Raul V. Destura

Details

Sex: Male
Education:

  • Doctor of Medicine, De La Salle University Cavite, 1996

Field of Specialization:

Clostridium Difficile, Tropical Medicine, Antibiotics, Infectious Diseases, Microbiology, Parasitology, HIV

Researches:

Article title: Assessment of the Biosafety and Biosecurity Landscape in the Philippines and the Development of the National Biorisk Management Framework
Authors: Raul Destura, Hilton Y. Lam, Rohani C. Navarro, Jaifred Christian F. Lopez, et al.
Publication title:

Abstract:
Introduction: The emergence of biological threats that can potentially affect millions emphasizes the need to develop a policy framework in the Philippines that can mount an adequate and well-coordinated response. The objective of the study was to assess, strengthen, and harmonize efforts in biorisk management through the development of a National Biorisk Management Framework.

Methods: The development of the National Biorisk Management Framework was carried out in two phases: (1) assessment of the current biosafety and biosecurity landscape and (2) framework development.

Results: This study identified policy gaps in the incorporation of biosafety in course curricula, professional development, and organizational twinning. The desired policy outcomes focus on increasing the capacity and quality of facilities, and the development of the biosafety officer profession. The tabletop exercises revealed weak implementation of existing protocols and unclear coordination mechanisms for emergency response. Based on these, a framework was drafted composed of eight key areas in biosafety and biosecurity, and four key contexts in risk reduction and management.

Discussion and Conclusion: Reforms in biosafety and biosecurity policies are expected to improve coordination, ensure sustainability, capacitate facilities, and professionalize biosafety officers. Because of the complexity of reforms necessary, success will require a consistent and coherent policy framework that (1) provides well-coordinated mechanisms toward harmonized risk reduction and management, (2) establishes and enforces guidelines on biosafety, biosecurity, and biorisk management, (3) regulates facilities essential for occupational safety and public health, and (4) is financed by the General Appropriations Act as part of the national budget.
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Article title: Assessment of a multiplex PCR and Nanopore-based method for dengue virus sequencing in Indonesia
Authors: Samuel C. B. Stubbs, Barbara A. Blacklaws, Benediktus Yohan, Frilasita A. Yudhaputri, et al.
Publication title: Virology Journal 17(1), February 2020

Abstract:
Background: Dengue virus (DENV) infects hundreds of thousands of people annually in Indonesia. However, DENV sequence data from the country are limited, as samples from outbreaks must be shipped across long-distances to suitably equipped laboratories to be sequenced. This approach is time-consuming, expensive, and frequently results in failure due to low viral load or degradation of the RNA genome. Methods: We evaluated a method designed to address this challenge, using the 'Primal Scheme' multiplex PCR tiling approach to rapidly generate short, overlapping amplicons covering the complete DENV coding-region, and sequencing the amplicons on the portable Nanopore MinION device. The resulting sequence data was assessed in terms of genome coverage, consensus sequence accuracy and by phylogenetic analysis. Results: The multiplex approach proved capable of producing near complete coding-region coverage from all samples tested ([Formula: see text] = 99.96%, n = 18), 61% of which could not be fully amplified using the current, long-amplicon PCR, approach. Nanopore-generated consensus sequences were found to be between 99.17-99.92% identical to those produced by high-coverage Illumina sequencing. Consensus accuracy could be improved by masking regions below 20X coverage depth (99.69-99.92%). However, coding-region coverage was reduced at this depth ([Formula: see text] = 93.48%). Nanopore and Illumina consensus sequences generated from the same samples formed monophyletic clades on phylogenetic analysis, and Indonesian consensus sequences accurately clustered by geographical origin. Conclusion: The multiplex, short-amplicon approach proved superior for amplifying DENV genomes from clinical samples, particularly when the virus was present at low concentrations. The accuracy of Nanopore-generated consensus sequences from these amplicons was sufficient for identifying the geographic origin of the samples, demonstrating that the approach can be a useful tool for identifying and monitoring DENV clades circulating in low-resource settings across Indonesia. However, the inaccuracies in Nanopore-generated consensus sequences mean that the approach may not be appropriate for higher resolution transmission studies, particularly when more accurate sequencing technologies are available.
Full text available upon request to the author

Article title: High rates of tenofovir failure in a CRF01_AE-predominant HIV epidemic in the Philippines
Authors: Edsel Maurice T. Salvana, Genesis May J. Samonte, Elizabeth Telan, Katerina Leyritana, et al.
Publication title: International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases (95)

Abstract:
Background: The Philippines has the fastest growing HIV epidemic in the Asia-Pacific. This increase was accompanied by a shift in the predominant HIV subtype from B to CRF01_AE. Increasing evidence points to a difference in treatment responses between subtypes. We examined treatment failure and acquired drug resistance (ADR) in people living with HIV (PLHIVs) after one year on antiretrovirals (ARVs). Methods: PLHIV maintained on ARVs for one year were recruited. Treatment failure was defined as a viral load of ≥1000 copies/mL. Sanger sequencing for genotyping and drug resistance mutation (DRM) detection was performed on patients failing treatment. Results: 513 PLHIV were enrolled. The most common antiretroviral regimens were TDF+3TC+EFV (269) and AZT+3TC+EFV (155). 53 (10.3%) subjects failed treatment. Among these, 48 (90.6%) had DRMs, 84.9% were subtype CRF01_AE. Tenofovir-based regimens performed worse than zidovudine-based regimens (OR 3.28, 95% CI 1.58 to 7.52 p<0.001). Higher rates of NRTI, NNRTI, K65R tenofovir resistance, and multi-class resistance were found compared to those reported in literature. Conclusions: HIV treatment failure at one year of treatment in the Philippines is 10.3%. We found unusually high tenofovir and multiclass resistance, and optimal ARV regimens may need to be reevaluated for CRF01_AE-predominant epidemics.
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Article title: Transmitted and Acquired NNRTI Resistance in the Philippines: Are Newer Generation NNRTIs a Viable Option?
Authors: Nina Theresa Pineda Dungca, Brian Schwem, Geraldine Arevalo, Christian Francisco, et al.
Publication title: Open Forum Infectious Diseases 6(Supplement_2):S870-S870

Abstract:
Background Doravirine, rilpivirine, and etravirine are newer generation non-nucleoside reverse transcriptase inhibitors (NNRTI) that are intended to be more durable alternatives to efavirenz and nevirapine. We examined transmitted drug resistance (TDR) and acquired drug resistance (ADR) to NNRTIs from recent local TDR and ADR data to determine whether these can be useful as first-line or second-line antiretroviral (ARV) agents. Methods We reanalyzed Sanger-Based sequences (SBS) from an ADR surveillance study; and SBS and near-whole-genome next-generation sequences (NGS) from a TDR surveillance study using the Stanford HIV Drug Resistance Database. Results ADR: Out of 513 Filipino PLHIV from an ADR surveillance study on one year of ARV treatment, 53 (10.3%) failed (HIV VL >1,000 copies/mL). Among these, 48 had clinically significant mutations. Table 1 shows NNRTI ADR frequencies. There was no significant ADR difference between first-generation and newer generation NNRTIs. TDR: 298 treatment-naïve Filipino PLHIV underwent baselines sequencing. All 298 had SBS. 266 had successful NGS. Table 1 shows SBS and NGS TDR NNRTI resistance at a 5% minor variant cutoff. There was no significant TDR difference between first-generation and newer generation NNRTIs. Conclusion ADR and TDR rates to the newer NNRTIs are similar to first-generation NNRTIs. High TDR to doravirine on NGS is concerning, but its clinical significance is unclear. Etravirine had the lowest TDR and ADR and may be the most useful new-generation NNRTI. However, integrase strand transfer inhibitor-based regimens will likely be more durable.
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Article title: Prevalence and Molecular Characteristics of MRSA Nasal Carriage Among Hospital Care Workers in a Tertiary Hospital in the Philippines
Authors: Faith Anne Buenaventura-Alcazarena, Angelo dela Tongab, ,Anna Ong-Lima, Raul V. Destura
Publication title: Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi 53(5)

Abstract:
Background Hospital-care workers (HCWs) are at risk for MRSA carriage, subsequent infection and potential transmission of nosocomial infection. Epidemiological typing of MRSA among HCWs would provide data that can be used for control measures. Methods This is a cross sectional study that involved 92 participants from pediatric and surgery department of a tertiary hospital. Nasal swabs were collected and inoculated onto MRSASelect Chromogenic Media. Samples characterized as MRSA underwent SCCmec typing and detection of Panton Valentine leucocidin (PVL) by PCR. Results The overall prevalence of MRSA was 13%. Six were from Pediatrics and another six were from Surgery. Seven out of 12 MRSA isolates carried SCCmec type I gene and five isolates carried SCCmec type IV gene. Six samples were found positive for PVL, four of which PVL-SSCmec IV, while the other two isolates were PVL-SCCmec I. The isolates were grouped into four main sequence types (STs) namely ST 1147, ST30, ST5 and ST97. Two samples from both departments were found to be PVL-positive SCCmec I ST 30; PVL-positive SCCmec IV ST 97 was found in two MRSA samples from Pediatrics and PVL-positive SCCmec IV ST 30 from Surgery. Conclusion Data collected from a non-outbreak setting suggest the presence of different clones of MRSA from nasal swabs of HCWs belonging to the Department of Pediatrics and Surgery. The data collected by this study can be used as reference for other succeeding studies on the surveillance of MRSA among HCWs.
Full text link https://tinyurl.com/ymjwxxpm

Article title: Genotypic persistence of dengue virus in the Philippines
Authors: Ma. Jowina H. Galarion, Brian Schwem, Coleen Pangilinan, Angelo dela Tonga, et al.
Publication title: Infection, Genetics and Evolution: Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases 69

Abstract:
The Philippines is known to have one of the world's highest prevalences of dengue infection. The disease has been endemic in the country since 1956 and the severe form was first reported during an outbreak in Manila in 1954. Among all of the countries in the world, the Philippines had the highest case fatality rate from 2008 to 2012. With the increasing rate of international travel, the country is also considered one of the primary sources of imported dengue cases in non-endemic areas in Asia, Australia, and Europe. Despite this high prevalence, there is a dearth of literature describing the circulating strains in the Philippines at the genotype level. Using data from sequence databases, this study aimed to characterize all available Philippine sequences, at the molecular level. Capsid/pre-membrane (C/prM) junction gene and envelope (E) gene sequences of dengue serotypes 1, 2, 3 and 4 from 1956 to 2016 were used for phylogenetic analysis and genotypic identification. All four serotypes co-circulate in the country over the last 50 years with conspicuous genotypic characteristics. DENV-1 exhibited an apparent persistence of a single genotype since 1974. DENV-2 showed strong evidence of genotypic shift in 1999–2002 accompanied by a genotypic persistence thereafter. DENV-3 and DENV-4 displayed a temporal domination of a single genotype, with evidence of a minor co-circulating genotypic population. The persistence and pre-domination of specific DENV genotypes warrant continuous molecular surveillance for signs of genotypic shifts that can cause local outbreak events or an increased risk for severity.
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Article title: Detection of HIV Transmitted Drug Resistance by Next-Generation Sequencing in a CRF01_AE Predominant Epidemic
Authors: Edsel Maurice Salvana, Nina Theresa Pineda Dungca, Geraldine Arevalo, Katerina Leyritana, et al.
Publication title: Open Forum Infectious Diseases 5(suppl_1):S391-S391

Abstract:
Background The Philippines has the fastest growing HIV epidemic in the Asia-Pacific. Concurrent with this is a subtype shift from B to CRF01_AE. We have previously documented transmitted drug resistance (TDR) locally. However, the lack of drug pressure and the insensitivity of Sanger-based sequencing (SBS) may leave archived drug-resistance mutations (DRMs) undetected. To better detect TDR, we performed next-generation sequencing (NGS) on treatment-naïve patients and compared this with SBS. Methods Following ethics approval, newly-diagnosed adult Filipino HIV patients were recruited from the Philippine General Hospital HIV treatment hub. Demographic data were collected, and blood samples underwent SBS with a WHO-approved protocol. Whole-genome NGS was performed using Illumina HiSeq through a commercial provider (Macrogen, Korea). Genotype and DRMs were analyzed and scored using the Stanford HIV Drug Resistance Database. Results 113 patients were analyzed. Median age was 29 years (range 19–68), mean CD4 count was 147 cells/µL (range 0–556) and median viral load was 2.8 × 106 copies/mL. Genotype distribution was: CRF01_AE (93), B (13), possible CRF01_AE/B recombinants (5), CRF02_AG (1), possible URF (1). TDR prevalence by SBS and NGS at different minority variant cutoffs are shown in Table 1. All DRMs on SBS were found on NGS. Some samples had multiple DRMs. No factors were significantly associated with TDR, genotype, viral load or baseline CD4 count. Conclusion NGS is a more sensitive tool for detecting TDR compared with SBS. Nearly double the DRMs were found at an NGS cutoff of ≥5%, including INSTI DRMs. With increasing HIV drug resistance worldwide, switching to NGS may help decrease rates of initial treatment failure, especially in settings with limited repertoires of ARVs.
Full text link https://tinyurl.com/vh8vnuby

Article title: Emergence of a B/F1 HIV Recombinant in the Philippines: A Potentially New Circulating Recombinant Form
Authors: Brian Schwem, Nina Theresa Pineda Dungca, Geraldine Arevalo, Christian Francisco
Publication title: Open Forum Infectious Diseases 5(suppl_1):S390-S391

Abstract:
Background The Philippines has one of the fastest growing HIV epidemics globally. This was accompanied by a switch from subtype B to CRF01_AE. With a large population of returning overseas workers, new subtypes are being introduced regularly. Because diagnosis of HIV in the Philippines is usually late, superinfections can occur and may give rise to new circulating recombinant forms (CRFs). We propose a new CRF from the Philippines. Methods Following institutional board approval, treatment-naive patients from two HIV treatment hubs (San Lazaro Hospital and the Philippine General Hospital) were recruited. Blood samples underwent Sanger sequencing of the PR and RT regions and next-generation sequencing (NGS) of near-full length genomes. Sequences were analyzed for recombination using the online tool jumping profile Hidden Markov Model (http://jphmm.gobics.de/). Results 247 samples underwent Sanger sequencing of the PR and RT regions of the pol gene. Phylogenetic analysis indicated a clustering of four of the samples. Further analysis showed all four samples had the same breakpoints at nucleotides 2875, 2996, and 3001 (HXB2 numbering). All four patients were male, MSM, with a mean age of 28 years old (24–32), and >10 sexual partners. Mean CD4 count was 464 cells/µL and median viral load was 2.67 × 10⁴ copies/mL. Two patients had sex with foreigners. To get a better overall view of subtype composition, we performed NGS using Illumina HiSeq. NGS showed the majority of the genome to be subtype F1 with segments of subtype B inserted in the pol, vpu, and env genes. A blast analysis of the consensus sequence showed 8,932 out of 8,943 nucleotides (99%) matched a 1999 sample from Argentina. Phylogenetic analysis of these samples show clustering of the four B/F1 recombinants with some South American sequences. No drug resistance mutations were identified. Conclusion Mutation and recombination contribute to the extensive genetic diversity of HIV. Understanding this is important in choosing treatment regimens, developing future vaccines, and pursuing epidemiological investigations. The emergence of a new CRF in the Philippines underlies the importance of conducting routine surveillance for new HIV recombinant forms. Figure 1 View largeDownload slide View largeDownload slide New CRF genome showing subtype components. Figure 1 View largeDownload slide View largeDownload slide New CRF genome showing subtype components. Disclosures All authors: No reported disclosures.
Full text link https://tinyurl.com/25ayfa8e

Article title: Whole genome sequencing and single nucleotide polymorphisms in multi-drug resistant clinical isolates of Mycobacterium tuberculosis from the Philippines
Authors: Marylette Roa, Francis A. Tablizo, El King D Morado, Lovette F Cunanan, et al.
Publication title: Journal of Global Antimicrobial Resistance 15

Abstract:
Thousands of cases of multi-drug resistant Mycobacteria tuberculosis (MTB) have been observed in the Philippines but studies on the genotypes that underlie the observed drug resistance profiles have been lacking. This study aimed to analyse whole genomes of clinical isolates of MTB representing varying resistance profiles to identify single nucleotide polymorphisms (SNPs) in resistance-associated genes. Methods: The genomes of ten MTB isolates cultured from banked sputum sources were sequenced. Bioinformatics analysis consisted of assembly, annotation, and SNPs identification in genes reported to be associated with resistance against isoniazid, rifampicin, ethambutol, streptomycin, pyrazinamide, and fluoroquinolone. Results: The draft assemblies covered an average of 97.08% of the expected genome size. Seven out of ten isolates belonged to the Indo-Oceanic lineage/EA12 Manila clade. Two isolates were classified into Euro-American lineage, while the pre-XDR (pre-extremely drug resistant) isolate was classified under East Asian Beijing clade. The SNPs katG Ser315Thr, rpoB Ser450Leu, and embB Met306Val were found in isoniazid (4/7), rifampicin (3/6), and ethambutol-resistant samples (2/6), respectively, but not in susceptible isolates. Mutations in inhA promoter, pncA, and gyrA known to be involved in resistance against isoniazid, pyrazinamide, and fluoroquinolone respectively, were also identified. Conclusions: This study represents the first effort to investigate whole genomes of Philippine clinical strains of MTB exhibiting various profiles of multi-drug resistance. Whole genome data can provide valuable insights to the mechanistic and epidemiological qualities of tuberculosis in a high burden setting such as the Philippines.
Full text link https://tinyurl.com/43zp28m3

Article title: Effect of maternal supplement beverage with and without probiotics during pregnancy and lactation on maternal and infant health: A randomized controlled trial in the Philippines
Authors: Jacinto Blas V. Mantaring, Raul Destura, Jalil Benyacoub, Sophie Pecquet
Nestlé S.A., et al.
Publication title: BMC Pregnancy and Childbirth 18(1), May 2018

Abstract:
Adequate nutrition is essential during pregnancy and lactation to provide sufficient energy and nutrients to meet the nutritional requirements of the mother, fetus and infant. The primary objective of this study was to assess the effect of a maternal nutritional supplement enriched with probiotics during pregnancy and early lactation on the incidence of infant diarrhea. Methods: Healthy, pregnant (24-28 weeks gestation) women were randomized 1:1:1 to receive either no supplement or two servings per day of an oral supplement (140 kcal/serving) providing 7.9 g protein, multivitamin/minerals, and enriched or not with the probiotics Lactobacillus rhamnosus and Bifidobacterium lactis, from the third trimester of pregnancy until at least 2 months post-delivery. Incidence of infant diarrhea until 12 months post-delivery was analyzed by Poisson regression. The effect on maternal health, fetal growth, and infant growth and morbidity were also evaluated and analyzed by ANOVA. Results: A total of 208 mother/infant pairs were included in the analysis. No significant difference in the incidence of infant diarrhea was observed between the three study groups. The mean maternal weight gains at delivery were similar among groups, despite an increase in caloric intake in the supplemented groups. No statistically significant differences between groups were observed in incidence of pregnancy-related or fetal adverse outcomes. Mean weight-, length-, BMI- and head circumference-for-age z-scores were below the WHO median value for all groups. Post-hoc analysis to compare the effect of the combined supplement groups versus the no supplement group on infant growth parameters showed, at 12 months, that the combined supplemented group had gained statistically significant more weight (8.97 vs. 8.61 kg, p = 0.001) and height (74.2 vs. 73.4 cm, p = 0.031), and had a higher weight-for-age z-score (- 0.62 vs. -0.88, p = 0.045) than the no supplement group. Conclusions: Maternal nutritional supplement with or without probiotics given during late pregnancy and early lactation was well tolerated and safe. Even though no difference in incidence of infant diarrhea was observed between the three groups, the analysis of the combined supplemented groups showed beneficial effects of maternal supplementation on infant weight and length gains at 12 months. Trial registration: ClinicalTrial.gov: NCT01073033 . Registered 17.02.2010.
Full text link https://tinyurl.com/3krds6vz

Article title: Evaluation of fecal and serological tests for the diagnosis of schistosomiasis in selected near-elimination and endemic areas in the philippines
Authors: Raul Destura, Ron Rafael Gabunada, Joy Ann Petronio-Santos, Angelo dela Tonga, et al.
Publication title: The Southeast Asian journal of tropical medicine and public health 49(2), March 2018

Abstract:
Schistosomiasis caused by Schistosoma japonicum is endemic in the Phil-ippines. The Kato-Katz Technique (KKT) is the most commonly used technique for schistosomiasis surveillance, but may have inadequate sensitivity for surveillance. Our study aimed to determine the best schistosomiasis surveillance test(s) for near-elimination and endemic areas in the Philippines. The study population was randomly selected school children aged 9-15 years. The study locations were the provinces of Bohol and Zamboanga del Norte (ZDN) for the near-elimination areas and Agusan del Sur (ADS) for the endemic area. A total of 1,112 study participants were included in the study. Each participant provided a stool and a blood sample to test for schistosomiasis. Each stool sample was examined using the KKT and Formalin Ether Concentration Technique (FECT). Each blood sample was examined using the Circumoval Precipitin Test (COPT), and the Enzyme-Linked Immunosorbent Assay (ELISA) antibody (Ab) and antigen (Ag) tests. We calculated the prevalence of schistosomiasis using each test. We also calculated the sensitivity and specificity of each test in the near-elimination and endemic areas using a combination of the KKT, FECT and ELISA Ag tests as a reference standard. The results showed a zero prevalence in the studied near-elimination areas and a 17.6% prevalence in the studied endemic areas using the KKT; a 0.1% prevalence in the studied near-elimination areas and a 2.5% prevalence in the studied endemic areas using FECT; an 11.0% prevalence in the studied near-elimination areas and a 27.2% prevalence in the endemic areas using the COPT, a 16.8% in the studied near-elimination areas and a 58.5% prevalence in the endemic areas using the ELISA Ab test, and an 8.6% prevalence in the studied near-elimination areas and a 30.5% prevalence in the endemic areas using the ELISA Ag test. The sensitivities were 0.0%, 1.6%, 24.6%, 36.9%, and 98.5% and the specificities were 100.0%, 100.0%, 90.3%, 85.1%, and 100.0% for the KKT, FECT, COPT, ELISA Ab, SoutheaSt aSian J trop Med public health 2
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Article title: HIV Transmitted Drug Resistance in the Philippines: The Case for Baseline Genotyping and Drug Resistance Testing
Authors: Edsel Maurice Salvana, Brian Schwem, Christine Penalosa, Geraldine Arevalo, et al.
Publication title: Open Forum Infectious Diseases 4(suppl_1):S423-S423, October 2017

Abstract:
The Philippines has one of the fastest growing HIV epidemics in the world. Parallel to the increase is a shift in HIV subtype from B to CRF01_AE. No transmitted drug resistance (TDR) surveillance has ever been conducted. With the widespread rollout of antiretrovirals and the limited repertoire of 6 drugs (tenofovir, lamivudine, zidovudine, nevirapine, efavirenz, lopinavir/ritonavir) makes TDR monitoring imperative. In addition, a high rate of hepatitis B (HBV) co-infection (17%) in the general population raises the risk of TDR with prior NRTI monotherapy. Methods Following IRB approval, we performed TDR surveillance at the Philippine General Hospital, one of the largest tertiary referral centers in the country. Treatment-naïve patients had their HIV RT and PR genes sequenced using WHO approved-protocols for HIV genotyping. Generated sequences were analyzed using the Stanford Drug Resistance Database. Pertinent demographic and clinical data were collected. The current results represent year 1 of the study. Results 95 treatment naïve patients were analyzed. Median age was 30 years (range 20–68). There were 88 males and 7 females. Median CD4 count was 90 cells/mL (range 0–936) and median viral load was 1792000 copies/mL. 18 patients were co-infected with HBV, but all denied previous HBV treatment. Conclusion The TDR rate for HIV in the Philippines is 6.3%. This is above the threshold for recommending baseline TDR genotyping for all local HIV patients. All HIV with TDR were subtype CRF01_AE, and this may signal a higher risk of TDR as the epidemic shifts further to a non-B subtype. Disclosures E. M. Salvana, Merck: Scientific Advisor and Speaker’s Bureau, Consulting fee and Speaker honorarium
Full text link https://tinyurl.com/3kcaeyb3

Article title: Predictors of Mortality in Persons Living With HIV in the Philippines: The Impact of Widespread Antiretroviral Therapy and the Case for Early Treatment
Authors: Edsel Maurice Salvana, Katerina Leyritana, Marissa Alejandria, Raul Destura, et al.
Publication title: Open Forum Infectious Diseases 2(Suppl 2):S161

Abstract:

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Article title: Establishment and Comparison of Two Different Diagnostic Platforms for Detection of DENV1 NS1 Protein
Authors: Yin-Liang Tang, Chien-Yu Chiu, Chun-Yu Lin, Chung-Hao Huang, et al.
Publication title: International Journal of Molecular Sciences 16(11):27850-27864, November 2015

Abstract:
Dengue virus (DENV) infection is currently at pandemic levels, with populations in tropical and subtropical regions at greatest risk of infection. Early diagnosis and management remain the cornerstone for good clinical outcomes, thus efficient and accurate diagnostic technology in the early stage of the disease is urgently needed. Serotype-specific monoclonal antibodies (mAbs) against the DENV1 nonstructural protein 1 (NS1), DA12-4, DA13-2, and DA15-3, which were recently generated using the hybridoma technique, are suitable for use in diagnostic platforms. Immunofluorescence assay (IFA), enzyme-linked immunosorbent assay (ELISA) and Western blot analysis further confirmed the serotype specificity of these three monoclonal antibodies. The ELISA-based diagnostic platform was established using the combination of two highly sensitive mAbs (DA15-3 and DB20-6). The same combination was also used for the flow cytometry-based diagnostic platform. We report here the detection limits of flow cytometry-based and ELISA-based diagnostic platforms using these mAbs to be 0.1 and 1 ng/mL, respectively. The collected clinical patient serum samples were also assayed by these two serotyping diagnostic platforms. The sensitivity and specificity for detecting NS1 protein of DENV1 are 90% and 96%, respectively. The accuracy of our platform for testing clinical samples is more advanced than that of the two commercial NS1 diagnostic platforms. In conclusion, our platforms are suitable for the early detection of NS1 protein in DENV1 infected patients.
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Article title: Advancing Cryptosporidium Diagnostics from Bench to Bedside
Authors: Raul V. Destura, Rohani B. Cena, Ma. Jowina H. Galarion, Coleen M. Pangilinan, Geraldine M. Arevalo, et al.
Publication title: Current Tropical Medicine Reports 2(1):150-160, July 2015

Abstract:
Cryptosporidium is increasingly being recognized as an important cause of diarrhea worldwide. Although well known for its impact among HIV positive population, improved diagnostic tests have contributed to its emerging recognition one among the most prevalent causes of early childhood moderate to severe diarrhea, persistent diarrhea, and impaired neurocognitive development. The diagnosis of Crypto-sporidiosis is generally carried out based on availability of skilled microscopist or advanced equipment for molecular-and immunologic-based assays. As an emerging enteric pathogen of medical importance, the need for point-of-care technology is deemed necessary for early identification of the pathogen and application of infection control measures for its potential risk of creating outbreaks. Current point-of-care technologies demonstrate varying sensitivities and specific-ities and may already address the present diagnostic need.
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Article title: Antibiotic management of complicated intra-abdominal infections in adults: The Asian perspective
Authors: Asok Kurup, Kui Hin Liau, Jianan Ren, Min-Chi Lu, et al.
Publication title: Annals of Medicine and Surgery 3(3), September 2014

Abstract:
Regional epidemiological data and resistance profiles are essential for selecting appropriate antibiotic therapy for intra-abdominal infections (IAIs). However, such information may not be readily available in many areas of Asia and current international guidelines on antibiotic therapy for IAIs are for Western countries, with the most recent guidance for the Asian region dating from 2007. Therefore, the Asian Consensus Taskforce on Complicated Intra-Abdominal Infections (ACT-cIAI) was convened to develop updated recommendations for antibiotic management of complicated IAIs (cIAIs) in Asia. This review article is based on a thorough literature review of Asian and international publications related to clinical management, epidemiology, microbiology, and bacterial resistance patterns in cIAIs, combined with the expert consensus of the Taskforce members. The microbiological profiles of IAIs in the Asian region are outlined and compared with Western data, and the latest available data on antimicrobial resistance in key pathogens causing IAIs in Asia is presented. From this information, antimicrobial therapies suitable for treating cIAIs in patients in Asian settings are proposed in the hope that guidance relevant to Asian practices will prove beneficial to local physicians managing IAIs.
Full text link https://tinyurl.com/3zawfujc

Article title: THU0285 Deadly Chik: A Report of Two Atypical and Fatal Cases of Chikungunya Fever Complicated by Severe Vasculitis and Renal Failure
Authors: G. M. Garcia, Nayeli Trinidad, Raul Destura
Publication title: Annals of the Rheumatic Diseases 73(Suppl 2):282-282, June 2014

Abstract:
Background Chikungunya fever (CHIK) is caused by an alphavirus, Chikungunya virus (CHIKV) of the family Togaviridae, is native to tropical Africa and Asia. Symptoms of chikungunya include sudden onset of fever, severe arthralgia, and maculopapular rash. Chikungunya is generally considered self-limiting and has been reported as non-fatal in the past. However, after the March 2005 outbreak in La Réunion Island, there have been several reports of unusually severe complications and deaths. To date, there have been no published reports of severe atypical and fatal cases of Chikungunya fever in the Philippines. We thereby present two cases that initially presented with the usual fever, arthropathy and rash of CHIK, but during the course of their hospital stay, their rash worsened into violaceous, vesiculobullous, and vasculitic lesions over the extremities accompanied by edema and oliguria. Rheumatologic workup and bacterial cultures were negative. Treatment was mainly supportive on admission (NSAIDs, antipyretics). Hydrocortisone was started for arthritis refractory to NSAIDs. Pulse therapy with methylprednisolone was started in the first case once with the appearance of vasculitic lesions, eventually given IVIG infusion as a last resort. They both worsened with the development of acute renal failure and cardiopulmonary collapse necessitating continuous renal replacement therapy, vasopressor and ventilatory support. Despite intensive care, they both succumbed to sudden wide QRS bradyarrhythmias and subsequently died. At post-mortem, RT-PCR was positive for CHIKV Asean genotype 1 for both patients. Conclusions Although it is generally self-limiting, this report illustrates that CHIK can be a rare cause of vasculitis and acute renal failure. Early identification of features of severe disease with timely aggressive therapy may be prudent especially in the elderly population. Mortality with CHIK may be underreported but it should be noted that the risk of complications increases with age. Since there is no specific treatment for CHIK, prevention through vector control and public health education is key.
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Article title: Continued circulation of a single genotype of dengue virus serotype 2 in the Philippines
Authors: Joy Ann G Petronio, Ricky B Vinarao, Kristine Marie G Flores, Raul Destura
Publication title: Asian Pacific Journal of Tropical Medicine 7(1):30-3, January 2014

Abstract:
To obtain descriptive information of behavioral pattern in Chinese school-aged children with cleft lip and palate. A total of 93 cleft lip and palate patients between the age of 6-11 year-old and treated at West China Stomatology Hospital were selected. And another 100 unaffected controls, matched for age and gender, were recruited randomly from a common primary school in Chengdu. Chart review of medical records was used to obtain psychosocial checklists. Scores were compared with published norms and controls to evaluate the risk of problems, separately for three diagnostic groups. The patients group had lower scores of social and academic competencies, especially those with facial deformity or speech problem. No difference was found in the aspect of activity competency. All patients showed elevations in behavior problems. But the type of behavior problems varied in different genders. Chinese school-aged children with cleft lip and palate are at raised risk for social and academic difficulties. Specific pattern of behavior problems displays differently depending on gender of the patient.
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Article title: Clostridium difficile and Entamoeba histolytica infections in patients with colitis in the Philippines
Authors: Cirle Alcantara-Warren, Eternity Labio, Raul Destura, Jesus Emmanuel Allas Dalope Sevilleja, et al.
Publication title: Transactions of the Royal Society of Tropical Medicine and Hygiene 106(7):424-8, May 2012

Abstract:
Amoebiasis is a common cause of non-specific colitis in the Philippines. The prevalence of Clostridium difficile infection with colitis is unknown. Empiric use of metronidazole for colitis treatment is widely practiced. We investigated the association of C. difficile or Entamoeba histolytica infection with endoscopically/histopathologically proven colitis among adults in the Philippines. Two hundred and ten patients undergoing colonoscopy were enrolled. Demographic and clinical data were reviewed. Stool specimens were assayed for C. difficile and E. histolytica by ELISA. Microscopy was performed. The mean age of the patients was 53 y (range: 19–88 y) and 53% were male. Colitis was diagnosed in 39 of 205 patients. Clostridium difficile, E. histolytica and parasites were seen in 17 (43.6%), 10 (25.6%) and 11 (28.2%), respectively, of patients with colitis compared with 36 (21.7%; p = 0.005), 13 (7.8%; p = 0.001) and 56 (33.7%; p = 0.51), respectively, of those without colitis. Diarrhoea and antibiotic intake history were significantly more common among patients with colitis than those without (43.6% and 20.5% vs 18.1% and 5.4%; p = 0.001 and p = 0.006, respectively). The mean duration of diarrhoea was 2.53 d shorter among patients with colitis. The most frequent antibiotics taken were fluoroquinolones and metronidazole (50% and 40% of antibiotic courses, respectively, in patients with colitis). This study suggests that C. difficile infection is common and might be overlooked in settings where amoebiasis and intestinal parasitism are endemic.
Full text available upon request to the author