An Epidemic of Dengue Virus Serotype-4 during the 2015 - 2017: the Emergence of a Novel Genotype IIa of DENV-4 in the Philippines.

Volume 72 no 6, p.413-419, 2019. Page 418, Acknowledgments "We would like to thank all staff and members of the Department of Virology, NEKKEN, Nagasaki University, Japan for providing technical support and advice. Our special thanks to the staff of the Pavilion II and the Central Laboratory of San Lazaro Hospital for their kind assistance during patient recruitment and data collection. We are also very grateful for the support of the Senior Vice President and Head of Research and Biotechnology (R&B) Group of St. Luke's Medical Center, Dr. Isaac David E. Ampil II. Finally, our sincere thanks to the members of R&B's dengue research group for kindly preparing the samples to be transported to NEKKEN." should read "This research was supported by grants from the Japan Agency for Medical Research and Development (AMED) under Grant Number JP18fm0108001, JP19fm0108001 (Japan Initiative for Global Research Network on Infectious Diseases (J-GRID)), AMED Research on Emerging and Re-emerging Infectious Diseases (19fk0108035j0003) and e-ASIA Joint Research Program and; Philippine Council for Health Research and Development (PCHRD) of the Department of Science and Technology (DOST), Philippines, with partial support from the Research and Biotechnology of St. Luke's Medical Center (R&B-SLMC), Philippines (Project No. 07-024). Funders have no role in the study design, data collection, and interpretation, or the decision to submit this work for publication. We would like to thank all staff and members of the Department of Virology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Japan, for providing technical support and advice. Our special thanks to the staff of the Pavilion II and the Central Laboratory of San Lazaro Hospital for their kind assistance during patient recruitment and data collection. We are also very grateful for the support of the Senior Vice President and Head of Research and Biotechnology (R&B) Group of St. Luke's Medical Center, Dr. Isaac David E. Ampil II. Finally, our sincere thanks to the members of R&B's Dengue Research Group for kindly preparing the samples to be transported to NEKKEN."

Autosomal Dominant Frontotemporal Lobar Degeneration in a Filipino Family with Progranulin Mutation.

BACKGROUND: Compared to Western populations, familial frontotemporal lobar degeneration (FTLD) is rare among Asians. Progranulin (GRN) gene mutation, which is a major cause of FTLD, is likewise rare. We present a family with FTLD from the Philippines with an autosomal dominant pattern of inheritance and GRN mutation and briefly review reports of GRN mutations in Asia. CASE PRESENTATION: The proband is 66 years old with progressive nonfluent aphasia (PNFA)-corticobasal syndrome . We assessed 3 generations of her pedigree and found 11 affected relatives with heterogenous phenotypes, usually behavioral variant frontotemporal dementia (FTD) and PNFA. Neuroimaging showed atrophy and hypometabolism consistent with FTD syndromes. White matter hyperintensities were seen in affected members even in the absence of vascular risk factors. A GRN mutation R110X was found in 6 members, 3 with symptoms and 3 were asymptomatic. Plasma GRN was low (<112 ng/mL) in all mutation carriers. No mutations were found in microtubule-associated protein tau, APP, PSEN1, and PSEN2 genes, and all were APOE3. CONCLUSION: This is the first Filipino family with autosomal dominant FTD documented with GRN mutation. Identifying families and cohorts would contribute to therapeutic developments in an area with FTD-GRN.

An Epidemic of Dengue Virus Serotype-4 during the 2015 - 2017: the Emergence of a Novel Genotype IIa of DENV-4 in the Philippines.

Dengue remains a major public health problem in the Philippines. In this study, we determined the circulating dengue serotypes in the Philippines during the 2015-2017 outbreaks using a total of 678 serum samples from 537 individual dengue patients. Following an increase in the number of DENV-4 patients in recent years, we conducted a comprehensive molecular and epidemiology analysis on the DENV-4 strains isolated recently in the Philippines. Two genotypes of DENV-4 have been isolated in the Philippines since 1956: GI and GIIa. The GIIa DENV strains that were isolated in the present study were closely related to a distinct group of GIIa strains that were isolated from the Philippines in 2004. A majority of the isolates of this sub-group have been identified in the Philippines, suggesting that this lineage may have been introduced in the Philippines, and evolved to form the distinct sub-group within GIIa strains. The increase in DENV-4 activity also coincided with the appearance of the GIIa subgroup and the phasing-out of the GI lineage in the Philippines. Overall, our study demonstrates a shift in DENV-4 genotype and epidemic dynamics in a hyperendemic region, suggesting the importance of DENV genetic evolution in establishing and sustaining transmission.

Evaluation of a rapid diagnostic test for detection of dengue infection using a single-tag hybridization chromatographic-printed array strip format.

A dipstick DNA chromatography assay, a single-tag hybridization-printed array strip (STH-PAS), was evaluated for its efficacy to detect dengue virus (DENV). Reverse-transcribed DNA was amplified by PCR, and the amplified DNA was detected using the STH-PAS system. The method was evaluated using stored RNA samples previously identified to carry all 4 serotypes of dengue, chikungunya, and influenza viruses. Clinical performance was also assessed in a prospective study using plasma from 269 febrile cases from the Emergency Department of St. Luke's Medical Center, Quezon City, Philippines, and 30 afebrile normal healthy volunteers. A Taqman real-time PCR (RT-PCR) assay and a rapid Dengue NS1 test, SD Bioline, were used for comparison. The STH-PAS system was more sensitive in detecting dengue infection compared to Taqman RT-PCR. For DENV serotypes 1, 2, and 3, the detection was 1 to 2 dilutions (10-fold) higher, and for DENV serotype 4, the detection was 2-4 dilutions higher. In clinical studies, the STH-PAS system showed 100% sensitivity with 88.9% and 86.6% specificities compared to Taqman RT-PCR and SD Dengue Duo NS1 test, respectively. The STH-PAS system was found to have a superior sensitivity than the Taqman system. Further evaluation of its performance in the field may provide important data to extend its usefulness for surveillance and epidemiological research in outbreak situations.

Draft Whole-Genome Assemblies of Drug-Resistant Clinical Isolates of Klebsiella pneumoniae from the Philippines.

Here, we report the draft assemblies of 11 clinical isolates of Klebsiella pneumoniae that are resistant to cephalosporins, carbapenems, and/or colistin. The assemblies ranged from 5.37 Mbp to 5.70 Mbp in size. Several plasmid sequences were present, and resistance genes spanning multiple classes of antibiotics were predicted.

Emergence of Klebsiella pneumoniae ST273 Carrying blaNDM-7 and ST656 Carrying blaNDM-1 in Manila, Philippines.

We sought to determine the epidemiology of carbapenem-resistant Enterobacteriaceae and to investigate the emergence of carbapenem-resistant Klebsiella pneumoniae in two teaching hospitals in Manila, Philippines. We screened 364 Enterobacteriaceae for carbapenem resistance between 2012 and 2013 and detected four carbapenem-resistant K. pneumoniae isolates from three different patients. We used whole genome sequencing to determine the antibiotic resistance profiles and confirmed the presence of carbapenemase genes by multiplex PCR. We used multilocus sequence typing and PCR-based replicon typing to genetically characterize the carbapenem-resistant isolates. The carbapenemase gene blaNDM was detected in K. pneumoniae isolates from two patients. The first patient had ventilator-associated pneumonia and lumbar shunt infection from K. pneumoniae ST273 carrying blaNDM-7. The second patient had asymptomatic genitourinary colonization with K. pneumoniae ST656 carrying blaNDM-1. The third patient had a gluteal abscess with K. pneumoniae ST1 that did not carry a carbapenemase gene, but did carry blaDHA-1, blaOXA-1, and blaSHV-1. In this study, we report the first cases of blaNDM-carrying pathogens in the Philippines and add to the growing evidence of the worldwide spread of ST273 and NDM-7, a more efficient carbapenem hydrolyzer than NDM-1.

Complete genome sequence of chikungunya virus isolated in the Philippines.

Chikungunya virus is an alphavirus of the Togaviridae family, which causes a febrile illness with arthralgia in humans. We report here on the complete genome sequence of chikungunya virus strain CHIKV-13-112A isolated from a patient in the Philippines who was suspected to have dengue virus. Phylogenetic analysis revealed that the strain is of the Asian genotype.

Allelic and genotype frequencies of catechol-O-methyltransferase (Val158Met) and CYP2D6*10 (Pro34Ser) single nucleotide polymorphisms in the Philippines.

A hospital-based cross-sectional study was conducted to determine the allelic and genotype frequencies in the genes encoding for catechol-O-methyltransferase and CYP2D6*10 among healthy volunteers and patients clinically diagnosed with cancer pain. PCR-RFLP was used to identify COMT and CYP2D6*10 genotypes. Allelic frequencies among healthy volunteer Filipinos were 0.83 and 0.17 for the COMT Val and COMT Met alleles, respectively. Calculated frequencies in Hardy-Weinberg equilibrium (HWE) were 73% for COMT Val/Val, 26% for COMT Val/Met, and 1% for COMT Met/Met genotype. For CYP2D6*10, allelic frequencies in HWE among volunteers were 0.46 for the C allele and 0.54 for the T allele. Twenty percent were identified as homozygous for the wild-type C/C genotype, 56% were identified as heterozygous for the C/T genotype, and 24% were identified as homozygous for the T/T variant genotype. No significant differences in COMT and CYP2D6*10 allele frequencies between cancer patients and healthy volunteers were noted. Our data demonstrated that the allele frequencies of COMT and CYP2D6*10 in the Filipino healthy volunteers were similar with other Asians but markedly different from Caucasian populations.