DENGUE PATIENTS AT PHOTHARAM HOSPITAL: A CLINICAL TRIAL SITE OF DENGUE VACCINE.

Between 2005 and 2013, 1,868 dengue patients, 916 male and 952 female, were admitted to Photharam Hospital, Ratchaburi, Thailand. Among these patients, there were 1,209 with dengue fever (DF), 598 with dengue hemorrhagic fever (DHF), and 61 with dengue shock syndrome (DSS) with 1 death. The disease was seen all year round with a higher incidence in the rainy season. A trend of shift in age group towards older children and adults was seen during the study period. These data show that dengue patient admissions to Photharam Hospital are common, causing a heavy burden on the health system. Only one death was seen during the period of study, indicating that early recognition and effective management of dengue patients occurred. The trend towards higher age in dengue patients during the study period is a problem of concern and needs further clarification.

DENGUE INFECTION IN ELDERLY PATIENTS.

From 2005 to 2013, there were 15 dengue patients aged over 60 years old who were admitted to Photharam Hospital, Ratchaburi, Thailand. Ten were females and five were males. Nine had dengue fever (DF), and 6 had dengue hemorrhagic fever (DHF). A trending shift in age group towards adults has been seen during the past decades. No deaths were seen in these elderly patients with dengue disease, indicating early recognition and effective management of these dengue patients. The trend towards higher age in dengue patients is a problem of concern, which needs further elaboration.

Serum Cortisol as a Biomarker of Severe Dengue.

Dengue infection presents a wide range of clinical symptoms. Serum cortisol is known as a severity predictor of serious infection but is not yet clearly understood in dengue infection. We aimed to investigate the pattern of cortisol response after dengue infection and evaluate the possibility of using serum cortisol as the biomarker to predict the severity of dengue infection. This prospective study was conducted in Thailand during 2018. Serum cortisol and other laboratory tests were collected at four time points: day 1 at hospital admission, day 3, day of defervescence (DFV) (4-7 days post-fever onset), and day of discharge (DC). The study recruited 265 patients (median age (IQR) 17 (13, 27.5)). Approximately 10% presented severe dengue infection. Serum cortisol levels were highest on the day of admission and day 3. The best cut-off value of serum cortisol level for predicting severe dengue was 18.2 mcg/dL with an AUC of 0.62 (95% CI, 0.51, 0.74). The sensitivity, specificity, PPV and NPV were 65.4, 62.3, 16 and 94%, respectively. When we combined serum cortisol with persistent vomiting and day of fever, the AUC increased to 0.76. In summary, serum cortisol at day of admission was likely to be associated with dengue severity. Further studies may focus on the possibility of using serum cortisol as one of the biomarkers for dengue severity.

Discovery and validation of circulating miRNAs for the clinical prognosis of severe dengue.

BACKGROUND: Early prognostic markers of severe dengue may improve case management and reduce dengue-related mortalities. This study aimed to identify circulating microRNAs (miRNAs) as biomarkers for predicting severe dengue. METHODOLOGY: Serum samples from dengue-infected patients were collected on the first day of admission. Patients were followed up for 14 days after admission to determine the final diagnosis. Participants were divided into non-severe and severe dengue, as defined by WHO 2009 criteria. Circulating microtranscriptome analysis was performed using NanoString miRNA Expression Assay. The expression level of candidate miRNAs were then validated by quantitative reverse transcription-PCR method. PRINCIPAL FINDINGS: The discovery cohort (N = 19) lead to the identification of 37 differentially expressed miRNAs between the two groups. Six up-regulated candidate miRNAs were selected and further validated in the larger cohort (N = 135). MiR574-5p and miR1246 displayed the highest diagnostic performance in discriminating between severe from non-severe dengue (ROC-AUC = 0.83). Additionally, miR574-5p and miR1246 had high sensitivity and high negative predictive value for detecting severe dengue. Multivariate analysis suggested that serum miR574-5p was an independent predictor of severe dengue (odds ratio 3.30, 95% CI 1.81-6.04; p<0.001). CONCLUSION: Our study indicated that circulating miRNAs, especially miR-574-5p and miR-1246, might be a promising diagnostic and prognostic biomarker for severe dengue upon hospital admission, especially when using these biomarkers on days 1 to 2 before the onset of severe dengue complications.

Dengue pre-vaccination screening test evaluation for the use of dengue vaccine in an endemic area.

BACKGROUND: The dengue vaccine (Dengvaxia) is only recommended for individuals with prior dengue infection (PDI). This study aimed to perform a serosurvey to inform decision-making for vaccine introduction and identify appropriate target populations. We also evaluated the performance of the serological tests using plaque reduction neutralization test (PRNT) as a reference test in identifying PDI to determine suitability for pre-vaccination screening. METHODS: We enrolled 115 healthy individuals between 10 and 22 years of age living in the Ratchaburi province of Thailand. The serum samples were tested by PRNT to measure the prevalence and concentration of serotype-specific neutralizing antibodies. The performance of the IgG rapid diagnostic test (RDT, SD Bioline, Korea) and IgG enzyme-linked immunosorbent assay (ELISA, EUROIMMUN, Germany) in identifying PDI were evaluated by using PRNT as a reference method. RESULTS: Ninety-four (81.7%) individuals neutralized one or more dengue serotypes at a titer threshold greater than or equal to 10. Multitypic profiles were observed in 70.4% of the samples which increased to 91.9% in subjects aged 19-22. Among monotypic samples, the highest proportion was reactive against DENV-1 followed by DENV-2, DENV-3, and DENV-4. The highest anti-dengue antibody titers were recorded against DENV-1 and increased with age to a geometric mean NT50 titer (GMT) of 188.6 in the 19-22 age group. While both RDT and ELISA exhibited 100% specificity, RDT demonstrated low sensitivity (35%) with ELISA displaying much greater sensitivity (87%). CONCLUSIONS: Almost 80% of adolescents and youth in Ratchaburi province had already been exposed to one or more of the dengue virus serotypes. The dengue IgG RDT displayed low sensitivity and is likely not be suitable for dengue pre-vaccination screening. These results support the use of IgG ELISA test for dengue vaccination in endemic areas.

Fetal poisoning after maternal paraquat ingestion during third trimester of pregnancy: case report and literature review.

INTRODUCTION: Paraquat remains one of the common substances involved in intentional ingestions in Thailand. However, data on outcomes of paraquat ingestion during pregnancy is rarely available and the management is controversial. CASE REPORT: A 17-year-old female in 36 weeks of gestation attempted suicide by ingesting 1/2 a glass of Gramozonetrade mark (paraquat 27.6 % w/v) 5 hours prior to arrival to the hospital. Gastric aspiration and lavage was performed and she was given 50 g of activated charcoal and 150 g of Fuller's Earth suspension. A male infant, weighing 2,390 g with an Apgar score of 71 1010, was delivered via emergency caesarean section 7 hours after ingestion. Due to presence of paraquat in the gastric lavage fluid, the mother was placed on dexamethasone/cyclophosphamide therapy. She developed mild renal insufficiency 63 hours after the ingestion. The infant developed tachypnea immediately after birth that self-resolved. The infant developed tachypnea again on day 6 of life. A chest x-ray revealed right lower lobe infiltration that progressed to diffuse interstitial pattern; subsequent chest x-rays showed evidence of fibrosis. Both mother and infant survived and the infant was discharged and sent home with oxygen 0.5 LPM. Upon follow up at 10 months of age, he still had evidence of chronic lung disease clinically and on chest x-ray. CONCLUSION: Paraquat ingestion during the third trimester of pregnancy usually carries a very poor prognosis. Review of reported literature suggests that this case report represents only the second survival of mother and child.