Whole genome sequencing analysis of Mycobacterium tuberculosis reveals circulating strain types and drug-resistance mutations in the Philippines.

The Philippines is a high-incidence country for tuberculosis, with the increasing prevalence of multi- (MDR-TB) and extensively-drug (XDR-TB) resistant Mycobacterium tuberculosis strains posing difficulties to disease control. Understanding the genetic diversity of circulating strains can provide insights into underlying drug resistance mutations and transmission dynamics, thereby assisting the design of diagnostic tools, including those using next generation sequencing (NGS) platforms. By analysing genome sequencing data of 732 isolates from Philippines drug-resistance survey collections spanning from 2011 to 2019, we found that the majority belonged to lineages L1 (531/732; 72.5%) and L4 (European-American; n = 174; 23.8%), with the Manila strain (L1.2.1.2.1) being the most prominent (475/531). Approximately two-thirds of isolates were found to be at least MDR-TB (483/732; 66.0%), and potential XDR-TB genotypic resistance was observed (3/732; 0.4%), highlighting an emerging problem in the country. Genotypic resistance was highly concordant with laboratory drug susceptibility testing. By finding isolates with (near-)identical genomic variation, five major clusters containing a total of 114 isolates were identified: all containing either L1 or L4 isolates with at least MDR-TB resistance and spanning multiple years of collection. Closer inspection of clusters revealed transmission in prisons, some involving isolates with XDR-TB, and mutations linked to third-line drug bedaquiline. We have also identified previously unreported mutations linked to resistance for isoniazid, rifampicin, ethambutol, and fluoroquinolones. Overall, this study provides important insights into the genetic diversity, transmission and circulating drug resistance mutations of M. tuberculosis in the Philippines, thereby informing clinical and surveillance decision-making, which is increasingly using NGS platforms.

A randomized, controlled dose-finding Phase II study of the M72/AS01 candidate tuberculosis vaccine in healthy PPD-positive adults.

PURPOSE: In this dose-finding Phase II study (NCT00621322), we evaluated the safety and immunogenicity of different formulations of the candidate tuberculosis vaccine containing the M72 antigen (10/20/40 µg doses) and the liposome-based AS01 Adjuvant System. We aimed to select the lowest-dose combination of M72 and AS01 that was clinically well tolerated with immunogenicity comparable to that of the previously tested M72/AS01B (40 µg) candidate vaccine. METHODS: Healthy PPD-positive (induration 3-10 mm) adults (18-45 years) in The Philippines were randomized (4:4:4:4:1:1) to receive 2 injections, 1 month apart, of M72/AS01B (40 µg), M72/AS01E (10 µg), M72/AS01E (20 µg), M72/AS02D (10 µg), M72/Saline (40 µg) or AS01B alone, and were followed up for 6 months. AS01E and AS02D contain half the quantities of the immunostimulants present in AS01B. AS02D is an oil-in-water emulsion. Vaccine selection was based on the CD4(+) T-cell responses at 1 month post vaccination. RESULTS: All formulations had a clinically acceptable safety profile with no vaccine-related serious adverse events reported. Two vaccinations of each adjuvanted M72 vaccine induced M72-specific CD4(+) T-cell and humoral responses persisting at 6 months post vaccination. No responses were observed with AS01B alone. One month post second vaccination, CD4(+) T-cell responses induced by each of the three M72/AS01 vaccine formulations were of comparable magnitudes, and all were significantly higher than those induced by M72/AS02D (10 µg) and M72/Saline. CONCLUSIONS: The formulation with the lowest antigen and adjuvant dose, M72/AS01E (10 µg), fulfilled our pre-defined selection criteria and has been selected for further clinical development.

A molecular epidemiologic analysis of Mycobacterium tuberculosis among Filipino patients in a suburban community in the Philippines.

BACKGROUND: The Philippines is designated as one of the high tuberculosis (TB) burden countries by WHO. We conducted a molecular epidemiologic analysis of Mycobacterium tuberculosis isolates collected from patients consulting at the health clinics in the city of Santa Rosa, Laguna, a suburban community in the Philippines. METHODS: A total of 116 M. tuberculosis isolates were characterized and genotyped using spoligotyping and 15 loci of variable number of tandem repeats of mycobacterial interspersed repetitive units (15 MIRU-VNTR). The strains were then compared with the international spoligotyping database (SpolDB4). Cluster analyses were done using 15 MIRU-VNTR and spoligotyping. RESULTS: Majority of the patients with pulmonary tuberculosis were young (18-29 year age group at 41.4%) and male (62.1%). 86/116 (74.1%) were sputum-smear positive and 43/116 (37.1%) had severe pulmonary tuberculosis. When the genotyping results were compared to the SpolDB4, there were 10 identified Spoligo-International-Types (SITs) with SIT 19 as the predominant SIT (89/116, 76.7%). 10 out of 116 (8.6%) did not match any SIT in the SpolDB4. The distribution of strains according to major M. tuberculosis clades was as follows: EAI2_Manilla (101/116, 87.1%; U 2/116, 1.7%; LAM2 1/116, 0.9%; EAI3_Ind 1/116, 0.9%; MANU2 1/116, 0.9%. Using univariate and multivariate analysis, there was no significant association shown between the EAI2_Manilla clade and SIT with patient characteristics such as sex and age groups as well as bacillary load based on sputum-smear positivity and severity of pulmonary tuberculosis. Using logistic regression, no patient characteristic, as well as bacillary load or severity of TB, were significant predictors for clade or SIT. Based on the molecular typing method used, spoligotyping identified 4 clusters and 20 genotypes (16 unique strains) with a Hunter-Gaston discrimination index (HGDI) of 0.409. 15 MIRU-VNTR identified 16 clusters and 69 genotypes (53 unique strains) with an HGDI of 0.960. The combination of spoligotyping and 15 MIRU-VNTR identified 11 clusters and 79 genotypes (68 unique strains) with the highest HGDI at 0.970. High case rate of TB among young people in this community suggests the high transmission rate of infection. However, in the absence of significant association between clustering and age, the interpretation of observed high cluster rate warrants caution, and requires further molecular and epidemiological observation. CONCLUSION: This is the first molecular epidemiology study to show the distribution of genotypes of the M. tuberculosis strains, systematically and prospectively sampled, of the patient population in a suburban community in the Philippines. The combination of spoligotyping and 15 MIRU-VNTR identified 11 clusters and 79 genotypes (68 unique strains) with the highest HGDI at 0.970. High case rate of TB among young people in this community suggests the high transmission of infection. However, in the absence of significant association between clustering and age, the interpretation of observed high cluster rate warrants caution, and requires further molecular and epidemiological observation.

Effect of body image perception and skin-lightening practices on mental health of Filipino emerging adults: a mixed-methods approach protocol.

INTRODUCTION: The rampant distribution of idealised images on the internet may lead the general public to improve their body appearance in a way that is sometimes excessive, compulsive or detrimental to other aspects of their lives. There is a decreasing appreciation of body image among emerging adults and an increasing trend on skin-lightening practices linked with psychological distress. This protocol describes the mixed-method approach to assess the relationships among body image perception, skin-lightening practices and mental well-being of Filipino emerging adults and determine the factors that influence them. METHODS AND ANALYSIS: An explanatory sequential mixed-method approach will be used. A cross-sectional study design will involve an online self-administered questionnaire of 1258 participants, while a case study design will involve in-depth interviews with 25 participants. Data analysis will use generalised linear models and structural equation modelling with a Bayesian network for the quantitative data. Moreover, the qualitative data will use an inductive approach in thematic analysis. A contiguous narrative approach will integrate the quantitative and qualitative data. ETHICS AND DISSEMINATION: The University of the Philippines Manila Review Ethics Board has approved this protocol (UPMREB 2022-0407-01). The study results will be disseminated through peer-reviewed articles and conference presentations.

Molecular characterization of drug-resistant Mycobacterium tuberculosis among Filipino patients derived from the national tuberculosis prevalence survey Philippines 2016.

Tuberculosis, caused by Mycobacterium tuberculosis, remains a high burden disease and leading cause of mortality in the Philippines. Understanding the genetic diversity of M. tuberculosis strains in the population, including those that are multi-drug resistant (MDR), will aid in formulating strategies for effective TB control and prevention. By whole genome sequencing of M. tuberculosis isolates (n = 100) from patients of the Philippine 2016 National Tuberculosis Prevalence Survey, we sought to provide a baseline assessment of the genotypic and phylogenetic characteristics of the isolates. The majority (96/100) of the isolates were EAI2-Manila strain-type (lineage 1), with one Lineage 2 (Beijing), one Lineage 3 (CAS1), and two Lineage 4 (LAM9) strains. The EAI2-Manila clade was not significantly associated with patient's phenotypic and in silico drug resistance profile. Five (5/6) MDR-TB isolates predicted by in silico profiling were concordant with phenotypic drug resistance profile. Twenty-one mutations were identified in nine drug resistance-related genes, all of which have been reported in previous studies. Overall, the results from this study contribute to the growing data on the molecular characteristics of Philippine M. tuberculosis isolates, which can help in developing tools for rapid diagnosis of TB in the country, and thereby reducing the high burden of disease.

Spectrophotometric evaluation of color alterations with a new dental bleaching product in patients wearing orthodontic appliances.

INTRODUCTION: Our objective was to assess the effectiveness of a new bleaching agent (8% hydrogen peroxide) used in patients wearing fixed orthodontic appliances. METHODS: Six anterior maxillary teeth of 40 patients aged 18 to 40 years were assessed. The patients were divided into 2 groups (20 in each group): in group A, the patients used the bleaching agent during orthodontic treatment; in group B, the patients used the bleaching agent after orthodontic treatment. For each group, a record of the initial tooth shade was taken with a polyvinyl siloxane matrix and a spectrophotometer. The groups had bleaching treatments with an 8% hydrogen peroxide product (Opalescence Treswhite Ortho, Ultradent, Opal Orthodontics, South Jordan, Utah) for 10 days in 45-minute sessions. For group A, the treatment was performed 10 days before finishing orthodontic treatment; at the end of the treatment, a new tooth shade record was taken with the polyvinyl siloxane matrix and a spectrophotometer. The subjects in group B had the same bleaching protocol after their brackets were removed. RESULTS: It was observed that, for the group without brackets, the color alteration ranged from 3 to 12 (mean, 8; median, 8.3); for the group with brackets, the range was between 4 and 13 (mean, 9; median, 8.5), indicating significant tooth bleaching in both groups with and without brackets (P >0.05). CONCLUSIONS: Opalescence Treswhite Ortho was shown to be an efficient bleaching agent in patients wearing fixed orthodontic appliances.

Detection and Genome Sequencing of SARS-CoV-2 Variants Belonging to the B.1.1.7 Lineage in the Philippines.

We report the sequencing and detection of 36 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) samples containing lineage-defining mutations specific to viruses belonging to the B.1.1.7 lineage in the Philippines.

Nonoperative Management of Multiple Penetrating Cardiac and Colon Wounds from a Shotgun: A Case Report and Literature Review.

INTRODUCTION: Surgery for cardiac trauma is considered fatal and for wounds of the colon by associated sepsis is normally considered; however, conservative management of many traumatic lesions of different injured organs has progressed over the years. PRESENTATION OF THE CASE: A 65-year-old male patient presented with multiple shotgun wounds on the left upper limb, thorax, and abdomen. On evaluation, he was hemodynamically stable with normal sinus rhythm and normal blood pressure, no dyspnea, or abdominal pain. Computed tomography (CT) scan of the chest shows hematoma around the aorta without injury to the blood vessel wall with an intramyocardial projectile without pericardial effusion. CT scan of the abdomen showed pellets in the transverse colon and descending colon endoluminal without extravasation of contrast medium or intra-abdominal fluid. The patient remains hemodynamically stable, and nonsurgical procedure was established. DISCUSSION: Patients with asymptomatic intramyocardial projectiles can be safely managed without surgery. Nonsurgical management is only possible in asymptomatic patients with trauma of the colon through close surveillance and with very selective patients since standard management is surgery. CONCLUSION: Nonsurgical management of cardiac trauma, as well as colon penetrating trauma, can be performed in carefully selected patients with proper clinical follow-up, imaging, and laboratory studies.

[Traumatic diaphragmatic rupture. A review of seven cases]. / Rotura traumática del diafragma. Revisión de siete casos.

BACKGROUND: Traumatic diaphragmatic rupture is an infrequent lesion usually found in polytrauma cases or after violent attacks. Patients are usually males between 20 and 50 years old, and car accidents are the main causes in Europe. Preoperative diagnosis must be based on a high level of suspicion and appropriate radiological explorations. Diagnostic delay is associated with high morbidity and mortality and early surgical treatment is required for successful management. We undertook this study to analyze the epidemiology of diaphragmatic rupture and to report our results in the diagnosis and treatment of this injury. METHODS: We present seven cases from 1999 through 2005. We analyzed the reasons for admission, signs and symptoms, diagnostic approach, associated lesions, treatment and course. CONCLUSION: Diagnosis of diaphragmatic rupture is difficult due to changeable symptomatology; nevertheless, it must be considered in all polytraumatized patients. Computerized tomography is the radiological exploration of choice and the most suitable surgical approach is laparotomy.

Developing the Philippines as a Global Hub for Disaster Risk Reduction - A Health Research Initiative as Presented at the 10th Philippine National Health Research System Week Celebration.

The recent Philippine National Health Research System (PNHRS) Week Celebration highlighted the growing commitment to Disaster Risk Reduction (DRR) in the Philippines. The event was lead by the Philippine Council for Health Research and Development of the Department of Science and Technology and the Department of Health, and saw the participation of national and international experts in DRR, and numerous research consortia from all over the Philippines. With a central focus on the Sendai Framework for Disaster Risk Reduction, the DRR related events recognised the significant disaster risks faced in the Philippines. They also illustrated the Philippine strengths and experience in DRR. Key innovations in science and technology showcased at the conference include the web-base hazard mapping applications 'Project NOAH' and 'FaultFinder'. Other notable innovations include 'Surveillance in Post Extreme Emergencies and Disasters' (SPEED) which monitors potential outbreaks through a syndromic reporting system. Three areas noted for further development in DRR science and technology included: integrated national hazard assessment, strengthened collaboration, and improved documentation. Finally, the event saw the proposal to develop the Philippines into a global hub for DRR. The combination of the risk profile of the Philippines, established national structures and experience in DRR, as well as scientific and technological innovation in this field are potential factors that could position the Philippines as a future global leader in DRR. The purpose of this article is to formally document the key messages of the DRR-related events of the PNHRS Week Celebration.

A look at the ASEAN-NDI: building a regional health R&D innovation network.

Globally, there are growing efforts to address diseases through the advancement in health research and development (R&D), strengthening of regional cooperation in science and technology (particularly on product discovery and development), and implementation of the World Health Assembly Resolution 61.21 (WHA61.21) on the Global Strategy and Plan of Action on Public Health, Innovation, and Intellectual Property (GSPA-PHI). As such, the Association of Southeast Asian Nations (ASEAN) is responding to this through the establishment of the ASEAN-Network for Drugs, Diagnostics, Vaccines, and Traditional Medicines Innovation (ASEAN-NDI). This is important in the ASEAN considering that infectious tropical diseases remain prevalent, emerging, and reemerging in the region. This paper looks into the evolution of the ASEAN-NDI from its inception in 2009, to how it is at present, and its plans to mitigate public health problems regionally and even globally.

Enfoque del manejo de cuerpos extraños colorrectales: revisión de la literatura / Literature Review of Management of Colorectal Foreign Bodies

Resumen La presentación de pacientes con cuerpos extraños a nivel rectal no es poco frecuente; sin embargo, hay pocas estadísticas sobre la epidemiología de esta entidad. La mayor parte de la literatura publicada hace mención a reporte de casos o series de casos. Los cuerpos extraños rectales son insertados de forma intencional o no intencional, y constituyen un reto diagnóstico y terapéutico para el médico; por lo que el médico a cargo requiere de la habilidad y conocimiento para extraer objetos de diferentes formas y tamaños. Los cuerpos extraños rectales son generalmente observados en la población adulta; en relación con la estimulación erótica o asalto sexual. Adicionalmente, algunos cuerpos extraños pueden ser ingeridos ocasionalmente, pasando a través del tracto gastrointestinal y alojándose en el recto, aunque esta situación es la menos común; en especial en pacientes con enfermedades mentales, trastornos visuales, alcohólicos o usuarios de prótesis dentales. La finalidad de esta revisión es establecer unas pautas de manejo y dar a conocer un algoritmo para el enfoque de los cuerpos extraños colorrectales.

Abstract Patients with foreign bodies in their rectums are not uncommon, but statistics on the epidemiology of this entity are scarce. Most of the literature published consists of case reports or case series. Foreign rectal bodies, whether inserted intentionally or unintentionally, constitute a diagnostic and therapeutic challenge for physicians who need skill and knowledge to extract objects of different shapes and sizes. Foreign rectal bodies are generally observed in the adult population in relation to erotic stimulation or sexual assault. Occasionally, foreign bodies are ingested and pass through the gastrointestinal tract to lodge in the rectum. Although this situation is the least common, it does occur, especially in patients with mental illnesses, visual disorders, or alcoholism and among users of dental prostheses. The purpose of this review is to establish management guidelines and to present an algorithm for the approach to colorectal foreign bodies.

Cirugía gástrica laparoendoscópica cooperativa / Laparo-endoscopic cooperative gastric surgery

Antecedentes: La cirugía gástrica cooperativa utliza vías simultáneas intraluminal peroral e intraperitoneal transabdominal para localizar y tratar, en tempo real, lesiones de dificil manejo con procedimientos convencionales. Su objetivo es resecar lesiones con técnicas videoasistidas, simultáneas, conservando tejido y funcionalidad, con los beneficios de la cirugía mínimamente invasiva. Objetivos: Describir nuestra experiencia en la realización de procedimientos cooperativos gástricos en el Instituto Nacional de Cancerología. Material y métodos: Revisión prospectiva de una base datos retrospectiva. Análisis descriptivo de pacientes en quienes se realizaron procedimientos gástricos cooperativos en el Instituto Nacional de Cancerología de Bogotá, Colombia, intervenidos entre octubre de 2012 y noviembre de 2016. Resultados: Se realizaron 16 procedimientos gástricos laparoendoscópicos: ocho de las 16 lesiones resecadas fueron subepiteliales, 4 intervenciones se indicaron para ampliación de márgenes posterior a resección endoscópica, 2 fueron lesiones epiteliales y 2 procedimientos se realizaron para control del sangrado con intención paliativa. Catorce procedimientos fueron de tpo exogástrico, 1 intragástrico y 1 transgástrico. El tempo quirúrgico promedio fue de 91 minutos, con pérdidas sanguíneas en promedio de 42 mL con bordes de resección negativos en todos los casos. El tempo promedio de hospitalización fue de 4 días. La supervivencia libre de enfermedad a 22 meses fue del 100%. Conclusiones: Los resultados de nuestro estudio muestran que la cirugía gástrica cooperativa es una técnica segura, factible, con tempos quirúrgicos aceptables y sangrados mínimos en pacientes con comorbilidades y sin ellas, conservando los principios oncológicos y de la cirugía mínimamente invasiva en el tratamiento de las neoplasias gástricas.

Background: cooperative gastric surgery uses simultaneous, intraluminal peroral and intraperitoneal trans-abdominal pathways to localize and treat, in real tme, dificult tumors with conventonal proce-dures. The aim is to resect lesions of diferent etology with video assited techniques, simultaneous, preserving tssue and functonality, with the benefts of minimally invasive surgery. Objective: the aim of our study was describe our experience in cooperative gastric procedures at the Natonal Cancer Institute in Bogotá, Colombia. Materials and methods: prospective review of a retrospective database. Descriptive analysis of pa-tents in whom cooperative gastric procedures were performed at the Natonal Cancer Institute of Bogotá, Colombia, between October 2012 and November 2016. Results: sixteen laparoscopic endoscopic cooperative procedures were performed; eight of 16 resec-ted tumors were subepithelial; four cases were done for resecton of previous positive margins, two epithelial lesions and two for bleeding and palliative control. Fourteen procedures were exogastric, 1 intragastric and 1 transgastric. The operative tme was 91 minutes, the average bleeding was 42 cc and negative margins were present in all cases. The mean hospital stay was 4 days. Conclusions: Our study shows that laparoscopic endoscopic cooperative surgery is a safe and feasible technique with acceptable operative tmes and minimal bleeding in patents with and without comorbidites, preserving the oncological and minimally invasive principles in the treatment of gastric neoplasms.

Hernia abdominal traumática / Traumatic abdominal hernia

Las hernias abdominales traumáticas son un tipo de hernias adquiridas, secundarias a traumatismo cerrado. Se reportan dos casos de este tipo de lesiones, uno de ellos con lesión abdominal significativa asociada. En uno de los casos, se corrigió el defecto por planos y fijación de malla de polipropileno por encima de la fascia; el otro fue corregido con malla por abordaje laparoscópico. En ambos casos, el periodo posoperatorio transcurrió sin complicaciones. Se presenta una revisión de la literatura.

Traumatic abdominal wall hernias are a type of acquired hernias secondary to blunt trauma. We report two cases of such hernias, one of them with significant intra-abdominal injury. One wall defect was repaired in layers and fixation of polypropylene mesh over the fascia. The other case was repaired by laparoscopy. Postoperative course was uneventful. The latest literature is reviewed. With this literature review and case report we hope to augment the knowledge on traumatic abdominal wall hernias, hopefully leading to early diagnosis and treatment.

Characterization of the Manila family of Mycobacterium tuberculosis.

Forty-eight Mycobacterium tuberculosis strains were obtained from patients living in metropolitan Manila, Republic of the Philippines. Three molecular typing methods, IS6110 restriction fragment length polymorphism, spoligotyping, and DNA sequencing of the oxyR, gyrA, and katG loci, established that these strains have restricted diversity and are members of a related genetic group of organisms. Comparison of the DNA fingerprint patterns with those in international databases confirmed the uniqueness of this group of isolates, which we designate the Manila family of M. tuberculosis.

Rotura traumática del diafragma: revisión de siete casos / Traumatic diaphragmatic rupture: a review of seven cases

Introducción: la rotura traumática del diafragma es una lesión infrecuente que aparece en politraumatismos o agresiones. Predomina en los varones entre 20 y 50 años de edad, siendo los accidentes de tráfico la principal causa en Europa. El diagnóstico preoperatorio requiere alto nivel de sospecha junto con las adecuadas exploraciones radiológicas. El retraso diagnóstico se asocia con elevada morbilidad y mortalidad, constituyendo la intervención quirúrgica inmediata un factor determinante para el éxito en el tratamiento de estos pacientes. El objetivo de este informe fue analizar la incidencia y epidemiología de la rotura traumática del diafragma en nuestro medio, y exponer nuestros resultados en el diagnóstico y tratamiento de esta lesión. Material y métodos: presentamos siete casos correspondientes al periodo 1999-2005 y analizamos el motivo de ingreso, la clínica, las formas de diagnóstico, las lesiones asociadas, el tratamiento y la evolución. Conclusiones: el diagnóstico de rotura diafragmática es difícil debido a su baja frecuencia y a su sintomatología variable, no obstante, debe ser considerado en todo paciente politraumatizado. La tomografía helicoidal es la exploración radiológica de elección y la vía de abordaje más adecuada es la laparotomía media.

BACKGROUND: Traumatic diaphragmatic rupture is an infrequent lesion usually found in polytrauma cases or after violent attacks. Patients are usually males between 20 and 50 years old, and car accidents are the main causes in Europe. Preoperative diagnosis must be based on a high level of suspicion and appropriate radiological explorations. Diagnostic delay is associated with high morbidity and mortality and early surgical treatment is required for successful management. We undertook this study to analyze the epidemiology of diaphragmatic rupture and to report our results in the diagnosis and treatment of this injury. METHODS: We present seven cases from 1999 through 2005. We analyzed the reasons for admission, signs and symptoms, diagnostic approach, associated lesions, treatment and course. CONCLUSION: Diagnosis of diaphragmatic rupture is difficult due to changeable symptomatology; nevertheless, it must be considered in all polytraumatized patients. Computerized tomography is the radiological exploration of choice and the most suitable surgical approach is laparotomy.