The Zika outbreak of the 21st century.

The Zika virus outbreak has captivated the attention of the global audience and information has spread rapidly and wildly through the internet and other media channels. This virus was first identified in 1947, when it was isolated from a sentinel rhesus monkey placed by British scientists working at the Yellow Fever Research Laboratory located in the Zika forest area of Uganda, hence its name, and is transmitted primarily by the mosquito vector, Aedes aegypti. The fact that the rhesus macaque is an Asian species being placed in an African forest brings to mind the possibility of rapid adaptation of the virus from an African to Asian species, an issue that has not been considered. Whether such adaptation has played any role in acquiring pathogenicity due to cross species transmission remains to be identified. The first human infection was described in Nigeria in 1954, with only scattered reports of about a dozen human infections identified over a 50-year period. It was not until 2007 that Zika virus raised its ugly head with infections noted in three-quarters of the population on the tiny island of Yap located between the Philippines and Papua New Guinea in the western Pacific Ocean, followed by a major outbreak in French Polynesia in 2013. The virus remained confined to a narrow equatorial band in Africa and Asia until 2014 when it began to spread eastward, first toward Oceania and then to South America. Since then, millions of infected individuals have been identified in Brazil, Colombia, Venezuela, including 25 additional countries in the Americas. While the symptoms associated with Zika virus infection are generally mild, consisting of fever, maculopapular rash, arthralgia and conjunctivitis, there have been reports of more severe reactions that are associated with neurological complications. In pregnant women, fetal neurological complications include brain damage and microcephaly, while in adults there have been several cases of virus-associated Guillain-Barre syndrome. The virus was until recently believed to only be transmitted via mosquitoes. But when the Zika virus was isolated from the semen specimens from a patient in Texas, this provided the basis for the recent report of possible sexual transmission of the Zika virus. Due to the neurological complications, various vectors for infection as well as the rapid spread throughout the globe, it has prompted the World Health Organization to issue a global health emergency. Various governmental organizations have recommended that pregnant women do not travel to countries where the virus is epidemic, and within the countries affected by the virus, recommendations were provided for women of childbearing age to delay pregnancy. The overall public health impact of these above findings highlights the need for a rapid but specific diagnostic test for blood banks worldwide to identify those infected and for the counseling of women who are pregnant or contemplating pregnancy. As of this date, there are neither commercially licensed diagnostic tests nor a vaccine. Because cross-reactivity of the Zika virus with dengue and Chikungunya virus is common, it may pose difficulty in being able to quickly develop such tests and vaccines. So far the most effective public health measures include controlling the mosquito populations via insecticides and preventing humans from direct exposure to mosquitoes

Evaluation of cloud based approaches to data quality management

Quality of data is critical for making data driven business decisions. Enhancing the quality of data enables companies to make better decisions and prevent business losses. Systems similar to Extract Transform and Load (ETL) are often used to clean and improve the quality of data. Currently, businesses tend to collect a massive amount of customer data, store it in the cloud, and analyze the data to gain statistical inferences about their products, services, and customers. Cheaper storage, constantly improving approaches to data privacy and security provided by cloud vendors, such as Microsoft Azure, Amazon Web Service, seem to be the key driving forces behind this process. This thesis implements Azure Data Factory based ETL system that serves the purpose of data quality management in the Microsoft Azure Cloud platform. In addition to Azure Data Factory, there are four other key components in the system: (1) Azure Storage for storing raw, and semi cleaned data; (2) HDInsight for processing raw and semi cleaned data using Hadoop clusters and Hive queries; (3) Azure ML Studio for processing raw and semi cleaned data using R scripts and other machine learning algorithms; (4) Azure SQL database for storing the cleaned data. This thesis shows that using Azure Data factory as the core component offers many benefits because it helps in scheduling jobs, and monitoring the whole data transformation processes. Thus, it makes data intake process more timely, guarantees data reliability, simplifies data auditing. The developed system was tested and validated using sample raw data

Impaired IFN-γ Production by Viral Immunodominant Peptide-specific Tetramer+ CD8+ T Cells in HIV-1 Infected Patients is not Secondary to HAART

Studies on PBMC samples from HIV-1 infected patients have shown that despite substantial number of HIV specific CTLs, these patients gradually progress to AIDS. The present study was conducted to determine whether this paradox was secondary to the influence of protease inhibitors being utilized by these patients. Thus, aliquots of PBMC samples from 10 HIV infected humans with no prior history of anti-retroviral drug therapy (ART) and 6 HIV-infected patients that had been on HAART for >1 year were analyzed for the frequency of HIV-1 Nef and Gag dominant peptide specific tetramer+ cells, respectively. The tetramer+ PBMCs were analyzed for their ability to synthesize specific peptide induced IFN-γ utilizing both the ELISPOT and the intracellular cytokine (ICC) assays. Results of the studies showed that there was an overall correlation between the frequency of Nef and Gag peptide tetramer+ cells and the frequency of IFN-γ synthesizing cells as assayed by either ICC or ELISPOT assay, markedly reduced values of IFN-γ synthesizing cells per unit tetramer+ cells were noted in both group of patients. These data suggest that the frequency of HIV-specific CD8+T cells is maintained during the chronic phase of infection, their ability to function is compromised and is not a reflection of ART. While the addition of IL-2, anti-CD40L and allogeneic cells led to partial increase in the ability of the tetramer+ cells to synthesize IFN-γ, the addition of IL-4, IL-12, anti-CD28 or a cocktail of anti-TGF-β, TNF-α and IL-10 failed to augment the IFN-γ response

Genetic Analysis of Cytokine Promoters in Nonhuman Primates: Implications for Th1/Th2 Profile Characteristics and SIV Disease Pathogenesis

The shift from a predominant synthesis of prototype Th1 cytokines to Th2 or Th0 type of cytokines by antigen activated PBMC's from HIV infected humans and SIV infected disease susceptible rhesus macaques (RM) has been shown to be associated with disease progression. Paradoxically, antigen activated PBMC's from sooty mangabeys (SM), which are naturally infected with SIV and are disease resistant despite high viral loads, maintain a predominant Th2 cytokine profile. It has been reasoned that the resistance to perturbations of cytokine synthesis by slow and/or nonprogressor HIV infected patients and SIV infected disease susceptible RM is secondary to inherited polymorphisms within the promoter regions for cytokines. Similar promoter polymorphisms could also contribute to the cytokine profile of PBMC's from SM. To address this issue promoter regions for the major Th1/Th2 cytokines from RM and SM were cloned and sequenced. Sequence analysis of promoter fragments of IL-4, IL-10, IL-12 p40, IFN-gamma and TNF-alpha from the two monkey species showed varying degree of homology ranging from high degree of homology detected for IFN-gamma promoter (>99%) to relatively high degree of polymorphism detected for TNF-alpha promoter (94% homology). In addition, several variable regions within the promoters of IL-12 p40, IL-10 and TNF-alpha in the two species contain polymorphisms in sequences that constitute binding sites of known transcription factors (TF). Such differences are likely to differentially bind TF and thus either qualitatively and/or quantitatively affect the regulation of cytokine synthesis in these two species and potentially contribute to disease progression and/or resistance

Recommendations for coronavirus infection in rheumatic diseases treated with biologic therapy.

The Coronavirus-associated disease, that was first identified in 2019 in China (CoViD-19), is a pandemic caused by a bat-derived beta-coronavirus, named SARS-CoV2. It shares homology with SARS and MERS-CoV, responsible for past outbreaks in China and in Middle East. SARS-CoV2 spread from China where the first infections were described in December 2019 and is responsible for the respiratory symptoms that can lead to acute respiratory distress syndrome. A cytokine storm has been shown in patients who develop fatal complications, as observed in past coronavirus infections. The management includes ventilatory support and broad-spectrum antiviral drugs, empirically utilized, as a targeted therapy and vaccines have not been developed. Based upon our limited knowledge on the pathogenesis of CoViD-19, a potential role of some anti-rheumatic drugs may be hypothesized, acting as direct antivirals or targeting host immune response. Antimalarial drugs, commonly used in rheumatology, may alter the lysosomal proteases that mediates the viral entry into the cell and have demonstrated efficacy in improving the infection. Anti-IL-1 and anti-IL-6 may interfere with the cytokine storm in severe cases and use of tocilizumab has shown good outcomes in a small cohort. Baricitinib has both antiviral and anti-inflammatory properties. Checkpoints inhibitors such as anti-CD200 and anti-PD1 could have a role in the treatment of CoViD-19. Rheumatic disease patients taking immunosuppressive drugs should be recommended to maintain the chronic therapy, prevent infection by avoiding social contacts and pausing immunosuppressants in case of infection. National and international registries are being created to collect data on rheumatic patients with CoViD-19

Genetic Characterization of Carbapenem Resistant Acinetobacter baumannii in Tertiary care settings of Lahore, Pakistan

Background: Acinetobacter baumannii is major cause of ventilator associated pneumoniae (VAP) as it is an opportunistic nosocomial organism. The current study was to find out the antibiotic resistance pattern of Acinetobacter baumannii, its phenotype and the genetic characterization of Metallo-β-Lactamase (MBL) genes that are responsible for carbapenem resistance.Methods: One hundred and fifty Carbapenem resistant Acinetobacter baumannii (CRAB) specimens were isolated and PCR amplification of organism specific bla-OXA-51gene was performed and antibiotic susceptibility was checked. Phenotypic susceptibility analysis was performed by Modified Hodge Test (MHT) and Imipenem-EDTA Double Disc Synergy Test (IMP-EDTA DDST). The carbapenemases and MBL producing genes were amplified by PCR.Results: CRAB showed high resistance against piperacillin/tazobactam (99.3%), cefepime and ceftazidime (99.3% each), amikacin (91.3%), ciprofloxacin (96.7%) and levofloxacin (96.7%). Only one isolate showed resistance to colistin. The isolates positive for both MHT and DDST (n=70) were further characterized to detect metallo-β-lactamase genes. Molecular characterization revealed the presence of bla-OXA-51 gene in all tested isolates (100%) followed by bla-VIM 89%, bla-OXA-23 64%, respectively and so on. Few genes coexisted with each other including bla VIM, bla OXA 23, bla OXA 51 and bla NDM-1.  None of the isolate was found positive for bla-IMP gene.Conclusion: It is concluded that CRAB isolates exhibited a high rate of resistance towards antimicrobials because of the presence of drug hydrolyzing enzymes, carbapenemases and MBLs. This is among the rare study reported recently indicating CRAB isolates co-harboring many resistant genes are very difficult to treat. There is a dire need to develop novel antibiotics against resistant A. baumannii to minimize its prevalence. Moreover, it is recommended that colistin treatment in the clinical settings should be continuously monitored in order to prevent the development of resistance

The Search for a Practical Approach to Emerging Diseases: The Case of Severe Acute Respiratory Syndrome (SARS)

The plague, which the Board of Health had feared might enter with the German troops into the Milanese, had entered it indeed, as is well known; and it is likewise well known, that it paused not here, but invaded and ravaged a great part of Italy. (A. Manzoni, The Bethrothed, 1826

Studies on the potential use of CD38 expression as a marker for the efficacy of anti-retroviral therapy in HIV-1-infected patients in Thailand

AbstractThe monitoring of the efficacy of anti-retroviral therapy (ART) is becoming an important issue in the developing world. The current use of CD4 counts, plasma viral loads, and monitoring of drug-resistant viruses are at present either uninformative or costly. Thus, more new cost-effective and practical techniques need to be established and implemented. Towards this goal, our lab has carried out studies on the potential use of CD38 frequency and density expression by flow analysis as a means to assess the efficacy of ART. Results of our studies using whole blood sample from normal healthy donors indicate that CD38 is expressed by a high frequency of not only CD4+ and CD8+ T cells but also most hematopoietic cell lineages analyzed. Detailed studies of CD38 expression along with other cell surface markers using whole blood sample from HIV-1-infected patients showed that the most discriminating change was the increased frequency and density of CD38 expression by CD3+CD8+ T cells. Of importance was our preliminary finding that a reversal of the increased frequency and density of CD38 expression by CD8+ T cells only appeared in the whole blood sample from patients who were responders to ART but not those who were drug failures. These initial data provide a platform and incentive for larger cohort studies including prospective pre- and post-ART for the institution of such monitoring techniques in resource limited settings