Tropheryma whipplei the causative agent of Whipple disease, presents a diagnostic challenge due to its diverse symptomatology, including weight loss, abdominal pain, diarrhea, joint pain, fever, and occasionally neurological manifestations. Its resistance to fluoroquinolones complicates treatment further. Traditional methods for antibiotic susceptibility testing are ineffective as Tropheryma whipplei cannot be cultured in axenic media. To address this, we explored potential drug targets within its core genome as no drug targets from this bacterium have been studied so far. murE, a macrolide-resistant enzyme, emerged as a promising candidate exhibiting both resistance and drug target characteristics. We screened over 1,000 lead-like Ayurvedic compounds against the target enzyme UDP-N-acetylmuramyl-tripeptide synthetase and identified three promising candidates: (1) Ergost-5-en-3-ol (3beta,24xi), (2) [6]-Gingerdiol 3-monoacetate, and (3) Valtrate. DiffDock and GNINA rescoring yielded consistent binding strength rankings. Molecular dynamics simulations over 100 nanoseconds confirmed stable interactions with these compounds. ADMET analysis indicated low water solubility, but coupling with cyclodextrin SBE-β-CD improved solubility. None of the compounds showed hepatotoxic effects, though Valtrate exhibited AMES toxicity. Based on the favorable properties, we propose scaffold hopping and further in vitro/in vivo studies on [6]-Gingerdiol 3-monoacetate. Our findings offer potential avenues for combating T. whipplei infections, addressing the limitations posed by antibiotic resistance.

Antimicrobial resistance (AMR) is a significant public health concern globally, and Pakistan is no exception. The misuse and overuse of antibiotics, inadequate regulation of their sale, and a lack of awareness contribute to the rising levels of AMR in the country. study presents a detailed analysis of blood and urine samples collected in Pakistan over various periods, focusing on pathogen prevalence, gender distribution, and age-wise patterns. From January 2013 to 2017, the North region exclusively contributed to the blood sample dataset, with Salmonella emerging as the primary pathogen, particularly affecting infants and neonates. Subsequently, from January 2017 to December 2020, a significant dataset emerged from the North and Punjab regions, with Salmonella and E.coli prevalent across all age groups, notably impacting adults and infants. In the period from January 2021 to the present, blood samples predominantly originated from the North and Punjab regions, with Salmonella and E.coli remaining significant pathogens, affecting adults and the elderly. Regarding urine samples, from January 2013 to December 2017, E.coli was the dominant pathogen, with females showing a higher susceptibility to urinary tract infections (UTIs), particularly among the elderly. Similarly, from January 2017 to December 2020, E.coli remained predominant, with UTIs more prevalent in females and the elderly. In the most recent period, the North region significantly contributed to UTI cases, with E.coli remaining predominant and females exhibiting a higher susceptibility, especially among the elderly. This comprehensive analysis provides crucial insights into the epidemiology of blood and urinary tract infections in Pakistan, informing public health strategies and interventions aimed at addressing these health challenges.

The enduring SARS-CoV-2 pandemic necessitates robust tools for severity assessment. This study, conducted at Islamabad Diagnostic Center across Pakistan from January 2021 to August 2022, aimed to investigate hematological abnormalities among suspected SARS-CoV-2 subjects. Initial enrollment included 130,347 cases, with 53,078 confirmed positive and 77,269 negative. An additional 11,786 samples expanded the dataset to 142,133. The Omicron and Centaurus variants, in confirmed positive patients, exhibited a slightly higher frequency of hematological abnormalities (30.42%) than negative participants (27.01%). Notably, lymphocyte count reduction (40.95%) suggested its potential as an alternative diagnostic parameter for clinical COVID-19. Decreased levels of NA (37.99%), HGB (26.17%), MCV (20.60%), PLT (6.15%), and ALB (2.28%) were observed. Abnormally elevated NEU, CR, MONO, RBCs, WBC, and EOS levels affected 26.00%, 24.28%, 30.79%, 22.02%, 6.28%, and 5.53% of subjects, respectively. Comparatively, positive patients exhibited higher abnormal blood parameters—LYMP count (57.40%), NEU count (46.08%), EOS count (62.48%), MONO count (31.61%), RBC count (30.32%), ALC count (43.60%), CR count (30.91%), NA count (40.53%), CRP count (68.46%), and DD (63.08%) than negative counterparts. The study underscores lymphocytopenia’s potential as a cost-effective, early diagnostic biomarker for clinical COVID-19, preceding real-time PCR diagnosis. This supports its consideration in resource-limited settings for strategic screening and policy-making in the ongoing SARS-CoV-2 battle.

HMGB1 is nuclear non-histone protein and unique member of cytokines. In viral hepatitis infection HMGB1 serum level increases and translocates towards cytoplasm and extracellular spaces where it activates single stimulating hepatic stellate cell proliferation which induces fibrogenic protein expression and causes hepatocellular carcinoma. In this study, total 150 subjects were recruited to assess the association between HMGB1 SNPs and HBV. Three types of genotypes were found visible in rs3742305 of HMGB1; wild type homozygous GG with 65%, homozygous minor type CC with 6% and heterozygous minor type GC with 26% frequency distribution. High prevalence of GG genotype in the selected population presenting that GG genotype may have higher risk for susceptibility to HBV infection. Our results showed significant correlation of HMGB1 polymorphism with HBV infection in the selected Pakistani population.

Background: Hepatitis B (HB) and Hepatitis C (HC) viral infections, with 328 million cases globally, represent a significant disease burden. Currently, Pakistan has 3.88 million HB and 9.31 million HC cases. High-risk populations like refugees are disproportionately affected by these infections. The objectives of this study were to determine the seroprevalence of hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (anti-HCV) among Kashmiri refugees in Muzaffarabad, Pakistan, and to identify the key demographic and educational risk factors associated with the seroprevalence in this population. Methods: A cross-sectional study was conducted across eight refugee camps in the Muzaffarabad division, Pakistan. A six-membered team visited each camp to collect blood samples through venipuncture. The seroprevalence of HBsAg and anti-HCV was determined using rapid immunochromatographic test (ICT) kits. Results: A total of 550 sera samples were collected from the refugee population in Muzaffarabad. The overall seroprevalence was 5.82% (32/550) for HBsAg and 4.73% (26/550) for anti-HCV. A higher seroprevalence of HBsAg and anti-HCV was recorded among females 6.12% (15/245), and 6.53% (16/245), respectively, compared to males 5.75% (17/305), and 3.28% (10/305), respectively. A marked increase in seroprevalence of HBsAg and anti-HCV was noted with an increase in age: 1–10 (2.44%) and (2.44%), 41–50 (8.20%) and (6.56%), and 51–60 (8.93%) and (8.93%), respectively. Chi-square test revealed a statistically significant association between age and seroprevalence of HBsAg χ² (degrees of freedom (df):6, N = 550) = 27.22, p = 0.000, and HC χ² (df:6, N = 550) = 15.23, p = 0.019.The level of education impacted the seroprevalence of HBsAg and anti-HCV, resulting in a higher seroprevalence of HBsAg (6.9%) and anti-HCV (5.4%) among uneducated individuals compared to educated individuals (4.71%) and (3.99%), respectively. Conclusion: The seroprevalence of HBsAg and anti-HCV is high among the refugee population of Muzaffarabad, Pakistan. There is a need for the implementation of a robust vaccination program for HB as well as the establishing a hepatitis micro-elimination program among the Kashmiri refugee population of Muzaffarabad, Pakistan.