Mycobacterium avium complex (MAC) is a major cause of non-tuberculous pulmonary and disseminated diseases worldwide, inducing bronchiectasis, and affects HIV and immunocompromised patients. In MAC, Mycobacterium avium subsp. hominissuis is a pathogen that infects humans and mammals, and that is why it is a focus of this study. It is crucial to find essential drug targets to eradicate the infections caused by these virulent microorganisms. The application of bioinformatics and proteomics has made a significant impact on discovering unique drug targets against the deadly pathogens. One successful bioinformatics methodology is the use of in silico subtractive genomics. In this study, the aim was to identify the unique, non-host and essential protein-based drug targets of Mycobacterium avium subsp. hominissuis via in silico a subtractive genomics approach. Therefore, an in silico subtractive genomics approach was applied in which complete proteome is subtracted systematically to shortlist potential drug targets. For this, the complete dataset of proteins of Mycobacterium avium subsp. hominissuis was retrieved. The applied subtractive genomics method, which involves the homology search between the host and the pathogen to subtract the non-druggable proteins, resulted in the identification of a few prioritized potential drug targets against the three strains of M. avium subsp. Hominissuis, i.e., MAH-TH135, OCU466 and A5. In conclusion, the current study resulted in the prioritization of vital drug targets, which opens future avenues to perform structural as well as biochemical studies on predicted drug targets against M. avium subsp. hominissuis.
Previous exposures to flu and subsequent immune responses may impact on 2009/2010 pandemic flu vaccine responses and clinical symptoms upon infection with the 2009 pandemic H1N1 influenza strain. Qualitative and quantitative differences in humoral and cellular immune responses associated with the flu vaccination in 2009/2010 (pandemic H1N1 vaccine) and natural infection have not yet been described in detail. We designed a longitudinal study to examine influenza- (flu-) specific immune responses and the association between pre-existing flu responses, symptoms of influenza-like illness (ILI), impact of pandemic flu infection, and pandemic flu vaccination in a cohort of 2,040 individuals in Sweden in 2009–2010. Cellular flu-specific immune responses were assessed by whole-blood antigen stimulation assay, and humoral responses by a single radial hemolysis test. Previous seasonal flu vaccination was associated with significantly lower flu-specific IFN-γ responses (using a whole-blood assay) at study entry. Pandemic flu vaccination induced long-lived T-cell responses (measured by IFN-γ production) to influenza A strains, influenza B strains, and the matrix (M1) antigen. In contrast, individuals with pandemic flu infection (PCR positive) exhibited increased flu-specific T-cell responses shortly after onset of ILI symptoms but the immune response decreased after the flu season (spring 2010). We identified non-pandemic-flu vaccinated participants without ILI symptoms who showed an IFN-γ production profile similar to pandemic-flu infected participants, suggesting exposure without experiencing clinical symptoms. Strong and long-lived flu-M1 specific immune responses, defined by IFN-γ production, in individuals after vaccination suggest that M1-responses may contribute to protective cellular immune responses. Silent flu infections appeared to be frequent in 2009/2010. The pandemic flu vaccine induced qualitatively and quantitatively different humoral and cellular immune responses as compared to infection with the 2009 H1N1 pandemic H1N1 influenza strain.
Dengue fever is a vector-borne, acute, febrile, and self-limiting systemic viral infection that affects tropical and subtropical regions, including Pakistan. Karachi has a significant burden of Aedes aegypti and Aedes albopictus due to suitable breeding sites, weather, and rapid and unplanned urbanization of squatter areas. The country has limited surveillance studies on circulating serotypes of the dengue virus and the patient's clinical features evolving over temporal changes. This study aimed to bridge the gap by screening 1500 patients using immunochromatographic detection and clinically following up on 486 of them. RNA extraction and cDNA synthesis of positive patients were performed, followed by PCR and sequencing. Data analysis and graphs were done on Prism 8.0. Males (53.87%) had a higher infection rate than females (46.13), with ages 18-60 years having the highest infection rate (69.14%). Results showed that 57.8% of patients were positive for NS1, followed by IgM (39.8%), and IgG (89.77%). DENV 1 and DENV 2 were found to be circulating, representing 20% and 80% respectively. Data on fever, shortness of breath, body aches, headache, nausea, vomiting, diarrhea, and epistaxis revealed significant differences. We conclude that continuous surveillance of dengue and other Flaviviruses and their infections is necessary to improve the prognosis and management of vector-borne diseases, thereby reducing the associated mortality rate of patients in Pakistan.