Search results for: latent tuberculosis infection

Authors: Alaa Badawi, Suzan Sayegh, Mohamed Sallam, Eman Sadoun, Mohamed Al-Thani, Muhammad W. Alam, Paul Arora

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Background: The dual burden of tuberculosis (TB) and diabetes mellitus (DM) has increased over the past decade with DM prevalence increasing in countries already afflicted with a high burden of TB. The coexistence of the two conditions presents a serious threat to global public health. Objective: The present study examines the global relationship between the prevalence of DM and the incidence of TB to evaluate their coexistence worldwide and their contribution to one another. Methods: This is an ecological longitudinal study covering the period between years 2000 to 2012. We utilized data from the WHO and World Bank sources and International Diabetes Federation to estimate prevalence of DM (%) and the incidence of TB (per 100,000). Measures of central tendency and dispersion as well as the harmonic mean and linear regression were used for different WHO regions. The association between DM prevalence and TB incidence was examined by quartile of DM prevalence. Results: The worldwide average (±S.D.) prevalence of DM within the study period was 6.6±3.8% whereas TB incidence was 135.0±190.5 per 100,000. DM prevalence was highest in the Eastern Mediterranean (8.3±4.1) and West Pacific (8.2±5.6) regions and lowest in the Africa (3.5±2.6). TB incidence was highest in Africa (313.1±275.9 per 100,000) and South-East Asia (216.7±124.9) and lowest in the European (46.5±68.6) and American (47.2±52.9) regions. Only countries with high DM prevalence (>7.6%) showed a significant positive association with TB incidence (r=0.17, p=0.013). Conclusion: A positive association between DM and TB may exist in some – but not all – world regions, a dual burden that necessitates identifying the nature of this coexistence to assist in developing public health approaches that curb their rising burden.

Keywords: diabetes mellitus, tuberculosis, disease burden, global association

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Authors: Akinsola Oluwatosin, Udofia Samuel, Odofin Mayowa

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The study is aimed at assessing the Geographic Information System (GIS)-based spatial analysis of Survival Pattern and Treatment Outcomes of Multi-Drug Resistant Tuberculosis (MDR-TB) cases for Lagos, Nigeria, with an objective to inform priority areas for public health planning and resource allocation. Multi-drug resistant tuberculosis (MDR-TB) develops due to problems such as irregular drug supply, poor drug quality, inappropriate prescription, and poor adherence to treatment. The shapefile(s) for this study were already georeferenced to Minna datum. The patient’s information was acquired on MS Excel and later converted to . CSV file for easy processing to ArcMap from various hospitals. To superimpose the patient’s information the spatial data, the addresses was geocoded to generate the longitude and latitude of the patients. The database was used for the SQL query to the various pattern of the treatment. To show the pattern of disease spread, spatial autocorrelation analysis was used. The result was displayed in a graphical format showing the areas of dispersing, random and clustered of patients in the study area. Hot and cold spot analysis was analyzed to show high-density areas. The distance between these patients and the closest health facility was examined using the buffer analysis. The result shows that 22% of the points were successfully matched, while 15% were tied. However, the result table shows that a greater percentage of it was unmatched; this is evident in the fact that most of the streets within the State are unnamed, and then again, most of the patients are likely to supply the wrong addresses. MDR-TB patients of all age groups are concentrated within Lagos-Mainland, Shomolu, Mushin, Surulere, Oshodi-Isolo, and Ifelodun LGAs. MDR-TB patients between the age group of 30-47 years had the highest number and were identified to be about 184 in number. The outcome of patients on ART treatment revealed that a high number of patients (300) were not ART treatment while a paltry 45 patients were on ART treatment. The result shows the Z-score of the distribution is greater than 1 (>2.58), which means that the distribution is highly clustered at a significance level of 0.01.

Keywords: tuberculosis, patients, treatment, GIS, MDR-TB

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Authors: Azeddine El-Hassouny, Chandrashekhar Meshram, Geraldin Nanfack

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In recent years, learning from data with noisy labels (Label Noise) has been a major concern in supervised learning. This problem has become even more worrying in Deep Learning, where the generalization capabilities have been questioned lately. Indeed, deep learning requires a large amount of data that is generally collected by search engines, which frequently return data with unreliable labels. In this paper, we investigate the Label Noise in Deep Learning using variational inference. Our contributions are : (1) exploiting Label Noise concept where the true labels are learnt using reparameterization variational inference, while observed labels are learnt discriminatively. (2) the noise transition matrix is learnt during the training without any particular process, neither heuristic nor preliminary phases. The theoretical results shows how true label distribution can be learned by variational inference in any discriminate neural network, and the effectiveness of our approach is proved in several target datasets, such as MNIST and CIFAR32.

Keywords: label noise, deep learning, discrete latent variable, variational inference, MNIST, CIFAR32

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Authors: Matthew John F. Sino Cruz, Sarah Jane M. Ferrer, Janice C. Francisco

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COVID-19 pandemic has affected more than 114 countries all over the world since it was considered a global health concern in 2020. Different sectors, including education, have shifted to remote/distant setups to follow the guidelines set to prevent the spread of the disease. One of the higher education institutes which shifted to remote setup is the Pangasinan State University (PSU). In order to continue providing quality instructions to the students, PSU designed Flexible Learning Model to still provide services to its stakeholders amidst the pandemic. The model covers the redesigning of delivering instructions in remote setup and the technology needed to support these adjustments. The primary goal of this study is to determine the insights of the PSU – Bayambang students towards the remote setup implemented during the pandemic and how they perceived the initiatives employed in relation to their experiences in flexible learning. In this study, the topic modelling approach was implemented using Latent Dirichlet Allocation. The dataset used in the study. The results show that the most common concern of the students includes time and resource management, poor internet connection issues, and difficulty coping with the flexible learning modality. Furthermore, the findings of the study can be used as one of the bases for the administration to review and improve the policies and initiatives implemented during the pandemic in relation to remote service delivery. In addition, further studies can be conducted to determine the overall sentiment of the other stakeholders in the policies implemented at the University.

Keywords: COVID-19, topic modelling, students’ sentiment, flexible learning, Latent Dirichlet allocation

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Authors: Estefania Ponce-Amaya, Ana Lidia Arellano-Ortiz, Cecilia Diaz-Hernandez, Jose Alberto Lopez-Diaz, Antonio De La Mora-Covarrubias, Claudia Lucia Vargas-Requena, Mauricio Salcedo-Vargas, Florinda Jimenez-Vega

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Cervical Cancer (CC) is the second leading cause of death among women worldwide and it had been associated with a persistent infection of human papillomavirus (HPV). The goal of the current study was to identify the prevalence of HPV infection in women with abnormal Pap smear who were attended at Dysplasia Clinic of Ciudad Juarez, Mexico. Methods: Cervical samples from 146 patients, who attended the Colposcopy Clinic at Sanitary Jurisdiction II of Cd Juarez, were collected for histopathology and molecular study. DNA was isolated for the HPV detection by Polymerase Chain Reaction (PCR) using MY09/011 and GP5/6 primers. The associated risk factors were assessed by a questionnaire. The statistical analysis was performed by ANOVA, using EpiINFO V7 software. Results: HPV infection was present in 142 patients (97.3 %). The prevalence of HPV infection was distributed in a 96% of all evaluated groups, low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HISIL) and CC. We found a statistical significance (α = <0.05) between gestation and number of births as risk factors. The median values showed an ascending tend according with the lesion progression. However, CC showed a statistically significant difference with respect to the pre-carcinogenic stages. Conclusions: In these Mexican patients exists a high prevalence of HPV infection, and for that reason, we are studying the most prevalent HPV genotypes in this population.

Keywords: cervical cancer, HPV, prevalence hpv, squamous intraepithelial lesion

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Authors: Sergio Paez Moncaleano, Alvaro Mauricio Montenegro

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This paper presents a novel statistical methodology for measuring and founding constructs in Latent Regression Analysis. This approach uses the qualities of Factor Analysis in binary data with interpretations on Item Response Theory (IRT). In addition, based on the fundamentals of submodel theory and with a convergence of many ideas of IRT, we propose an algorithm not just to solve the dimensionality problem (nowadays an open discussion) but a new research field that promises more fear and realistic qualifications for examiners and a revolution on IRT and educational research. In the end, the methodology is applied to a set of real data set presenting impressive results for the coherence, speed and precision. Acknowledgments: This research was financed by Colciencias through the project: 'Multidimensional Item Response Theory Models for Practical Application in Large Test Designed to Measure Multiple Constructs' and both authors belong to SICS Research Group from Universidad Nacional de Colombia.

Keywords: item response theory, dimensionality, submodel theory, factorial analysis

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Authors: Sihame Amakrane, Zineb Ouahdi, Mohammed Salah, Said Belaaouad

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\This research explores the efficacy of novel pyrimidine derivatives on bacterial strains such as Escherichia coli, Staphylococcus aureus, and Myccobacterium tuberculosis, utilizing bending energy calculations. Of the 25 compounds examined, 13 displayed potent activity against all the bacterial strains under study, exhibiting bending energy measurements between -7.4 and -10.7 kcal/mol. The -7.4 kcal/mol value corresponds to the bending energy of the SA12 and SA13 compounds with the 2xct protein (Staphylococcus aureus), whereas the -10.7 kcal/molis linked with the bending energy of SA6 and SA11 compounds with the 6GAV protein (Myccobacterium tuberculosis). Further research will involve a QSAR (Quantitative Structure-Activity Relationship) study aimed at constructing a reliable model to combat the aforementioned bacterial strains and a molecular dynamics study to evaluate the stability of ligand-protein complexes.

Keywords: docking, QSAR, bending energy, e. coli

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Authors: Jiranun Sreecharit, Anongnat Boonrut, Kunvadee Munvaradee, Phechnoy Singchungchai

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Hatyai Hospital as center of hospital with a capacity of 670 beds. Medicine intensive care units (MICU240) provide care for critically ill patients who are at high risk need to be monitored closely. Intravenous catheter is vital to help assess the level of water in the body fluids and medications. Potential complications such as infection. We need to have guidelines for the care of patients who received intravenous catheter used to achieve good results. The operations research in this study was intended 1) To study the effects of practice for nurses in caring for patients with central venous catheter to infection rate and 2) To assess the satisfaction of nurses and patient care practices in central venous catheterization patients in the MICU 240. The sample of the patient's central venous catheter crisis that everyone who admitted in MICU 240 during the period from October 2013 to May 2014. Samples prior to practice and 148 samples with 249 case of practice. A systematic review of the research NSWHealth Statewide Guideline for Intensive Care. Data were analyzed by statistics, percentages and frequency NON-PARAMETRICS with Mann-Whitney U. The finding revealed that: 1. Results of the practice patient care central venous catheter infection rates were found to be reduced from 35.14 percent to 25.3 percent. 2. The results of the evaluation of nurses and patients in the patient care practices central venous catheter found to be satisfied and happy to work 85 percent.

Keywords: clinical practice guidelines, central venous catheter, infection satisfaction

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Authors: Marco Sewald

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Comparing present to past the numbers of Americans expatriating U. S. citizenship have risen. Even though these numbers are small compared to the immigrants, U. S. citizens expatriations have historically been much lower, making the uptick worrisome. In addition, the published lists and numbers from the U.S. government seems incomplete, with many not counted. Different branches of the U. S. government report different numbers and no one seems to know exactly how big the real number is, even though the IRS and the FBI both track and/or publish numbers of Americans who renounce. Since there is no single explanation, anecdotal evidence suggests this uptick is caused by global tax law and increased compliance burdens imposed by the U.S. lawmakers on U.S. citizens abroad. Within a research project the question arose about the reasons why a constant growing number of U.S. citizens are expatriating – the answers are believed helping to explain the underlying governmental policy rational, leading to such activities. While it is impossible to locate former U.S. citizens to conduct a survey on the reasons and the U.S. government is not commenting on the reasons given within the process of expatriation, the chosen methodology is Structural Equation Modeling (SEM), in the first step by re-using current surveys conducted by different researchers within the population of U. S. citizens residing abroad during the last years. Surveys questioning the personal situation in the context of tax, compliance, citizenship and likelihood to repatriate to the U. S. In general SEM allows: (1) Representing, estimating and validating a theoretical model with linear (unidirectional or not) relationships. (2) Modeling causal relationships between multiple predictors (exogenous) and multiple dependent variables (endogenous). (3) Including unobservable latent variables. (4) Modeling measurement error: the degree to which observable variables describe latent variables. Moreover SEM seems very appealing since the results can be represented either by matrix equations or graphically. Results: the observed variables (items) of the construct are caused by various latent variables. The given surveys delivered a high correlation and it is therefore impossible to identify the distinct effect of each indicator on the latent variable – which was one desired result. Since every SEM comprises two parts: (1) measurement model (outer model) and (2) structural model (inner model), it seems necessary to extend the given data by conducting additional research and surveys to validate the outer model to gain the desired results.

Keywords: expatriation of U. S. citizens, SEM, structural equation modeling, validating

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Authors: Parveen Kundu, Zile Singh, Kunika Kundu, Swaran Kaur

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Context: Tuberculous osteomyelitis is a relatively uncommon condition that can present with various clinical and radiological features, often mimicking bone tumors or tumor-like lesions. In endemic countries like India, tuberculosis should be considered as a potential differential diagnosis for lytic bone lesions. This study aimed to highlight the different presentations of tuberculosis that can mimic tumors or tumor-like lesions in bone and emphasize the successful outcome of antitubercular therapy (ATT) in treating these cases. Research Aim: The main objective of this research was to explore the varied presentations of tuberculosis that mimic bone tumors or tumor-like lesions both clinically and radiologically, focusing on different bones. The study aimed to raise awareness among clinicians about this possibility and highlight the importance of histopathological confirmation before initiating treatment for lytic bone lesions. Methodology: This study utilized a retrospective review of 22 patients with suspected lytic bone lesions, who were subsequently diagnosed with tuberculous osteomyelitis through histopathological examination. The cases were collected over a period of ten years. Eleven cases required curettage for extensive lesions with sequestrations, while all 22 patients received 12 months of antitubercular therapy. Findings: The study included 14 male and 8 female patients, ranging in age from 3 to 61 years, with an average age of 22.05. The clinical and radiological presentations varied, with examples including bone cysts in the metaphyseal area of long bones, lesions resembling chondroblastomas, giant cell tumors, and osteoid osteoma, as well as multifocal lytic lesions resembling metastasis or multiple myeloma. One patient had lesions in both the clavicle and hand. Lesions mimicking chondromas were also observed in the phalanges of the hand and foot metatarsal. All patients showed resolution of the lesions and no residual disability following ATT. Theoretical Importance: This study highlights the importance of considering tuberculosis as a potential differential diagnosis for lytic bone lesions, particularly in endemic regions. It emphasizes the need for histopathological confirmation to accurately diagnose tuberculous osteomyelitis, as this is considered the gold standard. Data Collection and Analysis Procedures: Data for this study were collected retrospectively from medical records and radiological images of the 22 patients. The cases were analyzed based on clinical presentation, radiological findings, and histopathological confirmation. The outcomes of antitubercular therapy were also assessed. The data were summarized and presented descriptively. Question Addressed: This study aimed to address the question of how tuberculosis can mimic different bone tumors and tumor-like lesions clinically and radiologically. It also aimed to assess the successful outcome of antitubercular therapy in treating these cases. Conclusion: Tuberculous osteomyelitis can present with varied clinical and radiological features, often mimicking bone tumors or tumor-like lesions. Clinicians should consider tuberculosis as a potential diagnosis for lytic bone lesions, especially in endemic areas. Histopathological confirmation is essential for accurate diagnosis. Antitubercular therapy is an effective treatment for tuberculous osteomyelitis, leading to the resolution of the lesions with no residual disability.

Keywords: tuberculosis, tumor, curettage, bone

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Authors: Tadesse Menjetta, Daniel Dana, Serkadis Debalke

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Schistosomiasis/Bilharziasis is one of the neglected tropical parasitic diseases caused by different species of genus Schistosoma. Among the species, S. mansoni (causative agents of intestinal schistosomiasis) is one of the causes of severe intestinal parasitic infections with high public and medical importance in Ethiopia. There is a scarcity of information about the status of S. mansoni infection among the fisherman in our study area and in the country at large. Therefore, this study was designed to determine the prevalence and risk factors of S.mansoni infection among fishermen at Lake Hawassa, southern Ethiopia. A cross-sectional study was conducted among the fishermen from April to June 2013 in Hawassa, Southern Ethiopia. A total of 243 fishermen were included by systematic sampling from the lists of the fishermen members in the registration book of fishermen associations in the Hawassa Town. Data on socio-demographic features and risk factors were collected by using semi-structured questionnaires. Stool samples were collected and processed using Kato-Katz thick smear techniques and examined between 30- 40 minute for hookworm and after 24 hours for S. mansoni and other soil-transmitted helminths (STHs). The overall prevalence of S.mansoni among the fishermen was 29.21% (71/243), and the mean intensity of infection was 158.88 egg per gram (EPG). The prevalence of intestinal helminths including S. mansoni was 69.54% (169/243). Moreover, the prevalence of soil-transmitted helminths (STHs) was 40.74% (99/243), 35.80% (87/243) and 5.76% (14/243) for A. lumbricoides, T. trichiura and hookworm species, respectively. Almost similar prevalence of S.mansoni, 31.82%, 31.75%, 31.94% were recorded in age groups of 15-19, 20-24 and 25-29 years, respectively. Fishermen who are swimming always were 2.92 times [95% CI: 1.554, 5.502] more likely to acquire S. mansoni infection than other water contacting habit of the study participants. The results of the current investigation indicated the moderate endemicity of S. mansoni among the fishermen at Lake Hawassa, southern Ethiopia. Fishermen could be the potential risk group for S. mansoni infection and might be responsible for the transmission of S. mansoni to other segments of the communities. Since the high prevalence of STH was recorded among the fishermen, integrated prevention and control strategies from different sectors might be important to tackle the problem.

Keywords: S. mansoni, soil transmitted helminths, fishermen, Lake Hawassa, Ethiopia

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Authors: Shahla Rostamirad

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Purpose: Giardiasis is a widespread infection in humans caused by Giardia lamblia. The prevalence of this parasite among children in Isfahan of Iran is unknown. This study intended to estimate Giardia lamblia infection prevalence and identify possible associated risk factors in a healthy pediatric population living in the Isfahan, a metropolitan city of Iran. Methods: Between September 2010 and March 2012, 1448 stool sample from children with clinical manifestation that refer to clinical lab in Isfahan city for stool examination were collected and analyzed. About 1218 samples were positive for parasitic disease. All of samples were examined and diagnosed by direct examination and formalin-ether concentration of stools. Results: A total of 1218 positive cases were analyzed in this study. The findings showed that 92.5% of patients were infected by protozoa and 7.5 percent with helminth infection. The highest and lowest rate of infection belongs to Giardia lamblia and Entamoeba histolytica with 75% and 1.1%, respectively. Other infection cases were included of Blastocystys hominis 9.9%, E. coli 6.5%, H. nana 1.3%, Enterobious vermicolaris 4% and Ascaris lumbricoides 2.2% percent. The population studied revealed a gender distribution of 53.2% male and 46.8% female. Age distribution was 57.3% between 0-5 years and 42.7% between 6-15 years.The prevalence was higher among children aged 0-5 years (57.8%), than among older children (42.2%). Conclusion: The prevalence of protozoan parasite, especially Giardiasis, in children residing in the region of Isfahan is high. Several risk factors were associated with this prevalence and highlight the importance of parents' education and sanitation conditions in the children's well being. The association between Giardia lamblia and H. pylori seems an important issue deserving further investigation in order to promote prevention or treatment strategies. Other risk factor include presence of Helicobacter pylori infection, living in houses with own drainage system and reported household, pet contact, especially with cat and dog.

Keywords: Giardia duodenalis, prevalence, risk factors, children, Isfahan, Iran

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Authors: Mohammad Saifuddin, Shahjada Selim

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Patients with diabetes mellitus (DM) are prone to develop infection, especially urinary tract infection (UTI) in comparison with non-diabetics. Due to the emergence of multidrug resistant (MDR) uropathogenic strains, the choice of antimicrobial agent is sometimes difficult. This study is designed to reveal the distribution of uropathogens in Diabetic patients and corresponding sensitivity patterns and to correlate the microbiological results with various clinical parameters. A nine-month retrospective review of 100 urine culture reports of Diabetic patients from January 2015 to September 2015 from semiurbanmultispeciality hospital of Feni, Bangladesh were analyzed. Only Diabetic patients were included in this study who were clinically diagnosed as UTI patients with a corresponding urine culture showing a bacterial count of ˃105cfu/ml.Out of 100 patients with UTI, 39 (39%) were male, and 61 (61%) were female. Organisms grown in urine culture were Escherichia coli (64) followed by Klebsiella (11), Proteus (7), Staph Aureus (4), Pseudomonas (4), Acinetobacter (3), Sreptococcus(3), Enterococcus (2 ) and one each of Enterobacter and Fungi. Overall sensitivity pattern in decreasing order of various commonly used antibiotics was Meropenem (89%), Nitrofurantoin (86%), Amikacin (81%), Ceftriaxone (68%), Cefuroxime (61%), Cefixime (39%), Quinolones (28%), Amoxicillin (16%). The significance of the study lies in the determination of common pathogens in diabetic patients with UTI and the resistance pattern of antibiotics so that physicians and pharmacists get the proper information rationalizing the rational use of antibiotics.

Keywords: Bangladesh, Diabetes Mellitus, E. coli, urinary tract infection

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Authors: Gail Louw, Helena Boshoff, Taeksun Song, Clifton Barry

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Drug resistance in Mycobacterium tuberculosis is primarily attributed to mutations in target genes. These mutations incur a fitness cost and result in bacterial generations that are less fit, which subsequently acquire compensatory mutations to restore fitness. We hypothesize that mutations in specific drug target genes influence bacterial metabolism and cellular function, which affects its ability to develop subsequent resistance to additional agents. We aim to determine whether the sequential acquisition of drug resistance and specific mutations in a well-defined clinical M. tuberculosis strain promotes or limits the development of additional resistance. In vitro mutants resistant to pretomanid, linezolid, moxifloxacin, rifampicin and kanamycin were generated from a pan-susceptible clinical strain from the Beijing lineage. The resistant phenotypes to the anti-TB agents were confirmed by the broth microdilution assay and genetic mutations were identified by targeted gene sequencing. Growth of mono-resistant mutants was done in enriched medium for 14 days to assess in vitro fitness. Double resistant mutants were generated against anti-TB drug combinations at concentrations 5x and 10x the minimum inhibitory concentration. Subsequently, mutation frequencies for these anti-TB drugs in the different mono-resistant backgrounds were determined. The initial level of resistance and the mutation frequencies observed for the mono-resistant mutants were comparable to those previously reported. Targeted gene sequencing revealed the presence of known and clinically relevant mutations in the mutants resistant to linezolid, rifampicin, kanamycin and moxifloxacin. Significant growth defects were observed for mutants grown under in vitro conditions compared to the sensitive progenitor. Mutation frequencies determination in the mono-resistant mutants revealed a significant increase in mutation frequency against rifampicin and kanamycin, but a significant decrease in mutation frequency against linezolid and sutezolid. This suggests that these mono-resistant mutants are more prone to develop resistance to rifampicin and kanamycin, but less prone to develop resistance against linezolid and sutezolid. Even though kanamycin and linezolid both inhibit protein synthesis, these compounds target different subunits of the ribosome, thereby leading to different outcomes in terms of fitness in the mutants with impaired cellular function. These observations showed that oxazolidinone treatment is instrumental in limiting the development of multi-drug resistance in M. tuberculosis in vitro.

Keywords: oxazolidinones, mutations, resistance, tuberculosis

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Authors: Muhammad S. Sajid, Asim Shamim, Muhammad Nisar Khan, Ashfaq A. Chatta, Muhammad Saqib

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Goats (Capra hircus) are a valued asset for resource poor farmers globally. But the parasitic infection especially Haemonchus contortus (Trichostrongylid), impact the health and production of goats globally. The present study intended to evaluate resilient and resistance to Haemonchus contortus in indigenous goat breeds (Teddy and Beetal) of Punjab, Pakistan. Out of 60, 30 goats of each breed were divided into 6 groups and each group contain five goats. Two group of each breed received challenged infection with 12000 and 18000 L3 (third stage) larvae of Haemonchus contortus under two infection protocol that is early and trickle and remaining two group of each breed was kept as control. Resilient and resistance of each breed was then measured on the basis of their phenotypic markers like: faecal egg counts, packed cell volume, FAMACHA score system, body weight, total protein, albumin and worm count on 2nd, 4th, 6th, and 8th week of post infection. Variation in response of each goat breeds to Haemonchus contortus was observed. Teddy breed showed significant (P < 0.05)resistance as compared to Beetal. It is probably first attempt to report an evaluation of goat breed response towards Haemonchus contortus in Pakistan. It was concluded that Teddy goats have a greater genetic tendency to resist against to the Haemonchus contortus infection and this breed could be kept and bred from the economic point of view. Evaluation of genetic markers are like: gene, protein expression, Immunoglobulin, Histamines and interleukins determination are recommended for future studies which can be helpful to be fined resistant breed of goats.

Keywords: goat, beetal, teddy, haemonchus contortus, resistance, resilience, phenotypic markers

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Authors: Nilima Barman, M. Atiqul Haque, Debabrata Ghosh

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Background: Zinc, one of the vital micronutrients, has an incredible role in the immune system. Hypozincemia affects host defense by reducing the number of circulating T cells and phagocytosis activity of other cells which ultimately impair cell-mediated immunity 1, 2. The immune system is detrimentally suppressed in multidrug-resistant tuberculosis (MDR-TB) 3, 4, a major threat of TB control worldwide5. As zinc deficiency causes immune suppression, we assume that it might have a role in the development of MDR-TB. Objectives: To estimate the serum zinc level in newly diagnosed multidrug resistant tuberculosis (MDR-TB) in comparison with that of newly diagnosed pulmonary TB (NdPTB) and healthy individuals. Materials and Methods: This study was carried out in the department of Public Health and Informatics, Bangabandhu Sheikh Mujib Medical University, Dhaka in collaboration with National Institute of Diseases of the Chest Hospital (NIDCH), Bangladesh from March’ 2012 to February 2013. A total of 337 respondents, of them 107 were MDR TB patients enrolled from NIDCH, 69 were NdPTB and 161 were healthy adults. All NdPTB patients and healthy adults were randomly selected from Sirajdikhan subdistrict of Munshiganj District. It is a rural community 22 kilometer south from capital city Dhaka. Serum zinc level was estimated by atomic absorption spectrophotometry method from early morning fasting blood sample. The evaluation of serum zinc level was done according to normal range from 70 to120 µgm/dL6. Results: Males were predominant in study groups (p>0.05). Mean (sd) serum zinc levels in MDR-TB, NdPTB and healthy adult group were 65.14 (12.52), 75.22(15.89), and 87.98 (21.80) μgm/dL respectively and differences were statistically significant (F=52.08, P value<0.001). After multiple comparison test (Bonferroni test) significantly lower level of serum zinc was found in MDRTB group than NdPTB and healthy adults (p<.001). Point biserial correlation showed a negative association of having MDR TB and serum zinc level (r= -.578; p value <0.001). Conclusion: The significant low level of serum zinc in MDR-TB patients suggested impaired immune status. We recommended for further exploration of low level of serum zinc as risk factor of MDR TB.

Keywords: Bangladesh, immune status, multidrug-resistant tuberculosis, serum zinc

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Authors: B. Kenny

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The complications associated with transfusions are well documented, with the serious hazards of transfusion (SHOT) reporting system continuing to report deaths and serious morbidity due to the transfusion of allogenic blood. Many different sources including the TRICC trial, NHMRC and Cochrane recommending similar transfusion triggers/guidelines. Recent studies found the rate of infection (deep infection, wound infection, chest infection, urinary tract infection, and others) were purely a dose response relationship, increasing the Relative Risk by 3.44. It was also noted that each transfused patient stayed in hospital for one additional day. We hypothesise that providing an approved/standardised, guideline with a graphical summary of decision pathways for anaemic patients will reduce unnecessary transfusions. We retrospectively assessed patients undergoing primary knee or hip arthroplasties over a 4 year period, 1459 patients. Of these, 339 (23.24%) patients received allogenic blood transfusions and 858 units of blood were transfused, 9.14% of patients transfused had haemoglobin levels above 100 g/L, 7.67% of patients were transfused without knowing the haemoglobin level, 24 hours prior to transfusion initiation and 4.5% had possible transfusion reactions. Overall, 17% of allogenic transfusions topatients admitted to the Orthopaedic department within a 4 year period were outside NHMRC and Cochrane guidelines/recommendations. If our transfusion frequency is compared with that of other authors/hospitals, transfusion rates are consistently being high. We subsequently implemented a simple guideline for transfusion initiation. This guideline was then assessed. We found the transfusion rate post transfusion implementation to be significantly lower, without increase in patient morbidity or mortalitiy, p <0.001). Transfusion rates and patient outcome can be optimized by a simple graphical aid for decision making.

Keywords: transfusion, morbidity, mortality, neck of femur, fracture, arthroplasty, rehabilitation

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Authors: Sajewicz-Krukowska Joanna, Domańska-Blicharz Katarzyna, Tarasiuk Karolina, Marzec-Kotarska Barbara

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Astroviral infections pose a significant problem in the poultry industry, leading to multiple adverse effects such as decreased egg production, breeding disorders, poor weight gain, and even increased mortality. Commonly observed chicken astrovirus (CAstV) was recently reported to be responsible for "white chicks syndrome" associated with increased embryo/chick mortality. The CAstV-mediated pathogenesis in chicken occurs due to complex interactions between the infectious pathogen and the immune system. Many aspects of CAstV-chicken interactions remain unclear, and there is no information available regarding gene expression changes in the chicken's spleen in response to CAstV infection. We aimed to investigate the molecular background triggered by CAstV infection. Ten 21-day-old SPF White Leghorn chickens were divided into two groups of 5 birds each. One group was inoculated with CAstV, and the other was used as the negative control. On 4th dpi, spleen samples were collected and immediately frozen at -70°C for RNA isolation. We analysed transcriptional profiles of the chickens' spleens at the 4th day following infection using RNA-seq to establish differentially expressed genes (DEGs). The RNA-seq findings were verified by quantitative real-time PCR (qRT-PCR). A total of 31959 transcripts were identified in response to CAstV infection. Eventually 45 DEGs (p-value<0.05; Log2Foldchange>1)were recognized in the spleen after CAstV infection (26 upregulated DEGs and 19 downregulated DEGs). qRT-PCR performed on 4 genes (IFIT5, OASL, RASD1, DDX60) confirmed RNAseq results. Top differentially expressed genes belonged to novel putative IFN-induced CAstV restriction factors. Most of the DEGs were associated with RIG-I–like signalling pathway or, more generally, with an innate antiviral response(upregulated: BLEC3, CMPK2, IFIT5, OASL, DDX60, IFI6, and downregulated: SPIK5, SELENOP, HSPA2, TMEM158, RASD1, YWHAB). The study provided a global analysis of host transcriptional changes that occur during CAstV infection in vivo and proved the cell cycle in the spleen and immune signalling in chickens were predominantly affected upon CAstV infection.

Keywords: chicken astrovirus, CastV, RNA-seq, transcriptome, spleen

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Authors: Wen-Yu Lin, Yi-Ching Chung, Jhao-Ren Lin, Tzyy-Rong Jinn

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It is well known that enterovirus 71(EV71) causes recurring outbreaks of hand, foot and mouth disease and encephalitis leading to complications or death in young children. And, several enterovirus 71 (EV71) of hand foot and mouth disease (HFMD) with high mortalities occurred in Asia country, such as Hong Kung (1985), Malaysia (1997), Taiwan (1998) and China (2008) that EV71 results in severe neurological complications and sudden death in infants and young children. However, there are still no effective drugs and vaccines to reduce and inhibit EV71 infection. Therefore, the development of specific and effective antiviral strategies against EV71 has become an urgent issue for the protection of children from the hazards of the HFMD. As reported, amantadine is effective in prophylaxis and treatment of the EV71 infections. Thus, the aim of this study was to further evaluate the synergistic antiviral activity of amantadine coupled with magnesium lithospermate B (MLB) against enterovirus 71 infection. In a preliminary test, it is shown that the infected RD cells were treated with amantadine after virus absorption, at concentrations of 3 and 5µM of amantadine suppressed EV71-induced CPE to 13% and 23%, respectively at MOI of 3. Alternatively, at concentrations of 5µg/ml of MLB combined with 3 and 5 µM of amantadine apparently suppressed EV71-induced CPE to 45% and 63%, respectively at MOI of 3. Thus, amantadine coupled with MLB may have the potential for further study to development as the chemopreventive reagents against EV71 infection.

Keywords: amantadine, Enterovirus 71, magnesium lithospermate B, RD cells, synergistic effects

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Authors: Houda Haddad, Nolwen Jouvenet, Maxime Chazal, Frédéric Tangy, Amira Zairi

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Zika virus represents the primary cause of infection during pregnancy and can lead to various neurological disorders, such as microcephaly and Guillain-Barré syndrome, affecting both children and adults. This infection is also associated with urological and nephrological problems. So far, evidence of mosquito-borne Zika virus infection has been reported in a total of 89 countries and territories. However, surveillance efforts primarily concentrate on outbreaks that this virus can cause, yet the measures implemented are typically limited. Currently, there are no specific treatments or vaccines designed for the prevention or treatment of Zika virus infection or its associated disease. The development of effective therapeutic agents presents an urgent need. Importantly, an alternative for advancing the discovery of molecules could be dermaseptins, a family of antimicrobial peptides known for their potential antiviral properties. In this study, we carried out the synthesis of dermaseptins and their analogs and subsequently assessed the bioactivity tests against Zika virus (ZIKV PF13) of dermaseptins B2 and S4 and their derivatives. The cytotoxicity of these peptides was investigated on the HMC3 cell line and HeLa cells by CellTiter-Glo® Luminescent Cell Viability Assay. Thereafter, we evaluated the antiviral activity caused by the action of our dermaseptins on the viral envelope using the Fluorescence Activated Cell Sorting (FACS). The cytotoxicity of our molecules was concentration-dependent at microgram concentrations except for dermaseptin B2 and its derivative, which present no toxicity against HeLa and HMC3 cell lines. It was observed that all tested analogs from the S4 family exhibited antiviral activity with low concentrations ranging from 3 to 12.5 μg/mL, unlike the native B2 and its derivative, which increased the infectivity. Pre-incubating of dermaseptins with ZIKV PF13 before infection revealed that these derivatives inhibit the initial stages of virus infection. In summary, these results suggest that dermaseptins could serve as lead structures for the development of potent antiviral agents against Zika virus infections.

Keywords: dermaseptin B2, dermaseptin S4, analogs, zika virus, neurological infections, antiviral activity

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Authors: Selamawit Hirpa, Girmay Medhin, Belaineh Girma, Muluken Melese, Alemayehu Mekonen, Pedro Suarez, Gobena Ameni

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Worldwide, there were 650,000 multi-drug resistant tuberculosis (MDR-TB) cases in 2010. Ethiopia is 15th among the 27 MDR-TB high-burden countries. A case control study was conducted at St. Peter Hospital and five health centers in Addis Ababa. Cases were MDR-TB patients who were in treatment at St. Peter Hospital during the study period. Controls were patients who were on first-line anti-TB treatment and were registered as cured or having completed treatment in the period 9 April 2009– 28 February 2010, in five health centers. A structured interview questionnaire was used to assess factors that could potentially be associated with the occurrence of MDR-TB. Factors that were significantly associated with MDR-TB: drug side effects during first-line treatment (adjusted odds ratio (AOR): 4.5, 95% CI; 1.9 - 10.5); treatment not directly observed by a health worker (AOR = 11.7, 95% CI; 4–34.3); and retreatment with the Category II regimen (P = 0.000).

Keywords: adherence to TB treatment, MDR-TB, TB treatment, TB treatment regimens

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Authors: Shraddha Acharya, Sharad Kumar Sharma, Ratna Bhattarai, Bhagwan Maharjan, Deepak Dahal, Serpahine Kaminsa

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Background: Drug-resistant (DR) tuberculosis (TB) continues to be a threat in Nepal, with an estimated 2800 new cases every year. The treatment of DR-TB with second line TB drugs is complex and takes longer time with comparatively lower treatment success rate than drug-susceptible TB. Delay in treatment initiation for DR-TB patients might further result in unfavorable treatment outcomes and increased transmission. This study thus aims to determine median time taken to initiate second-line treatment among Rifampicin Resistant (RR) diagnosed TB patients and to assess the proportion of treatment delays among various type of DR-TB cases. Method: A retrospective cohort study was done using national routine electronic data (DRTB and TB Laboratory Patient Tracking System-DHIS2) on drug resistant tuberculosis patients between January 2020 and December 2022. The time taken for treatment initiation was computed as– days from first diagnosis as RR TB through Xpert MTB/Rif test to enrollment on second-line treatment. The treatment delay (>7 days after diagnosis) was calculated. Results: Among total RR TB cases (N=954) diagnosed via Xpert nationwide, 61.4% were enrolled under shorter-treatment regimen (STR), 33.0% under longer treatment regimen (LTR), 5.1% for Pre-extensively drug resistant TB (Pre-XDR) and 0.4% for Extensively drug resistant TB (XDR) treatment. Among these cases, it was found that the median time from diagnosis to treatment initiation was 6 days (IQR:2-15.8). The median time was 5 days (IQR:2.0-13.3) among STR, 6 days (IQR:3.0-15.0) among LTR, 30 days (IQR:5.5-66.8) among Pre-XDR and 4 days (IQR:2.5-9.0) among XDR TB cases. The overall treatment delay (>7 days after diagnosis) was observed in 42.4% of the patients, among which, cases enrolled under Pre-XDR contributed substantially to treatment delay (72.0%), followed by LTR (43.6%), STR (39.1%) and XDR (33.3%). Conclusion: Timely diagnosis and prompt treatment initiation remain fundamental focus of the National TB program. The findings of the study, however suggest gaps in timeliness of treatment initiation for the drug-resistant TB patients, which could bring adverse treatment outcomes. Moreover, there is an alarming delay in second line treatment initiation for the Pre-XDR TB patients. Therefore, this study generates evidence to identify existing gaps in treatment initiation and highlights need for formulating specific policies and intervention in creating effective linkage between the RR TB diagnosis and enrollment on second line TB treatment with intensified efforts from health providers for follow-ups and expansion of more decentralized, adequate, and accessible diagnostic and treatment services for DR-TB, especially Pre-XDR TB cases, due to the observed long treatment delays.

Keywords: drug-resistant, tuberculosis, treatment initiation, Nepal, treatment delay

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Authors: Solomon Sisay, Belete Mengistu, Woldargay Erku, Desalegne Woldeyohannes

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Background: Tuberculosis is still the leading cause of illness in the world which accounted for 2.5% of the global burden of disease, and 25% of all avoidable deaths in developing countries. Objectives: The aim of study was to assess impact of DOTS strategy on tuberculosis case finding and treatment outcome in Gambella Regional State, Ethiopia from 2003 up to 2012 and from 2002 up to 2011, respectively. Methods: Health facility-based retrospective study was conducted. Data were collected and reported in quarterly basis using WHO reporting format for TB case finding and treatment outcome from all DOTS implementing health facilities in all zones of the region to Federal Ministry of Health. Results: A total of 10024 all form of TB cases had been registered between the periods from 2003 up to 2012. Of them, 4100 (40.9%) were smear-positive pulmonary TB, 3164 (31.6%) were smear-negative pulmonary TB and 2760 (27.5%) had extra-pulmonary TB. Case detection rate of smear-positive pulmonary TB had increased from 31.7% to 46.5% from the total TB cases and treatment success rate increased from 13% to 92% with average mean value of being 40.9% (SD= 0.1) and 55.7% (SD=0.28), respectively for the specified year periods. Moreover, the average values of treatment defaulter and treatment failure rates were 4.2% and 0.3%, respectively. Conclusion: It is possible to achieve the recommended WHO target which is 70% of CDR for smear-positive pulmonary TB, and 85% of TSR as it was already been fulfilled the targets for treatments more than 85% from 2009 up to 2011 in the region. However, it requires strong efforts to enhance case detection rate of 40.9% for smear-positive pulmonary TB through implementing alternative case finding strategies.

Keywords: Gambella Region, case detection rate, directly observed treatment short-course, treatment success rate, tuberculosis

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Authors: Chanya Jetsukontorn

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Dengue hemorrhagic fever is the most important Mosquito-borne disease and the major public health problem in Thailand. The most important vector is Aedes aegypti. Environmental factors such as temperature, relative humidity, and biting rate affect dengue virus infection. The most effective measure for prevention is controlling of vector mosquitoes. In addition, surveillance of field-caught mosquitoes is imperative for determining the natural vector and can provide an early warning sign at risk of transmission in an area. In this study, Aedes aegypti mosquitoes were collected in Amphur Muang, Phetchabun Province, Thailand. The mosquitoes were collected in the rainy season and the dry season both indoor and outdoor. During mosquito’s collection, the data of environmental factors such as temperature, humidity and breeding sites were observed and recorded. After identified to species, mosquitoes were pooled according to genus/species, and sampling location. Pools consisted of a maximum of 10 Aedes mosquitoes. 70 pools of 675 Aedes aegypti were screened with RT-PCR for flaviviruses. To confirm individual infection for determining True infection rate, individual mosquitoes which gave positive results of flavivirus detection were tested for dengue virus by RT-PCR. The infection rate was 5.93% (4 positive individuals from 675 mosquitoes). The probability to detect dengue virus in mosquitoes at the neighbour’s houses was 1.25 times, especially where distances between neighboring houses and patient’s houses were less than 50 meters. The relative humidity in dengue-infected villages with dengue-infected mosquitoes was significantly higher than villages that free from dengue-infected mosquitoes. Indoor biting rate of Aedes aegypti was 14.87 times higher than outdoor, and biting times of 09.00-10.00, 10.00-11.00, 11.00-12.00 yielded 1.77, 1.46, 0.68mosquitoes/man-hour, respectively. These findings confirm environmental factors were related to Dengue infection in Thailand. Data obtained from this study will be useful for the prevention and control of the diseases.

Keywords: Aedes aegypti, Dengue virus, environmental factors, one health, PCR

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Authors: Hue Dinh, Binh Nguyen, Vivian Mendez, Phillip W. Taylor, Fleur Ponton

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Better understanding of how parental diet affects offspring traits is an important ecological and evolutionary question. In this study, we explored how maternal diet influences offspring physiology and resistance to infection using Bactrocera tryoni (Q-fly) as a system model. Female Q-flies were fed one of six single diets varying in their yeast-to-sugar ratio yielding six protein-to-carbohydrate ratios. As controls, we used females that were given a choice between yeast and sugar. Males were reared on a choice diet and allowed to mate with females 14 days post-emergence. Results showed that while maternal diet does not influence offspring developmental time, it has a strong effect on larval body weight. Mother fed either high-protein or high-sugar diet produced larger progeny. By challenging offspring with the bacterium Serratia marcescens, we found that female offspring from mothers fed high-sugar diet survived better the infection compared to those from mothers fed low-sugar diet. In contrast, male offspring produced by mother fed high-protein diet showed better resistance to the infection compared to those produced by mother fed low-protein diet. These results suggested sex-dependent transgenerational effects of maternal nutrition on offspring physiology and immunity.

Keywords: bacterial infection, Bactrocera tryoni, maternal diet, offspring, Serretia marcescens

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Authors: Prasanta Saini, Junaid Jibran Jawed, Subrata Majumdar

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Infections caused by soil-transmitted helminths (STH) are the major problem in all the nations of the world. The major focus of STH research is to study the prevalence of three major helminths, such as Ascaris, Trituris and hookworm. Here we are reporting the prevalence and intensity of the STH in the school children of the state of Uttar Pradesh, India. The aim of the study is to assess the prevalence and risk factors of STH infection among the school children, aged between 5-10 years in 27 districts randomly selected districts with covering nine agro-climatic zones of Uttar Pradesh, India. For this cross-sectional survey, we have selected the populations of government primary school going children in Uttar Pradesh. The sampling was performed in the nine different agro-climatic zones. Every individual of the study populations filled their daily information in the questioner's form and then the sample was collected and processed by kato-katz methods by following the guidelines of WHO. In this method, the sampling was performed in total of 6421 populations. A total of 6,421 children from 130 schools were surveyed. Infection with any soil-transmitted helminths was detected among 4,578 children with an overall prevalence of 75.6% (95% CI: 65.3-83.6). Among the 6421 population, the prevalence of Ascaris is 69.6% (95% CL 57.97-79.11), hookworm is 22.7% (95%CL 19.3-26.3) and Trichuris sp is 4.6% (95% CL 0.8-21.6), so the predicted prevalence map indicates that the STH infection was hyperendemic in this state. The findings of our survey in 130 schools covering 9 agro-climatic with one or more soil transmitted helminths. Majority of STH infections were of light intensity. STH infection was hyper-endemic in entire state, except three zones in western Uttar Pradesh. High prevalence ( > 75%) in all age groups also indicate little impact of existing deworming initiatives, including those among pre-school aged children. WHO recommends annual treatment in areas where STH prevalence is between 20% and 50%, and, a bi-annual treatment in areas with prevalence rates of over 50%. In view of high prevalence of STH infection in Uttar Pradesh, it is strongly recommended to initiate a deworming programme for school children in the state. Although our survey was among primary school children, high prevalence among children aged 4-6 years also indicates the need to strengthen the existing deworming programs for pre-school children. Extending the benefits of deworming to pre-school children through deworming in Anganwadi schools would further reduce to decrease the load of infection in community. As a long-term solution for control STH infection, it is also necessary to improve the sanitation levels in the area, as majority of the houses did not have latrines and most of the children were defecating in open fields, a factor that was found to be significantly associated with STH infection.

Keywords: prevalence, school going children, soil transmitted helminthes, Uttar Pradesh-India

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Authors: Bandhan Dey, Muhsina Bintoon Yiasha, Gulam Sulaman Choudhury

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Chest disease is one of the most problematic ailments in our regular life. There are many known chest diseases out there. Diagnosing them correctly plays a vital role in the process of treatment. There are many methods available explicitly developed for different chest diseases. But the most common approach for diagnosing these diseases is through X-ray. In this paper, we proposed a multi-classification deep learning model for diagnosing COVID-19, lung cancer, pneumonia, tuberculosis, and atelectasis from chest X-rays. In the present work, we used the transfer learning method for better accuracy and fast training phase. The performance of three architectures is considered: InceptionV3, VGG-16, and VGG-19. We evaluated these deep learning architectures using public digital chest x-ray datasets with six classes (i.e., COVID-19, lung cancer, pneumonia, tuberculosis, atelectasis, and normal). The experiments are conducted on six-classification, and we found that VGG16 outperforms other proposed models with an accuracy of 95%.

Keywords: deep learning, image classification, X-ray images, Tensorflow, Keras, chest diseases, convolutional neural networks, multi-classification

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Authors: Suphap Sikkhaphan, Muwanga Zake, Johnnie Wycliffe Frank

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The purposes of the study included a) investigating the authentic and transformational leadership model of the directors of tambon health promoting hospitals b) evaluating the relation between the authentic and transformation leadership of the directors of tambon health promoting hospitals and the effectiveness of their hospitals and c) assessing the invariance test of the authentic and transformation leadership of the directors of tambon health promoting hospitals. All 400 southern tambon health promoting hospital directors were enrolled into the study. Half were males (200), and another half were females (200). They were sampled via a stratified method. A research tool was a questionnaire paper containing 4 different sections. The Alpha-Cronbach’s Coefficient was equally to .98. Descriptive analysis was used for demographic data, and inferential statistics was used for the relation and invariance tests of authentic and transformational leadership of the directors of tambon health promoting hospitals. The findings revealed overall the authentic and transformation leadership model of the directors of tambon health promoting hospitals has the relation to the effectiveness of the hospitals. Only the factor of “strong community support” was statistically significantly related to the authentic leadership (p < .05). However, there were four latent variables statistically related to the transformational leadership including, competency and work climate, management system, network cooperation, and strong community support (p = .01). Regarding the relation between the authentic and transformation leadership of the directors of tambon health promoting hospitals and the effectiveness of their hospitals, four casual variables of authentic leadership were not related to those latent variables. In contrast, all four latent variables of transformational leadership has statistically significantly related to the effectiveness of tambon health promoting hospitals (p = .001). Furthermore, only management system variable was significantly related to those casual variables of the authentic leadership (p < .05). Regarding the invariance test, the result found no statistical significance of the authentic and transformational leadership model of the directors of tambon health promoting hospitals, especially between male and female genders (p > .05).

Keywords: authentic leadership, transformational leadership, tambon health promoting hospital

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Authors: Lok Raj Joshi, Naveen Prakash Shah, Sharad Kumar Sharma, I. Ratna Bhattarai, Rajendra Basnet, Deepak Dahal, Bahagwan Maharjan, Seraphine Kaminsa

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Context: Tuberculosis (TB) is a significant health issue in Nepal, a country with a high burden of the disease. Despite efforts to control TB, there is still a gap in the notification of TB cases, which hinders effective control and treatment. This paper aims to address this notification gap and proposes strategies to improve TB control in Nepal. Research Aim: The aim of this research is to understand and address the tuberculosis notification gap in Nepal. The focus is on enhancing the healthcare system, involving the private sector and communities, raising awareness, and addressing social determinants to achieve sustainable TB control. Methodology: The research methodology involved a review of existing epidemiological data and research studies related to TB in Nepal. Additionally, consultation with an expert group from the TB control program in Nepal provided insights into the current state of TB control and challenges in addressing the notification gap. Findings: The findings reveal that only 55% of TB cases were reported in 2022, indicating a significant notification gap. Of the reported cases, only 32% and 19% were referred by the private sector and community, respectively. Furthermore, 20% of diagnosed cases were not treated in the initial phase. The estimated number of cases of multidrug-resistant TB (MDR TB) was 2,800, suggesting a low diagnosis rate. Among the diagnosed MDR TB cases, only 60% were receiving treatment. Additionally, it was observed that 20% of diagnosed MDR TB cases were from India and not enrolling in TB treatment in Nepal, indicating a high rate of defaulters. Theoretical Importance: The study highlights the importance of adopting a holistic strategy to address the notification gap in TB cases in Nepal. It emphasizes the need to enhance healthcare infrastructure, raise awareness, involve the private sector and local communities, establish effective methods to trace initial defaulters, implement TB interventions in border regions, and mitigate the social stigma associated with the disease. Data Collection and Analysis Procedures: Data for this study was collected through a review of existing epidemiological data and research studies. The data were then analyzed to identify patterns, trends, and gaps in TB case notification in Nepal.

Keywords: TB, tuberculosis, private sector, community, migrants, nepal

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Authors: Ren-Jye Lin, Li-Hsiung Lin, Bing-Cheng Liu, Ching-Len Liao

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The human zinc finger protein 36-like protein family, containing zinc finger protein 36-like 1 (ZFP36L1) and zinc finger protein 36-like 2 (ZFP36L2), belongs to CCCH-type zinc-finger protein identified as an RNA-binding protein that participates in controlling posttranscriptional regulation via RNA decay pathways. Recently, we demonstrated that human ZFP36L1 showed potent antiviral activity against flavivirus Infection by both 5´-3´ XRN1 and 3´-5´RNA-exosome RNA decay pathways (Journal of Virology 2022 Jan 12;96(1): e0166521). However, another zinc finger protein 36-like protein member, ZFP36L2, in the host defense response against flaviviruses has yet to be addressed. Here, we also demonstrate that ZFP36L2 functions as a host innate defender against flaviviruses, including Japanese encephalitis virus (JEV) and dengue virus (DENV). Overexpression of ZFP36L2 reduced JEV and DENV infection, and ZFP36L2 knockdown significantly promoted viral replication. Distinct from the antiviral mechanism of ZFP36L1, ZFP36L2 inhibits flavivirus infection by only a 5´-3´ XRN1-mediated RNA decay pathway but not the 3´-5´RNA-exosome RNA decay pathway. Human ZFP36L1 and ZFP36L2 can restrict flavivirus replication by directly binding and destabilizing viral RNA. Thus, for the first time, human zinc finger protein 36-like family members, ZFP36L1 and ZFP36L2, are identified as host antiviral factors that can bind and degrade flavivirus viral RNA by diverse antiviral mechanisms.

Keywords: ZFP36L1, ZFP36L2, 5'-3' exonuclease XRN1, antiviral mechansim

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