Predominance of DS-1-like G8P[8] rotavirus reassortant strains in children hospitalized with acute gastroenteritis in Thailand, 2018-2020.

Rotavirus A (RVA) is an important cause of acute gastroenteritis (AGE) in children. This study aims to investigate the molecular epidemiology of RVA in children hospitalized with AGE in Chiang Rai, Thailand in 2018-2020 by reverse transcription polymerase chain reaction. Of 302 samples, RVA was detected in 11.6% (35 samples): 11.3% (19/168) in 2018-2019 and 11.9% (16/134) in 2019-2020. G8P[8] was the predominant genotype at 68.4% in 2018-2019 and 81.2% in 2019-2020. G1P[8] (15.8%), G2P[4] (5.3%), G3P[8] (10.5%) in 2018-2019, and G9P[8] (18.8%) in 2019-2020 were also detected. Whole-genome analysis of G8P[8] revealed a DS-1-like genetic backbone: G8-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2. Phylogenetically, the VP7 genes of G8P[8] clustered in a major lineage with previously published 51 DS-1-like G8P[8] reference strains, closely related to 13 G8P[8] strains from Thailand and China. These G8P[8] strains contained two unique amino acid substitutions (A125S and N147D) in the VP7 antigenic epitopes. In addition, the VP1 and NSP2 genes of G8P[8] clustered in lineages separated from the DS-1-like G8P[8] reference strains with a high genetic divergence but were closely related to G1P[8], G2P[4], G3P[8], or G9P[8]. Several amino acid differences were observed in the VP7 and VP8* antigenic epitopes of G8P[8] compared with RVA vaccine strains. Homology modeling confirmed that these different amino acid residues were located on the surface-exposed area of the structure. Taken together, the genetic analysis clearly defines the Chiang Rai DS-1-like G8P[8] strains as a novel reassortant strain that might have evolved genetically through reassortment events and consequently received their VP1 and NSP2 genes from locally cocirculating-RVA genotypes.

Clinical Characteristics and Outcome of Children Hospitalized With Scrub Typhus in an Area of Endemicity.

BACKGROUND: Scrub typhus, caused by Orientia tsutsugamushi, is a major cause of acute febrile illness in children in the rural tropics. METHODS: We recruited 60 febrile pediatric patients with a positive scrub typhus rapid diagnostic test result and 40 healthy controls from Chiang Rai Province in northern Thailand. Diagnosis was confirmed by the detection of (1) O. tsutsugamushi-specific DNA in blood or eschar samples with a polymerase chain reaction assay, (2) a fourfold rise in immunoglobulin M (IgM) titer to ≥1:3200 in paired plasma samples with an indirect immunofluorescence assay (IFA), or (3) a single IgM titer of ≥1:3200 in an acute plasma sample with an IFA. Demographic, clinical, and laboratory data were collected, and patients were followed up for 1 year. RESULTS: Diagnosis was confirmed in 35 (58%) of 60 patients, and all controls tested negative for scrub typhus. Patients with confirmed scrub typhus had clinical symptoms, including fever (35 of 35 [100%]), eschar (21 of 35 [60%]), cough (21 of 35 [60%]), tachypnea (16 of 35 [46%]), lymphadenopathy (15 of 35 [43%]), and headache (14 of 35 [40%]). Only 4 (11%) of 35 patients received appropriate antibiotic treatment for scrub typhus before admission. The median fever-clearance time was 36 hours (interquartile range, 24-53 hours). Complications observed include hepatitis (9 of 35 [26%]), severe thrombocytopenia (7 of 35 [20%]), pneumonitis (5 of 35 [14%]), circulatory shock (4 of 35 [11%]), and acute respiratory distress syndrome (3 of 35 [9%]). Treatment failure, defined by failure to defervesce within 72 hours of antibiotic treatment initiation, was noted in 8 (23%) of 35 patients, and 1 (3%) of the 35 patients died. No evidence of relapse or reinfection was found. CONCLUSION: Pediatric scrub typhus in northern Thailand is often severe and potentially fatal with delays in treatment a likely contributing factor. Additional studies to investigate the bacterial, pharmacologic, and immunologic factors related to treatment outcome along with measures to improve public awareness should be prioritized.

Emergence of G9P[8] rotaviruses in children with acute gastroenteritis in Thailand, 2015-2016.

Human group A rotavirus is a major contagious virus causing gastroenteritis in children. Molecular epidemiological study of group A rotavirus infections in hospitalized children was performed by multiplex RT-PCR during 2015-2016 in Chiang Rai, Thailand. G- and P-genotypes of positive rotavirus samples were further analyzed by one-step and two-step multiplex RT-PCR methods. Among 270 fecal specimens tested, rotavirus was the most prevalent (33.7%), followed by norovirus GII (4.1%), adenovirus (3%), and astrovirus (1.5%). Infection was common in patients aged 12-23 months (45.1%) and occurred mostly in children under 3 years of age (85.7%). The highest peak was in a hot month, March (64.8%). G9P[8] emerged as the most predominant (79.1%), followed by G3P[8] (13.2%), G1P[8] (3.3%), and mixed G-types (4.4%). Interestingly, Chiang Rai G9 strains were clustered within a distinct lineage VII including G9 recently reported since 2010-2015. G9-VII also contained four to five unique amino acid substitutions in the VP7 proteins compared with those of the G9 candidate vaccine strain RVA/Human-tc/IND/116E/1985/G9P[11] and the prototype RVA/Human-wt/USA/WI61/1983/G9P[8], defining the G9-VII as a novel variant. G3 strains were closely related to the "new G3P[8] reassortant variant" with an equine-like VP7 gene that emerged in several countries. This study contributes to the understanding of the genetic diversity, providing scientific support for future vaccine strategies to reduce the morbidity and mortality.

Randomized Controlled Trial of Azithromycin versus Doxycycline or Chloramphenicol for Treatment of Uncomplicated Pediatric Scrub Typhus.

OBJECTIVE: To evaluate the efficacy and safety of azithromycinfor treatment of uncomplicated pediatric scrub typhus. MATERIAL AND METHOD: A randomized controlled trial was performed. We compared azithromycin with doxycycline or chloramphenicol in uncomplicated pediatric scrub typhus from inpatient pediatric department of Chiangrai Prachanukroh Hospital. The primary outcome was cure rate at day 3. The secondary outcomes were timing to defervescence within 72 hours, side effects, and relapsed rate. We compared data between both groups with Fisher's exact test or Mann-Whitney U test, and failure rate was demonstrated by Kaplan-Meier survival curve and Log-rank test. RESULTS: We included 57 patients, ofwhom, 28 were assigned to doxycycline or chloramphenicol (control group) and 29 to azithromycin (study group). The baseline characteristics of both groups were similar The cure rate was 85.7% in the doxycycline or chloramphenicol group, as compared to 79.3% in the azithromycin group (p = 0.73), and a median time to defervescence was 30 hours (IQR 21, 48) vs. 36 hours (IQR 20, 68) respectively (p = 0.166). There was a little minor side effect in azithromycin group. No relapsed was found in either groups. CONCLUSION: Azithromycin was as effective as doxycycline or chloramphenicol in treatment of uncomplicated pediatric scrub typhus.

Efavirenz Concentrations and Probability of HIV Replication in Children.

In 188 HIV-infected children receiving efavirenz, a lower mid-dose (C12) was associated with a higher risk of HIV-1 viral load >400 copies/mL (P = 0.03). Simulations for a normalized population receiving US Food and Drug Administration weight-band dosing predicted that 15% of children would have a C12 below target threshold (<1.0 mg/L) with a 23% risk of viral replication.

Bacterial etiology of empyema thoracis and parapneumonic pleural effusion in Thai children aged less than 16 years.

This study aimed to identify the bacterial etiology of empyema thoracis or parapneumonic pleural effusions in Thai children, with a focus on pneumococcus. This hospital-based, descriptive study included children aged < or = 16 years, diagnosed with empyema thoracis or parapneumonic pleural effusion, from whom a pleural fluid (PF) sample was taken between January 2008 and November 2009. PF and blood samples were cultured and PF samples were also tested by polymerase chain reaction (PCR) to assess whether evidence of an infection might be identified among culture-negative samples. Serotyping of Streptococcus pneumoniae-positive samples was performed by molecular techniques and Quellung reaction. In this study, 29 children with empyema thoracis and 42 children with parapneumonic pleural effusion were enrolled. Potentially pathogenic bacteria were cultured in 13/71 samples at local or central laboratories; the most common bacteria were Staphylococcus aureus (8 children) and S. pneumoniae (2 children). Molecular techniques detected one or more targeted respiratory pathogens in 18/71 PF samples. S. pneumoniae and Haemophilus influenzae were identified by PCR in 13 and 6 children, respectively; PCR for S. aureus was not performed. The pneumococcal serotypes identified were 1, 3, 5, 6A/B, 9A/V, 14, 15A, 19F and 23A. This study shows that among Thai children with empyema thoracis and parapneumonic pleural effusions, S. aureus and S. pneumoniae were the most common pathogens identified by culture and PCR, respectively. These findings confirmed that molecular techniques are more sensitive for identification of S. pneumoniae and H. influenzae and enhance detection of important bacterial causes of empyema.

Hepatic dysfunction in pediatric scrub typhus: role of liver function test in diagnosis and marker of disease severity.

OBJECTIVE: Determine the frequency of abnormalities of liver function test in children with scrub typhus and its relation with severity of disease. MATERIAL AND METHOD: Fifty-four children diagnosed with scrub typhus at Chiang Rai Regional Hospitalfrom January 2004 to December 2005 were studied. The diagnosis of scrub typhus in the present study was based on a single indirect immunofluorescent antibody (IFA) titer against O tsutsugamushi of > or = 1:400 or a four fold or greater rise in IFA titer to at least 1:200. Liver function tests (LFT) were done on the first few days of admission in all patients. Abnormalities of LFT were focused on serum AST, ALT albumin and total bilirubin level. All of the patients were divided into two groups based on the presence or absence of complications. RESULTS: Fifty-two patients (96.3%) had abnormal LFT. Evaluation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were detected in 52 (96.3%) and 36 (66.7%) cases, respectively. Hypoalbuminemia and hyperbilirubinemia were detected in 23 (42.6%) and 4 (7.4%) cases, respectively. The higher level of AST, ALT and lower level ofserum albumin correlated significantly with the severity of scrub typhus in children. CONCLUSION: Hepatic dysfunction is common in children with scrub typhus. Elevation of AST level may be used as a screening test for diagnosis of scrub typhus in areas where rapid diagnostic test is not commercially available. Increased AST, ALT and hypoalbuminemia related with severity of disease.

Clinical study of 20 children with scrub typhus at Chiang Rai Regional Hospital.

20 children, diagnosed with scrub typhus who attended Chiang Rai Regional Hospital during a period of 6 months from June 2003 to December 2003, were studied prospectively. All cases were serologically proved to be scrub typhus by using Dipstick or indirect immunofluorescent antibody (IFA) technique. The most common clinical feature was eschar (75%). Others included hepatomegaly (65%), cough (60%), lymphadenopathy (40%), tachypnea (35%), constipation (25%), abdominal pain (20%), edema (20%), splenomegaly (15%), vomiting (15%), rash (15%) and petichia (5%) respectively. Chest radiography showed abnormalities in 85% with mostly bilateral interstitial infiltrations. Elevated of SGOT: SGPT were detected in 18 (90%) and 15 (75%) cases. Hypoalbuminemia was detected in 12 (60%) cases. Complete blood count showed PMN leukocytosis (> 60%) in 12 (60%) cases, lymphocytosis (> 40%) and atypical lymphocytosis (> 5%) in 1 (5%) case each and thrombocytopenia in 16 (80%) cases. The Weil-Felix test was positive in 1 (5%) case. Complications were pneumonia with or without pulmonary edema, meningitis and shock. Chloramphenicol and doxycycline were successfully treated and roxithromycin was not effective.

Congenital tuberculosis presenting as sepsis syndrome.

A 20 day old male infant presented with fever, respiratory distress and poor feeding for 7 days. He was referred from a community hospital and diagnosed as sepsis. Physical examination revealed hepatosplenomegaly. A chest radiograph showed miliary infiltration of both lungs. Smear of gastric washing for AFB was positive. Congenital tuberculosis was diagnosed, the infant was successfully treated with antituberculous drugs and followed up monthly for 1 year. He had good health and normal development after the illness.