Uso potencial de residuos agroindustriales como fuente de compuestos fenólicos con actividad biológica

Los compuestos fenólicos poseen propiedades bioactivas de interés en la Medicina. Investigaciones actuales se enfocan en la búsqueda de nuevas fuentes de este tipo de compuestos. Varios estudios se han propuesto recuperar, caracterizar e identificar compuestos fenólicos a partir de residuos agroindustriales buscando en ellos diversas actividades biológicas. La presente investigación se desarrolló con el objetivo de describir el uso potencial de residuos agroindustriales como una fuente de compuestos fenólicos con actividad biológica y su uso en la Medicina. Los residuos agroindustriales poseen un elevado potencial como novedosa fuente de compuestos fenólicos con actividad biológica, empleables en la farmacéutica, industria alimentaria y cosmética. Entre sus aplicaciones se encuentran las de antioxidante, antiinflamatorio, antimicrobiano y la actividad antiproliferativa. Varios de los residuos agroindustriales provienen de productos cultivables en Ecuador, de ahí que constituya una oportunidad a explotar en la industria nacional. Los estudios en Ecuador sobre el aprovechamiento de residuos agroindustriales se enfocan en la obtención de biocombustibles, bioplásticos y productos de alimentación animal, por lo que la búsqueda de compuestos bioactivos a partir de nuevas fuentes aún es un campo incipiente.

Phenolic compounds have bioactive properties of interest in Medicine. Current research focuses on the search for new sources of this type of compounds. Several studies have proposed recovering, characterizing and identifying phenolic compounds from agroindustrial waste, searching for various biological activities in them. The present research was developed with the objective of describing the potential use of agroindustrial waste as a source of phenolic compounds with biological activity and their use in Medicine. Agroindustrial waste has a high potential as a novel source of phenolic compounds with biological activity, which can be used in the pharmaceutical, food and cosmetic industries. Among its applications are antioxidant, anti-inflammatory, antimicrobial and antiproliferative activity. Several of the agroindustrial waste come from cultivable products in Ecuador, hence it constitutes an opportunity to be exploited in the national industry. Studies in Ecuador on the use of agroindustrial waste focus on obtaining biofuels, bioplastics and animal feed products, so the search for bioactive compounds from new sources is still an incipient field.

Tratamientos y bioterapias para COVID-19 / Therapeutics and biotherapies for covid-19

INTRODUCCIÓN: Un nuevo brote de coronavirus surgió en 2019 en Wuhan, China, causando conmoción en el sistema sanitario de todo el mundo; el Comité Internacional de Taxonomía de Virus lo denominó SARS-CoV-2, agente causante de la enfermedad COVID-19.El espectro de gravedad de la enfermedad es muy amplio: la mayoría de los pacientes no presentan gravedad, pero otros pueden desarrollar neumonías, y la insuficiencia respiratoria aguda es la causa más frecuente de mortalidad. Objetivo: analizar y desarrollar las distintas alternativas terapéuticas aportadas por la Biotecnología para tratar los síntomas de aquellos pacientes con COVID-19. Metodología: se realizó una revisión de la bibliografía disponible, a partir de enero de 2020 en PubMed, acerca de los tratamientos que se encuentran aún en ensayos clínicos y aquellos que cuentan con aprobación bajo uso de emergencia para la enfermedad COVID-19. También se realizaron búsquedas a través de Google y Google Académico para publicaciones de organismos de Salud en referencia a políticas de salud establecidas para la terapéutica durante dicha pandemia. Resultados: este trabajo aborda las nuevas alternativas terapéuticas para COVID-19 derivadas de la Biotecnología, que se encuentran tanto en uso como en etapas de ensayos clínicos comprendidos dentro del segmento de los biofármacos y las bioterapias. Se incluye un breve resumen del estatus regulatorio de entidades de salud, el mecanismo de acción de dichas terapias y características generales de cada uno. Se incluyen novedosas bioterapias que se empezaron a implementar para afrontar la pandemia. Conclusiones: la pandemia de coronavirus está poniendo a prueba el sistema sanitario internacional, para brindar soluciones tanto desde el diagnóstico y prevención como para el tratamiento de la población a fin de disminuir la mortalidad. Esto incluyó, obviamente también, al área de la Biotecnología aplicada a la salud, que ha aportado en los tres aspectos mencionados; el presente trabajo se centra en las respuestas de tipo terapéutico que ha brindado y que están comercializadas o en fases clínicas. (AU)

INTRODUCTION: A new coronavirus outbreak emerged in 2019 in Wuhan, China, causing a shock to the healthcare system around the world; the International Committee on Taxonomy of Viruses named it SARS-CoV- 2, the infectious agent of the COVID-19 disease. The spectrum of severity of the disease is very wide, most patients are not serious, but others can develop pneumonia, with acute respiratory failure being the most frequent cause of mortality. Objective: to analyze and develop the different therapeutic alternatives provided by Biotechnology dedicated to Health, to treat the symptoms of those COVID-19 patients who require it, and thus reduce mortality.Methodology: a review of the available literature from January 2020 in PubMed of the treatments that are still in clinical trials and those that have been approved under emergency use for the disease COVID-19 was performed. Searches were also carried out through Google and Google Scholar for publications of Health organizations in reference to health policies established for therapeutics during the mentioned pandemic. Results: this work addresses the new therapeutic alternatives derived from Biotechnology, which are both in use and in stages of clinical trials, to treat patients who developed COVID-19 included within the segment of biopharmaceuticals and biotherapies. A brief summary of the regulatory status of health entities, the mechanism of action of said therapies and general characteristics of each one is included. Innovative biotherapies that began to be implemented to face the pandemic are included. Conclusions: The coronavirus pandemic has driven the international health system to the test, to provide solutions both from the diagnosis, prevention and treatment of the population to reduce the mortality of patients. This obviously also included the area of Biotechnology applied to health, which has contributed in the three aspects mentioned. The present work focuses on the therapeutic responses that it has provided and that are commercialized or in clinical phases. (AU)

Biopharmaceuticals for prevention of COVID-19: A scoping review

The COVID-19 epidemic caused by SARS-CoV-2 virus has turned into a worldwide pandemic. Therefore, health officials all around the world have strived for developing efficient preventive and treatment methods to deal with this global crisis. Amongst them, monoclonal antibodies, anti-TNFs, and convalescent plasma appear to be effective against this disease. In addition, clinical trials are currently being conducted for viral targeting vaccines. This review summarizes major advances using biopharmaceuticals in the treatment and prevention strategies against COVID-19 that have occurred in the global medicinal system from its introduction until March 2022.

Launching a CDMO in Brazil aiming to develop biopharmaceuticals for clinical trials

The innovation timeline is expensive, risky, competitive, time-consuming, and labor-intensive. In order to overcome such challenges and optimize financial resources, pharmaceutical companies nowadays hire contract development and manufacturing organizations (CDMO) to help them. Based on the experience acquired first from the development of two biopharmaceuticals, the Heterologous Fibrin Sealant and the Apilic Antivenom, and more recently, during their respective clinical trials; the Center for the Study of Venoms and Venomous Animals (CEVAP) proposed to the Ministry of Health the creation of the first Brazilian CDMO. This groundbreaking venture will assist in converting a candidate molecule - from its discovery, proof of concept, product development, up to pilot batch production - into a product. The CDMO impact and legacy will be immense, offering service provision to the public and private sector by producing validated samples for clinical trials and academic training on translational research for those seeking a position in pharmaceutical industries and manufacturing platforms.(AU)

Decline in Public Spending on Biopharmaceutics in Brazil

Abstract Biopharmaceuticals, mainly monoclonal antibodies, and fusion proteins are drugs that have gained notoriety in the treatment of various chronic and inflammatory diseases and have high prices. The study aimed to verify which monoclonal antibodies and fusion proteins were most incorporated into the Unified Health System (SUS), which therapeutic indication most benefited from them and to analyze public spending on these biopharmaceuticals from January 2012 to September 2019. This study performed a qualitative and quantitative analysis of biopharmaceuticals incorporated by SUS. The data were collected on the websites of CONITEC and the Health Price Bank. The results demonstrated that subcutaneous adalimumab was most frequently incorporated, and the most requested therapeutic indication was rheumatoid arthritis. Public spending on biopharmaceuticals exceeded R$ 28 billion (more than US$ 140 billion). However, a downward trend was confirmed (-266.7%) in the period evaluated. Despite the increase in demand and public spending on biologics in general, in Brazil and worldwide, the results of this research show that there was a drop in public spending on the biopharmaceuticals studied in the last seven years.

Endophthalmitis caused by Bacteroides fragilis after pars plana vitrectomy and treatment approach

Rationale: Endophthalmitis is an uncommon but serious ocular infection often resulting in probable visual loss. Bacteroides fragilis is a rare cause of endophthalmitis. Patient concerns: A 46-year-old male patient complained of eye pain and low vision after pars plana vitrectomy. Diagnosis: Bacteroides fragilis endophthalmitis after pars plana vitrectomy was diagnosed. Interventions: Pars plana vitrectomy and silicone oil implantation were performed. Outcomes: Early treatment and choice of tamponade in endophthalmitis after pars plana vitrectomy may possibly prevent evisceration and progression of endophthalmitis. Lessons: Bacteroides fragilis can be seen in cases of endophthalmitis after pars plana vitrectomy.

An immunoglobulin y that specifically binds to an in silico-predicted unique epitope of Zika virus non-structural 1 antigen

Objective: To identify unique immunogenic epitopes of Zika virus non-structural 1 (NS1) antigen and produce immunoglobulin Y (IgY) for potential use in he diagnosis of of Zika virus infection. Methods: Immunogenic epitopes were identified using in silico B-cell epitope prediction. A synthetic peptide analog of the predicted epitope was used to induce antipeptide IgY production in hens which was purified using affinity chromatography. Presence of purified IgY and its binding specificity were performed by gel electrophoresis and ELISA, respectively. Results: Out of the nine continuous epitopes identified, the sequence at position 193-208 (LKVREDYSLECDPAVI) was selected and used to produce anti-peptide IgY. The produced IgY was found to bind to the synthetic analog of the Zika virus NS1 immunogenic epitope but not to other flaviviruses and random peptides from other pathogens. Conclusions: In this study, we identified an immunogenic epitope unique to Zika virus that can be used to develop a serodiagnostic tool that specifically detect Zika virus infection.

Spatiotemporal heterogeneity of schistosomiasis in mainland China: Evidence from a multi-stage continuous downscaling sentinel monitoring

Objective: To determine the spatiotemporal distribution of Schistosoma (S.) japonicum infections in humans, livestock, and Oncomelania (O.) hupensis across the endemic foci of China. Methods: Based on multi-stage continuous downscaling of sentinel monitoring, county-based schistosomiasis surveillance data were captured from the national schistosomiasis surveillance sites of China from 2005 to 2019. The data included S. japonicum infections in humans, livestock, and O. hupensis. The spatiotemporal trends for schistosomiasis were detected using a Joinpoint regression model, with a standard deviational ellipse (SDE) tool, which determined the central tendency and dispersion in the spatial distribution of schistosomiasis. Further, more spatiotemporal clusters of S. japonicum infections in humans, livestock, and O. hupensis were evaluated by the Poisson model. Results: The prevalence of S. japonicum human infections decreased from 2.06% to zero based on data of the national schistosomiasis surveillance sites of China from 2005 to 2019, with a reduction from 9.42% to zero for the prevalence of S. japonicum infections in livestock, and from 0.26% to zero for the prevalence of S. japonicum infections in O. hupensis. Analysis using an SDE tool showed that schistosomiasis-affected regions were reduced yearly from 2005 to 2014 in the endemic provinces of Hunan, Hubei, Jiangxi, and Anhui, as well as in the Poyang and Dongting Lake regions. Poisson model revealed 11 clusters of S. japonicum human infections, six clusters of S. japonicum infections in livestock, and nine clusters of S. japonicum infections in O. hupensis. The clusters of human infection were highly consistent with clusters of S. japonicum infections in livestock and O. hupensis. They were in the 5 provinces of Hunan, Hubei, Jiangxi, Anhui, and Jiangsu, as well as along the middle and lower reaches of the Yangtze River. Humans, livestock, and O. hupensis infections with S. japonicum were mainly concentrated in the north of the Hunan Province, south of the Hubei Province, north of the Jiangxi Province, and southwestern portion of Anhui Province. In the 2 mountainous provinces of Sichuan and Yunnan, human, livestock, and O. hupensis infections with S. japonicum were mainly concentrated in the northwestern portion of the Yunnan Province, the Daliangshan area in the south of Sichuan Province, and the hilly regions in the middle of Sichuan Province. Conclusions: A remarkable decline in the disease prevalence of S. japonicum infection was observed in endemic schistosomiasis in China between 2005 and 2019. However, there remains a long-term risk of transmission in local areas, with the highest-risk areas primarily in Poyang Lake and Dongting Lake regions, requiring to focus on vigilance against the rebound of the epidemic. Development of high-sensitivity detection methods and integrating the transmission links such as human and livestock infection, wild animal infection, and O. hupensis into the surveillance-response system will ensure the elimination of schistosomiasis in China by 2030.

Antibiotic resistance pattern of Pseudomonas aeruginosa wound isolates among Chinese burn patients: A systematic review and meta analysis

Objective: To investigate the resistance profiles to antimicrobial agents of wound-isolated Pseudomonas (P.) aeruginosa among Chinese burn patients. Methods: Electronic databases and manual search were used to identify eligible studies published since 2010. The objectives were pooled resistance rates for eleven common antimicrobial agents, estimated by a random-effects model. Subgroup analyses were conducted by stratifying the studies into three four-year periods based on year of isolation. Results: A total of 35 studies were included. Gentamicin had the highest pooled resistance rate (56%, 95% CI 48%-64%), while meropenem had the lowest pooled resistance rate (29%, 95% CI 20%-40%). There was an increasing trend of resistance to common antimicrobial agents of wound-isolated P. aeruginosa over a span of twelve years (2009-2020). There remained the highest risk of gentamicin resistance over time in China. Subgroup analyses indicated significantly higher resistances to ceftazidime and levofloxacin from 2017 to 2020. Conclusions: Enhanced resistance to common antimicrobial agents in wound-isolated P. aeruginosa presents a challenge in burn wound management in mainland China. Effective stewardship programs should be established based on corresponding resistance profiles, thereby optimizing treatment options for hospitalized burn patients.

Liposomes as immunological adjuvants and delivery systems in the development of tuberculosis vaccine: A review

Liposomes are phospholipid bilayer vesicles, which are biocompatible, biodegradable and nontoxic vehicles suitable for numerous drug and gene delivery applications. In this review, we discuss the prospect of using liposome technology in the development of a vaccine for tuberculosis. Tuberculosis remains an important health problem that requires the development of an effective vaccine, especially since the only approved vaccine for it continues to be the Bacille Calmette-Geurin (BCG) one developed 100 years ago. This review focuses on the different applications of liposomes toward achieving this goal. Numerous liposomal formulations showing prospect in the research stage and in clinical trials are discussed.

Furuncular myiasis by Wohlfahrtia magnifica (Diptera: Sarcophagidae) in a healthy child

Rationale: Human myiasis is the invasion of tissue or organs by fly larvae. This could be obligatory, facultative, or accidental. Patient concerns: A 4-year-old Saudi boy complained of fever over the past three days with multiple inflamed painful dermal furuncles and worms-like discharge. Diagnosis: Furuncular obligatory myiasis caused by Wohlfahrtia magnifica. Interventions: Maggots were removed for identification. The wounds were cleaned with antiseptic dressings. Topical and oral antibiotics were applied. Outcomes: Seven days later, the wounds completely healed. Lessons: Although several reports correlated human myiasis with old age, low health status, mental retardation, and low socioeconomic status, but the patient in our case was a healthy child from a family with good socioeconomic status, good hygiene, no history of diseases or mental disability, but traveled to a village where the climate is suitable for fly breeding.

Evaluation of Cuban Bacillus thuringiensis (Berliner, 1911) (Bacillales: Bacillacea) isolates with larvicidal activity against Aedes aegypti (Linnaeus, 1762) (Diptera: Culicidae)

Objective: To evaluate 11 Cuban native Bacillus (B.) thuringiensis isolates in order to select one with the best larvicidal activity against Aedes (Ae.) aegypti and low cytotoxicity. Methods: The cry and cyt genes of the isolates (A21, A51, L95, L910, M29, R84, R85, R87, R89, U81 and X48) were amplified by PCR. The influence of organic matter and NaCl on the larvicidal activity was tested by bioassays. Cytotoxicity was assayed on peritoneal macrophages of BALB/c mice. Results: The cyt1 (Aa, Ab, Ba), cyt2, cry4aA, cry4Ba, cry11 (Aa, Ba, Bb) and cry10 genes were identified in all native Cuban isolates. The larvicidal activity (LC90) of seven isolates was affected by the presence of organic matter in the water, while A21, A51, L910, R84, U81 and X48 had better LC50, LC90, LC95 than the 266/2 9-VI-98 control strain. The LC50 of two isolates was affected by the presence of NaCl and A21, A51, R85 isolate had better larvicidal activity than the 266/2 9-VI-98 control strain. In terms of toxicity against macrophages, the extracts of nine isolates were less cytotoxic than the control strains. Conclusions: Native isolate A21 had the main virulence factors against Ae. aegypti larvae, displayed a good larvicidal activity in presence of different factors related with Ae. aegypti breeding sites, and had low citotoxicity against macrophages. These results can contribute to the improvement of existing biological control strategies and the development of new biolarvicides.

Ultrastructural and enzymatic alterations in the ovary of Rhodnius prolixus infected with Trypanosoma rangeli

Objective: To investigate the morphological structure of ovarian follicular cells and biochemical parameters of both ovaries and fat bodies (sites of vitellogenesis) from Rhodnius (R.) prolixus infected with Trypanosoma (T.) rangeli. Methods: Adult virgin females of R. prolixus were fed upon a membrane apparatus containing heat-inactivated citrated rabbit blood and a suspension of T. rangeli epimastigotes (Macias strain). Females from the control group and all the males received parasitefree blood. Transmission electron microscopy was used to reveal the morphological aspects of ovarian follicle cells in both control and parasite-infected groups. Protein profile, proteolytic activities and Western blotting analyses were performed in either ovary or fat body samples of control and parasite-infected groups. Results: According to the ultrastructural data, T. rangeli infection elicited a degeneration process in the ovarian follicular cells of R. prolixus. Proteolytic assays indicated a reduction in the activity of aspartic peptidases in the ovary and fat body from parasite-infected group, while a significant increase in the cysteine peptidase activity was measured in both insect organs. Additionally, immunoblotting revealed that vitellogenin was overexpressed in the ovary of parasite-infected insects. Conclusions: T. rangeli infection seems to elicit an early programmed cell death in the ovarian follicle cells as well as induces the modulation on the activities of different peptidase classes in either ovaries or fat bodies and the overexpression of the vitellogenin in the ovary of R. prolixus.

Systematic mutational analysis of epitope-grafted ED3 immunogenicity reveals a DENV3-DENV4 bi-serospecific ED3 mutant

Objective: To identify the residue determinants of the serospecificity and sero-cross-reactivity of dengue virus (DENV) envelope protein domain 3 (ED3), which contains two major putative epitopes of DENV. Methods: We constructed ED3 from DENV3 (3ED3) and DENV4 (4ED3), and six epitope-grafted variants, where we transferred epitope 1 (L304I, K305D, V309M, and S310A) and/or epitope 2 (D383N, K384S, K387T, and N389H) of 4ED3 onto 3ED3 and vice-versa. Swiss albino mice aged 3-4 weeks were immunized against wildtype and epitope-grafted ED3 variants and anti-ED3 IgG antibody responses were determined using ELISA. Results: Mouse immunization using 3ED3 and 4ED3 generated serotype-specific antisera, as expected. Similarly, most epitopegrafted ED3s produced antisera serospecific to the template ED3 with little or no cross-recognition of ED3 of the serotype from which the epitopes were taken. These indicated that a mere grafting of the epitope was not sufficient to transfer serospecificity, contrary to our expectations. However, one epitope-grafted ED3 mutant, where epitope 1 of 3ED3 was grafted onto 4ED3 (4ED3epi1), generated antisera that was serospecific to both 4ED3 and 3ED3. Conclusions: The 4ED3epi1 is a chimeric ED3 that produces antisera possessing serospecificity to both 3ED3 and 4ED3 onto a common 4ED3 scaffold. The 4ED3epi1, therefore, provides a unique tool for analyzing serospecificity and sero-cross-reactivity in dengue. We believe that chimeric ED3 may provide a template for future recombinant ED3 possessing serospecificity of multiple DENVs onto a single scaffold and may pave a way developing tri-and/or tetravalent anti-DENV antisera.

Patterns of adverse drug reaction reporting in Ethiopia: A database analysis of spontaneous reports from 2013 to 2018

Objective: To examine the frequency and profile of spontaneous reports of adverse drug reactions (ADRs) sent to Ethiopia's pharmacovigilance (PV) database system. Methods: The descriptive and retrospective study analysed spontaneous ADR complaints reported to the PV database by healthcare professionals between 2013 and 2018. Spontaneous ADR reports that reached the PV center and met the minimum reporting criteria were identified and assessed in terms of reporting rate, patient characteristics, type of ADRs, suspected drugs, report sources, and reporters profession. Results: A total of 657 spontaneous ADR reports were filed to the PV center between 2013 and 2018. During the study period, the reporting pattern of ADRs changed dramatically. The number of reports increased from 2013 (n=12) and peaked in 2015 (n=205), and then declined from 2016 to 2018 (n=144, 142 and 65 in 2016, 2017 and 2018, respectively). Females had a higher percentage of reported cases (56.3%) than males (43.7%). The highest number of ADRs was reported in the age categories of 15-64 years (475, 72.3%), followed by 0-14 years (154, 23.4%), and 65 years and above (21, 3.2%). Pharmacists reported the majority of ADRs (81.7%), followed by health officers (7.2%), nurses (5.8%), and physicians (5.2%). Skin and subcutaneous tissue abnormalities were the most commonly reported ADRs. The anatomical therapeutic chemicals code class "anti-infective for systemic use"was the most usually suspected medication. Trimethoprim with sulfamethoxazole as a combination ADRs was the most commonly reported drug that cause ADRs (14.2%). Conclusions: The number of ADRs reported in Ethiopia was small and unpredictable compared to developed countries, indicating the performance of PV system and level of awareness of health care professionals towards ADR reporting was not satisfactory. In order to increase the frequency of spontaneous reports, more efficient PV methods and public policies must be implemented.

Sex differences in SARS-CoV-2 infections, anti-viral immunity and vaccine responses

The COVID-19 pandemic has revealed sex-based differences in anti-viral responses, with a higher rate of SARS-CoV-2 infections as well as a higher rate of morbidity and mortality in men than in women. Males and females also show disparate immune responses to COVID-19 infection, which may be important contributors to lower rates of infection, disease severity and deaths in women than in men. Here, the authors review sex differences in SARSCoV- 2 infections, anti-viral immunity and vaccine responses, putting forth the importance of sex, the underappreciated variables in vaccine response and disease infectivity.

Larvicidal activity of the pericarp extract of Garcinia mangostana against dengue vector Aedes aegypti in Sri Lanka

To assess the larvicidal activity of mangosteen (Garcinia mangostana) against larval stages of Aedes aegypti mosquitoes. Methods: A crude extract was prepared in ethanol from powdered mangosteen pericarps. A concentration gradient (0.01-4.92 g/ L) was prepared from the stock solution. Seven batches of 25 third instar larvae of Aedes aegypti were used for larval bioassays. Larval mortality rates were observed after one and 24 hours. Cholesterol and total lipid contents in 20 randomly selected dead larvae at each trial were assessed by colorimetric method. The experimental setup was repeated five times. The General Linear Model and Probit analysis were used to evaluate the relationship of mortality with cholesterol level, total lipid level and cholesterol to total lipid ratio. Results: The percentage mortalities significantly varied with different concentrations (F7,32=385.737; P<0.001). The LC50 and LC99 values were (0.041 0.006) g/L and (10.616 1.758) g/ L, respectively after 24 hours. There was no mortality recorded within the one-hour exposure time. Only the cholesterol content (F5,24=173.245; P<0.001) in larvae exposed to different concentrations denoted a significantly decreasing trend within 24- hour exposure. Larvae that were exposed to the lowest concentration (0.55 g/L) showed a higher cholesterol level (22.67 1.33) g. Conclusions: The Garcinia mangostana extract acts as an effective sterol carrier protein inhibitor that inhibits cholesterol uptake in Aedes aegypti mosquitoes. Hence, it could be explored for use as a key source for the development of an environment-friendly plantbased larvicide.

Comparison of Cox proportional hazards model, Cox proportional hazards with time-varying coefficients model, and lognormal accelerated failure time model: Application in time to event analysis of melioidosis patients

Objective: To compare the prognostic factors of mortality among melioidosis patients between lognormal accelerated failure time (AFT), Cox proportional hazards (PH), and Cox PH with timevarying coefficient (TVC) models. Methods: A retrospective study was conducted from 2014 to 2019 among 453 patients who were admitted to Hospital Sultanah Bahiyah, Kedah and Hospital Tuanku Fauziah, Perlis in Northern Malaysia due to confirmed-cultured melioidosis. The prognostic factors of mortality from melioidosis were obtained from AFT survival analysis, and Cox s models and the findings were compared by using the goodness of fit methods. The analyses were done by using Stata SE version 14.0. Results: A total of 242 patients (53.4%) survived. In this study, the median survival time of melioidosis patients was 30.0 days (95% CI 0.0-60.9). Six significant prognostic factors were identified in the Cox PH model and Cox PH-TVC model. In AFT survival analysis, a total of seven significant prognostic factors were identified. The results were found to be only a slight difference between the identified prognostic factors among the models. AFT survival showed better results compared to Cox's models, with the lowest Akaike information criteria and best fitted Cox-snell residuals. Conclusions: AFT survival analysis provides more reliable results and can be used as an alternative statistical analysis for determining the prognostic factors of mortality in melioidosis patients in certain situations.

Prevalence and risks of soil transmitted helminths among Ethiopian school children: A cross-sectional study

Objective: To assess the prevalence and associated factors of soil transmitted helminths (STHs) among Endemata primary school in North West Ethiopia, 2021. Methods: A cross-sectional study with 195 school children was conducted from May to July 2021 at Endemata primary school. The study participants were selected by using systematic random sampling technique. Stool samples were processed via direct wet mount and formol-ether concentration techniques. Data was entered by Epi-Dara version 3.1 and data analysis was done using SPSS version 20.0. Variables were considered to be statistically significant if P<0.05 at 95% confidence level. Results: The overall prevalence of STHs was 10.8% (95% CI 7.1-16.0). The prevalence of Ascaris lumbricoides, hookworm and Trichuris trichiura were 5.6% (95% CI 3.1-9.9), 3.1% (95% CI 1.3- 6.7) and 2.1% (95% CI 0.6-5.3), respectively. Grade 1-4 students were more likely to get infected with STHs as compared to grade 5-8 students (adjusted OR 4.7, 95% CI 1.3-16.6). Students who did not have latrines at their home were at higher risk to develop STHs infection comparing with those who had latrine at their home (adjusted OR 5.0, 95% CI 1.7-15.2). Similarly, the school children who did not wear shoes were more likely to be infected by STH parasite than those who did it (adjusted OR 6.3, 95% CI 1.9-20.7). The odds of being infected by STH parasites in children who did not trim their fingernails were 4.9 as compared to those who did it (adjusted OR 4.9, 95% CI 1.5-15.7). Conclusions: The prevalence of STHs among Endemata primary school children was low. Student grade level, latrine availability, shoes wear and nail status were significantly associated with STHs infection. Therefore, we recommend policy makers and stakeholders to follow the integration of deworming with water, hygiene and sanitation as well as the consistent health education of school children to control and prevent STH infections.

Antimicrobial susceptibility and serotypes of Neisseria meningitidis and Streptococcus pneumoniae in Sri Lanka: Experience from the National Reference Laboratory

@# Objective: To determine the antimicrobial susceptibility and serotypes of Neisseria (N.) meningitidis and Streptococcus (S.) pneumoniae in Sri Lankan patients. Methods: We retrospectively analyzed 11 blood culture specimens from suspected patients with invasive meningococcal disease and 26 S. pneumoniae clinical isolates. We tested 6 antimicrobials against N. meningitidis and 12 antimicrobials against S. pneumoniae. Meningococcal serogroup was determined by realtime PCR and Quellung serotyping was used for pneumococcal analysis. Results: N. meningitidis serogroup B was the most common in this study. Intermediate-susceptibility to penicillin was seen in 75.0% (6/8) of strains. Susceptibility to ciprofloxacin, levofloxacin and cotrimoxazole was 62.5% (5/8), 62.5% (5/8) and 87.5% (7/8), respectively. Excellent susceptibility was seen in cefotaxime and meropenem. In S. pneumoniae, the most common serotype was 19F in both invasive and non-invasive pneumococcal diseases. The majority of strains showed multidrug resistance. Penicillin non-susceptibility in non-meningeal strains were 13.6% and all meningeal strains were penicillin resistant. Erythromycin was highly resistant in both groups. Amoxicillin showed excellent susceptibility in non-invasive pneumococcal diseases strains. Linezolid, levofloxacin and vancomycin showed 100.0% susceptibility in all pneumococcal isolates. Conclusions: Implementation of vaccines should be considered, especially for children and high-risk populations. This may contribute to reducing pneumococcal and meningococcal invasive disease burden and help prevent emergence of antimicrobial resistant strains.