Demographic and clinical variables in the dengue epidemic in Punjab, Pakistan.

Objectives: To identify the latest trends in the clinical picture and severity of the disease, which will help better understand and manage dengue. Methodology: It was a cross-sectional, hospital-based study performed in the tertiary care hospitals of Punjab from August 21 to December 2022, in which serologically and polymerase chain reaction (PCR) confirmed patients with dengue infection, were enrolled. Demographic and clinical variables were recorded on a pre-tested Performa, processed and presented in frequency and percentages, and graphs were generated. Mean and standard deviation was used to present continuous variables. Results: Out of a total of 580 patients, 472 were diagnosed with Dengue Fever (DF) and 108 with Dengue Hemorrhagic Fever (DHF). About 79.31% of the patients were male and 20.69% were females. The mean age of patients was 32.5±9 years. Among the clinical features the percentage of high-grade fever, body aches, and vomiting were the highest. The liver function profile showed that serum bilirubin, Serum aspartate transaminase (AST), serum alanine transaminase (ALT,) and alkaline phosphatase (ALP) levels were markedly raised. Conclusion: This study showed that with time the trends in the presentation of dengue are slowly shifting, which will help us better manage the disease burden in the future.

Novel mutations in structural proteins of dengue virus genomes.

BACKGROUND: Genomic characterization of the dengue virus (DENV) is useful for understanding its molecular evolution, transmission, pathogenicity and infectivity. The DENV genomic RNA encodes three structural proteins, capsid (C) envelope (E) and membrane (M) proteins mediating viral entry and assembly during host infection. The current study aims to explore the DENV serotypes and mutations in the E and M proteins. METHODS: Twenty-three samples of DENV-positive patients were processed and selected for whole genome sequencing (WGS) from the Punjab Province of Pakistan. RESULTS: Among the 23 WGS, 19 samples showed numerous mutations (BioProject ID PRJNA943555). DENV1 and DENV2 are the most prevalent serotypes. A total of 179 mutations were detected in the E protein, in which K203E, T88A, I114L, and I293T are novel. The I270L, T272A, S273L, and T277A were found in the "kl" ß-hairpin (aa 270-279). The M protein harbors 74 mutations, of which 24 were novel. Three prominent complementary regions in the prM and E protein complex formations include R6, E46, D47, D63, and D65 on 'pr' peptide, and E84, K64, and H244, K247 on E, remain conserved except R6C. To our knowledge, it is the first comprehensive study of mutations in structural proteins. CONCLUSION: Genomic epidemiology is critical for analyzing emerging mutations and designing new policies therapeutic efforts for future outbreaks.

Emerging role of macrophages in non-infectious diseases: An update.

In the past three decades, a huge body of evidence through various research studies conducted on animal models, has demonstrated that the macrophages are centralized of all the leukocytes involved in diseases and, particularly, their role in non-infectious diseases has been studied extensively for which they have also been referred to as the "double-edged swords". The most versatile of all immunocytes, macrophages play a key role in health and diseases. Various experimental models have demonstrated the conventional paradigms such as the M1/M2 dichotomy, which is not as obvious and presents a complex characterization of the macrophages in the disease immunology. In human diseases, this M1-M2 continuum shows a complex web of mechanisms, which are majorly divided into the pro-inflammatory roles (derived mainly by the cytokines: IL-1, IL-6, IL-12, IL-23, and tumor necrosis factor) and anti-inflammatory roles (CCl-17, CCl-22, CCL-2, transforming growth factor (TGF), and interleukin-10), which are involved in the wound healing and pathogen-suppression. The conventional division of these macrophages as M1 and M2 is derived from the opposing functions of these macrophages; where M1 is involved in the tissue damage and pro-inflammatory roles and M2 promotes cell proliferation and the resolution of inflammation. Both these pathways down-regulate each other in diseases through a plethora of enzymatic and cytokine mediators.