Moreover, in acute phase of HFRS, the mean fluorescent intensity (MFI) of CD31 on three monocyte subsets all decreased, specifically classical monocyte subsets showed the highest MFI of CD31 while the normal control reported the highest MFI of CD31 in non-classical monocyte subsets. In convalescent phase, the MFI of CD31 on classical and intermediated monocyte subsets were both lower than that of normal control, while MFI of CD31 was still significantly lower than normal control on non-classical monocyte subsets. Finally, MFI of CD31 on classical and intermediated monocyte subsets in severe/critical group were both lower than those in mild/moderate group, showing no statistical difference in MFI of CD31 on non-classical monocyte subset across groups of different disease severity. Conclusion The ratio of classical and intermediated monocyte subsets to total monocytes are correlated with the course of HFRS, and so are the surface intensity of CD31 on these monocyte subsets with the disease course and severity. The surface intensity of CD31 on non-classical monocyte subsets, however, is correlated only with the course of the disease. Together, the underlying mechanisms for the observed changes in monocyte subsets in HFRS patients should be further investigated.
Humans ; Monocytes ; Lipopolysaccharide Receptors ; Hemorrhagic Fever with Renal Syndrome ; Receptors, IgG ; Disease Progression

The prevalence of dengue infection poses a great public health concern among people living in tropical and subtropical countries like the Philippines. Just recently in 2019, the Philippines had a dengue virus (DENV) outbreak where nearly half of the mortalities were children between 5 and 9 years of age, and around 73% of confirmed DENV cases were under the age of 19. Children are disproportionately affected and are considered to be highly vulnerable to severe dengue infection compared to adults due to several factors. These include: immunological differences--poorly developed immune systems, making them more susceptible to the virus; smaller body sizes and weight means that they are more likely to experience severe symptoms; and their tendency to play outdoors, make them more exposed to mosquito bites. Hence, this article provides an overview of the current understanding for the vulnerability of children to severe dengue infection compared to adults
dengue virus ; dengue shock syndrome

Objective: To explore the impact of health management measures for entry personnel (entry management measures) against COVID-19 on the epidemiological characteristics of imported Dengue fever in Guangdong Province from 2020 to 2022. Methods: Data of imported Dengue fever from January 1, 2016 to August 31, 2022, mosquito density surveillance from 2016 to 2021, and international airline passengers and Dengue fever annual reported cases from 2011 to 2021 in Guangdong were collected. Comparative analysis was conducted to explore changes in the epidemic characteristics of imported Dengue fever before the implementation of entry management measures (from January 1, 2016 to March 20, 2020) and after the implementation (from March 21, 2020 to August 31, 2022). Results: From March 21, 2020, to August 31, 2022, a total of 52 cases of imported Dengue fever cases were reported, with an imported risk intensity of 0.12, which were lower than those before implementation of entry management measures (1 828, 5.29). No significant differences were found in the characteristics of imported cases before and after implementation of entry management measures, including seasonality, sex, age, career, and imported countries (all P>0.05). 59.62% (31/52) of cases were found at the centralized isolation sites and 38.46% (20/52) at the entry ports. However, before implementation of entry management measures, 95.08% (1 738/1 828) of cases were found in hospitals. Among 51 cases who had provided entry dates, 82.35% (42/51) and 98.04% (50/51) of cases were found within seven days and fourteen days after entry, slightly higher than before implementation [(72.69%(362/498) and 97.59% (486/498)]. There was significant difference between the monthly mean values of Aedes mosquito larval density (Bretto index) from 2020 to 2021 and those from 2016 to 2019 (Z=2.83, P=0.005). There is a strong positive correlation between the annual international airline passengers volume in Guangdong from 2011 to 2021 and the annual imported Dengue fever cases (r=0.94, P<0.001), and a positive correlation also existed between the international passenger volume and the annual indigenous Dengue fever cases (r=0.72, P=0.013). Conclusions: In Guangdong, the entry management measures of centralized isolation for fourteen days after entry from abroad had been implemented, and most imported Dengue fever cases were found within fourteen days after entry. The risk of local transmission caused by imported cases has reduced significantly.
Animals ; Humans ; COVID-19 ; Aedes ; Epidemics ; China/epidemiology* ; Dengue/epidemiology*

Objective To perform quality control in live attenuated yellow fever vaccine(chicken embryo cell)virus seed bank at the genomic level using the new generation Illumina/Solexa sequencing platform.Methods The live attenuated yellow fever vaccine strain YF17D-204 was inoculated into primary chicken embryo cells,and the chicken embryo cell adapted strains of live attenuated yellow fever vaccine were screened to establish YFV17D-CEC tertiary virus seed bank. The genome RNA of virus seeds was extracted,and the RNA library was prepared. The new generation Illumina/Solexa sequencing platform was used for high-throughput RNA sequencing. The whole genome nucleic acid sequence of yellow fever virus was systematically analyzed by using biological softwares such as FastQC,Trimmomatic,SPAdes,GapFiller,PrInSeS-G,Prokka,RepeatMasker,CRT,NCBI Blast~+,KAAS,HMMER3,TMHMM,SignalP,LipoP,ProtCamp and MegAlign.Results The whole genome of YFV17D-CEC tertiary virus seed bank contained 10 862 nucleotides,including an open reading frame(ORF)from 119 to 10 354(10 236 bp),encoding 3 412 amino acids. Sequence alignment analysis showed that the sequence of YF17D-CEC tertiary virus seed bank was 100% identical with YFV17D RKI(JN628279.1),YF/Vaccine/USA/Sanofi-Pasteur-17D-204/UF795AA/YFVax(JX503529.1)and YFV17D-204(KF769015.1),and no mutation occurred in the whole genome of the tertiary virus seed bank. Comparison of the sequences of different live attenuated yellow fever vaccine strains showed that yellow fever virus had multiple polymorphic sites.Conclusion YFV17DCEC has good genetic stability in primary chicken embryo cells. High-throughput RNA sequencing technology can quickly detect the whole genome information of YF17D-CEC virus seed bank,and the sequence analysis data can be used in the gene level quality control of yellow fever vaccine virus seed banks.
High-throughput RNA sequencing ; Live attenuated yellow fever vaccine ; Gene expression ; Virus seed bank ; Quality control

OBJECTIVE: To analyze the differentially phosphorylated proteins in DENV-2-infected human umbilical venous endothelial cells (HUVECs) and explore the possible pathogenic mechanism of DENV-2 infection. METHODS: The total proteins were extracted from DENV-2-infected HUVECs and blank control HUVEC using SDT lysis method. The phosphorylated proteins were qualitatively and quantitatively analyzed using tandem mass spectrometry (TMT). The identified differentially phosphorylated proteins were analyzed by bioinformatics analyses such as subcellular localization analysis, GO enrichment analysis, KEGG pathway analysis and protein-protein interaction (PPI) analysis. Western blotting was used to detect the expressions of phosphorylated Jun, map2k2 and AKT1 proteins in DENV-2-infected HUVECs. RESULTS: A total of 2918 modified peptides on 1385 different proteins were detected, and among them 1346 were significantly upregulated (FC > 1.2, P < 0.05) and 1572 were significantly downregulated (FC < 0.83, P < 0.05). A total of 49 phosphorylated conserved motifs were obtained by amino acid conservative motif analysis. The most abundant differentially phosphorylated peptides in protein domain analysis included RNA recognition motif, protein kinase domain and PH domain. Subcellular localization analysis showed that the differentially modified peptides were mainly localized in the nucleus and cytoplasm. GO enrichment and KEGG pathway analysis showed that the differential peptides were mainly enriched in the regulation of stimulation response, biosynthesis of small molecules containing nuclear bases, and migration of phagosomes and leukocytes across the endothelium. PPI and KEGG joint analysis showed that the up-regulated and down-regulated differentially phosphorylated proteins were enriched in 15 pathways. In DENV-2-infected HUVECs, Western blotting detected differential expressions of phosphorylated proteins related with the autophagy pathway, namely JUN, MAP2K2 and AKT1, and among them p-JUN was significantly down-regulated and p-AKT1 and p-MAP2K2 were significantly upregulated (P < 0.01). CONCLUSION DENV-2 infected HUVECs show numerous differentially expressed proteins. The downregulation of p-JUN and upregulation of p-MAP2K2 and p-AKT1 suggest their potential roles in regulating autophagy, which is probably involved in the mechanism of DENV-2 infection.
Humans ; Autophagy ; Cell Death ; Cell Nucleus ; Human Umbilical Vein Endothelial Cells/virology* ; Dengue ; Proteome