Diagnostic performance of GeneXpert MTB/RIF in detecting MTB in smear-negative presumptive TB patients.

BACKGROUND: Tuberculosis (TB) is a leading cause of morbidity and mortality worldwide. Control of TB is lingering by the lack of diagnostic tests that are simple, rapid, yet accurate. Thus, smear-negative pulmonary TB often misses the diagnosis. The study evaluated the performance of GeneXpert MTB/RIF assay for the detection of Mycobacterium tuberculosis (MTB). METHODS: The study was carried out from June to December 2016 in Nepal Tuberculosis Center, Bhaktapur, Nepal. A total of 173 sputum samples were collected and processed by microscopy [Auramine-O staining and Ziehl-Neelsen (ZN) staining], followed by GeneXpert MTB/RIF assay and culture in Lowenstein-Jensen (LJ) medium. RESULTS: Of 173 sputum samples, 162 (93.6%) were smear-negative. Of 162 smear-negative sputum samples, 35 (21.6%) were confirmed to have MTB by culture, and 31 (19.1%) by GeneXpert MTB/RIF assay. Of 31 GeneXpert-positive samples, 25 (80.6%) were susceptible, 4 (12.9%) were resistant, and 2 (6.45%) were intermediate to rifampicin. The sensitivity, specificity, positive predictive value, and negative predictive value of GeneXpert MTB/RIF assay for smear-negative sputum samples were 74.3%, 96.6%, 86.7%, and 92%, respectively. The GeneXpert MTB/RIF has a substantial diagnostic agreement of 90.91% with culture (Cohen's Kappa coefficient = 0.73). CONCLUSION: The diagnostic performance of GeneXpert MTB/RIF assay was almost on par with culture, and thus can be relied upon for MTB detection in smear-negative sputum samples.

Prevalence of carbapenemase-producing Klebsiella pneumoniae at a tertiary care hospital in Kathmandu, Nepal.

AIM: Although carbapenem is the last-resort drug for treating drug-resistant Gram-negative bacterial infections, prevalence of carbapenem-resistant bacteria has substantially increased worldwide owing to irrational use of antibiotics particularly in developing countries like Nepal.  Therefore, this study was aimed to determine the prevalence of carbapenemase-producing K. pneumoniae and to detect the carbapenemase genes (blaNDM-2 and blaOXA-48) in at a tertiary care hospital in Nepal. MATERIALS AND METHODS: A hospital-based cross-sectional study was carried out from June 2018 to January 2019 at the Microbiology Laboratory of Annapurna Neurological Institute and Allied Sciences, Kathmandu, Nepal. Different clinical samples were collected and cultured in appropriate growth media. Biochemical tests were performed for the identification of K. pneumoniae. Antibiotic susceptibility testing (AST) was performed by the Kirby-Bauer disc diffusion method. The modified Hodge test (MHT) was performed to detect carbapenemase producers. The plasmid was extracted by the modified alkaline hydrolysis method. Carbapenemase-producing K. pneumoniae were further confirmed by detecting blaNDM-2 and blaOXA-48 genes by PCR using specific forward and reverse primers followed by gel electrophoresis. RESULTS: Out of the total 720 samples, 38.9% (280/720) were culture positive. K. pneumoniae was the most predominant isolate 31.4% (88/280). Of 88 K. pneumoniae isolates, 56.8% (50/88) were multi-drug resistant (MDR), and 51.1% (45/88) were MHT positive. Colistin showed the highest sensitivity (100%; 88/88), followed by tigecycline (86.4%; 76/88). blaNDM-2 and blaOXA-48 genes were detected in 24.4% (11/45) and 15.5% (7/45) of carbapenemase-producing K. pneumoniae isolates, respectively. CONCLUSION: The rate of MDR and carbapenemase production was high in the K. pneumoniae isolates. Colistin and tigecycline could be the drug of choice for the empirical treatments of MDR and carbapenemase-producing K. pneumoniae. Our study provides a better understanding of antibiotic resistance threat and enables physicians to select the most appropriate antibiotics.

Acute Infection of Viral Pathogens and Their Innate Immune Escape.

Viral infections can cause rampant disease in human beings, ranging from mild to acute, that can often be fatal unless resolved. An acute viral infection is characterized by sudden or rapid onset of disease, which can be resolved quickly by robust innate immune responses exerted by the host or, instead, may kill the host. Immediately after viral infection, elements of innate immunity, such as physical barriers, various phagocytic cells, group of cytokines, interferons (IFNs), and IFN-stimulated genes, provide the first line of defense for viral clearance. Innate immunity not only plays a critical role in rapid viral clearance but can also lead to disease progression through immune-mediated host tissue injury. Although elements of antiviral innate immunity are armed to counter the viral invasion, viruses have evolved various strategies to escape host immune surveillance to establish successful infections. Understanding complex mechanisms underlying the interaction between viruses and host's innate immune system would help develop rational treatment strategies for acute viral infectious diseases. In this review, we discuss the pathogenesis of acute infections caused by viral pathogens and highlight broad immune escape strategies exhibited by viruses.

Induction of the Antiviral Immune Response and Its Circumvention by Coronaviruses.

Some coronaviruses are zoonotic viruses of human and veterinary medical importance. The novel coronavirus, severe acute respiratory symptoms coronavirus 2 (SARS-CoV-2), associated with the current global pandemic, is characterized by pneumonia, lymphopenia, and a cytokine storm in humans that has caused catastrophic impacts on public health worldwide. Coronaviruses are known for their ability to evade innate immune surveillance exerted by the host during the early phase of infection. It is important to comprehensively investigate the interaction between highly pathogenic coronaviruses and their hosts. In this review, we summarize the existing knowledge about coronaviruses with a focus on antiviral immune responses in the respiratory and intestinal tracts to infection with severe coronaviruses that have caused epidemic diseases in humans and domestic animals. We emphasize, in particular, the strategies used by these coronaviruses to circumvent host immune surveillance, mainly including the hijack of antigen-presenting cells, shielding RNA intermediates in replication organelles, 2'-O-methylation modification for the evasion of RNA sensors, and blocking of interferon signaling cascades. We also provide information about the potential development of coronavirus vaccines and antiviral drugs.

Multiple social platforms reveal actionable signals for software vulnerability awareness: A study of GitHub, Twitter and Reddit.

The awareness about software vulnerabilities is crucial to ensure effective cybersecurity practices, the development of high-quality software, and, ultimately, national security. This awareness can be better understood by studying the spread, structure and evolution of software vulnerability discussions across online communities. This work is the first to evaluate and contrast how discussions about software vulnerabilities spread on three social platforms-Twitter, GitHub, and Reddit. Moreover, we measure how user-level e.g., bot or not, and content-level characteristics e.g., vulnerability severity, post subjectivity, targeted operating systems as well as social network topology influence the rate of vulnerability discussion spread. To lay the groundwork, we present a novel fundamental framework for measuring information spread in multiple social platforms that identifies spread mechanisms and observables, units of information, and groups of measurements. We then contrast topologies for three social networks and analyze the effect of the network structure on the way discussions about vulnerabilities spread. We measure the scale and speed of the discussion spread to understand how far and how wide they go, how many users participate, and the duration of their spread. To demonstrate the awareness of more impactful vulnerabilities, a subset of our analysis focuses on vulnerabilities targeted during recent major cyber-attacks and those exploited by advanced persistent threat groups. One of our major findings is that most discussions start on GitHub not only before Twitter and Reddit, but even before a vulnerability is officially published. The severity of a vulnerability contributes to how much it spreads, especially on Twitter. Highly severe vulnerabilities have significantly deeper, broader and more viral discussion threads. When analyzing vulnerabilities in software products we found that different flavors of Linux received the highest discussion volume. We also observe that Twitter discussions started by humans have larger size, breadth, depth, adoption rate, lifetime, and structural virality compared to those started by bots. On Reddit, discussion threads of positive posts are larger, wider, and deeper than negative or neutral posts. We also found that all three networks have high modularity that encourages spread. However, the spread on GitHub is different from other networks, because GitHub is more dense, has stronger community structure and assortativity that enhances information diffusion. We anticipate the results of our analysis to not only increase the understanding of software vulnerability awareness but also inform the existing and new analytical frameworks for simulating information spread e.g., disinformation across multiple social environments online.

Intestinal Parasitic Infections among Prison Inmates in Kathmandu Nepal.

BACKGROUND: Prison inmates are at high risk of intestinal parasitic infections. Thus, we studied intestinal parasitic infections among inmates of the Central Jail, Kathmandu, Nepal. METHODS: Morning stool samples from 400 inmates (M=282 and F=118), were collected in a clean, dry and wide-mouthed plastic container. The samples were transported to the research laboratory of Shi-Gan International College of Science and Technology, and were fixed using 10% formal saline. Then, samples were processed by formal ether sedimentation concentration technique and were observed microscopically by direct-smear technique. RESULTS: Six percent (24/400) samples were positive for intestinal parasites, with a gender ratio (M:F) 1.7:1. But, co-parasitism was not observed. Intestinal parasitic infections were higher among 21-40 years age-group, 3.5% (14/262). Similarly, intestinal parasitic infections were higher among 'Dalits' ethnic group, 21.1% (4/19). As compared to helminths, more protozoans, 62.5% (15/24), were observed. Giardia lamblia, 41.67% (10/24), was the most common protozoans while Trichuris trichiura, 25.0% (6/24), was the most common helminths. CONCLUSIONS: Intestinal parasitic infections were lower among the inmates of Central jail, but such conditions cannot be presumed in other peripheral settings. Pure and safe drinking water supply and the effective deworming campaign can further reduce this figure at this setting and peripheral jails across the country.

Diarrheal disease outbreak in Gaidatar village of Rautahat District, Nepal.

OBJECTIVE: Diarrheal diseases, including cholera, remain a major public health concern in developing countries like Nepal. This study investigated a diarrheal outbreak that affected over 1500 people in Gaidatar village of Rautahat district in central Nepal and sought to identify the source and causation of the disease. Stool samples were collected from individuals with acute diarrheal illness (n = 16) and healthy non-diarrheal children (n = 39), along with samples from local drinking water sources (n = 8) and their sewage system (n = 10). None of the individuals were sampled multiple times. Diarrheic stool and sewage samples were analysed for the presence of Vibrio cholerae, while coliforms were tested in drinking water samples following standard microbiological protocols. Enteric parasites were tested in both diarrheic and non-diarrheic stool samples. RESULTS: Vibrio cholerae O1 Ogawa serotype was isolated in 18.7% of the diarrheic stool and 20.0% of the sewage. Coliforms were found in all drinking water samples, with 87.5% testing positive for fecal coliform. Additionally, 43.6% of the stool samples (n = 55) had at least one of the intestinal parasites tested, primarily Giardia lamblia (21.8%). However, almost all parasites were found in non-diarrheal stool. Taken together, our results provide evidence that the diarrheal outbreak was associated with V. cholerae O1 Ogawa serotype, possibly transmitted through the drinking water sources contaminated with fecal matters from their sewage (drainage) system. These findings warrant regular surveillance of drinking water sources to help prevent future outbreaks.