Pneumococcal carriage and changes in serotype distribution post- PCV13 introduction in children in Matiari, Pakistan.

Background: In early 2021, the 10-valent Pneumococcal conjugate vaccine (PCV10) was replaced with 13-valent (PCV13) by the federal directorate of immunization (FDI), Pakistan. We assessed the impact of a higher valent vaccine, PCV13, on the serotype distribution of nasopharyngeal carriage in rural Pakistan.

Methods: Children <2 years were randomly selected from two rural union councils of Matiari, Sindh in Pakistan between September-October,2022.

Evolution of COVID-19 infection in Punjab; trends during five waves of infection in the province of Punjab.

Background: Pakistan witnessed five waves of COVID-19 infections during the pandemic. Punjab, the largest province of Pakistan, remained the epicentre due to a high infection rate. Administrative data for five waves of the pandemic was analyzed to determine the rate of infections and the significance of pharmacological and non-pharmacological interventions on the severity and duration of infection.

Strain features of pneumococcal isolates in the pre- and post-PCV10 era in Pakistan.

Pakistan is amongst the four countries with the highest number of pneumococcal deaths. While the PCV10 vaccine was introduced in Pakistan in October 2012, data regarding the impact of the vaccine on the population dynamics of in Pakistan remain obscure. Using whole genome sequencing of 190 isolates (nasopharyngeal carriage=75, disease=113, unknown sites=2) collected between 2002 and 2020, this study presents characteristics of pneumococcal strains in Pakistan in the pre- and post-vaccine era.

Regional and National Trends in Consumption of Antimicrobials in Pakistan; Pre and Post-COVID (2019-2021).

Background: Efforts to combat antimicrobial resistance, a growing public health problem in Pakistan, have been hampered by the lack of high-quality national and provincial-level antimicrobial consumption data. The singular objective of this retrospective study was to measure antimicrobial consumption over 3 years between 2019 and 2021.

Methods: The study was designed to estimate antimicrobial consumption at National and Regional levels.

Spontaneous NETosis in diabetes: A role of hyperglycemia mediated ROS and autophagy.

Type 2-diabetes, particularly poorly controlled diabetes, is a risk factor for several infections such as lower respiratory tract and skin infections. Hyperglycemia, a characteristic downstream effect of poorly controlled diabetes, has been shown to impair the function of immune cells, in particular neutrophils. Several studies have demonstrated that hyperglycemia-mediated priming of NADPH oxidase results in subsequent elevated levels of reactive oxygen species (ROS).

Raman spectroscopy and machine learning-based optical probe for tuberculosis diagnosis via sputum.

Tuberculosis (TB) is a contagious disease that causes 1.5 million deaths per year globally. Early diagnosis of TB patients is critical to control its spread.

Emergence of a multidrug-resistant and virulent Streptococcus pneumoniae lineage mediates serotype replacement after PCV13: an international whole-genome sequencing study.

Background: Serotype 24F is one of the emerging pneumococcal serotypes after the introduction of pneumococcal conjugate vaccine (PCV). We aimed to identify lineages driving the increase of serotype 24F in France and place these findings into a global context.

Methods: Whole-genome sequencing was performed on a collection of serotype 24F pneumococci from asymptomatic colonisation (n=229) and invasive disease (n=190) isolates among individuals younger than 18 years in France, from 2003 to 2018.

Trends in antimicrobial resistance amongst pathogens isolated from blood and cerebrospinal fluid cultures in Pakistan (2011-2015): A retrospective cross-sectional study.

While antimicrobial resistance (AMR) continues to be a major public health problem in Pakistan, data regarding trends of resistance among pathogenic bacteria remains scarce, with few studies presenting long-term trends in AMR. This study was therefore designed to analyze long-term AMR trends at a national level in Pakistan. We report here results of a comprehensive analysis of resistance, among pathogens isolated from blood and cerebrospinal fluid (CSF), between 2011 and 2015.

Host biomarkers for monitoring therapeutic response in extrapulmonary tuberculosis.

Purpose: The aim of this study was to explore the utility of inflammatory biomarkers in the peripheral blood to predict response to treatment in extrapulmonary tuberculosis (EPTB).

Methods: A Luminex xMAP-based multiplex immunoassay was used to measure 40 inflammatory biomarkers in un-stimulated plasma of 91 EPTB patients (48 lymphadenitis, and 43 pleuritis) before and at 2 and 6 months of treatment.

Results: Overall a significant change was observed in 28 inflammatory biomarkers with treatment in EPTB patients.

An evaluation of lipid profile and pro-inflammatory cytokines as determinants of cardiovascular disease in those with diabetes: a study on a Mexican American cohort.

Sedentary life styles coupled with high-calorie diets and unhealthy social habits such as smoking, have put an ever-increasing number of people at risk of cardiovascular disorders (CVD), worldwide. A concomitant increase in the prevalence of type 2-diabetes (hyperglycemia), a risk factor for CVD, has further contributed towards escalating CVD-related mortalities. The increase in number of cases of type 2-diabetes underscores the importance of early diagnosis of cardiovascular disease in those with diabetes.

An Engineered Microvirin Variant with Identical Structural Domains Potently Inhibits Human Immunodeficiency Virus and Hepatitis C Virus Cellular Entry.

Microvirin (MVN) is one of the human immunodeficiency virus (HIV-1) entry inhibitor lectins, which consists of two structural domains sharing 35% sequence identity and contrary to many other antiviral lectins, it exists as a monomer. In this study, we engineered an MVN variant, LUMS1, consisting of two domains with 100% sequence identity, thereby reducing the chemical heterogeneity, which is a major factor in eliciting immunogenicity. We determined carbohydrate binding of LUMS1 through NMR chemical shift perturbation and tested its anti-HIV activity in single-round infectivity assay and its anti-hepatitis C virus (HCV) activity in three different assays including HCVcc, HCVpp, and replicon assays.

PspA facilitates evasion of pneumococci from bactericidal activity of neutrophil extracellular traps (NETs).

Pneumococcal strains are variably resistant to killing by neutrophil extracellular traps (NETs). We hypothesize that this variability in resistance is due to heterogeneity in pneumococcal surface protein A (PspA), a structurally diverse virulence factor of Streptococcus pneumoniae. Pneumococcal strains showed variability in induction of NETs and in susceptibility to killing by NETs.

Estimation of hepatitis C prevalence in the Punjab province of Pakistan: A retrospective study on general population.

Background: Hepatitis C virus (HCV) infections are amongst the leading public health concerns in Pakistan with a high disease burden. Despite the availability of effective antiviral treatments in the country the disease burden in general population has not lowered. This could be attributed to the asymptomatic nature of this infection that results in lack of diagnosis until the late symptomatic stage.

Evolution of efficacious pangenotypic hepatitis C virus therapies.

Hepatitis C compromises the quality of life of more than 350 million individuals worldwide. Over the last decade, therapeutic regimens for treating hepatitis C virus (HCV) infections have undergone rapid advancements. Initially, structure-based drug design was used to develop molecules that inhibit viral enzymes.

The effects of differences in pspA alleles and capsular types on the resistance of Streptococcus pneumoniae to killing by apolactoferrin.

Pneumococcal surface protein A (PspA) is the only pneumococcal surface protein known to strongly bind lactoferrin on the bacterial surface. In the absence of PspA Streptococcus pneumoniae becomes more susceptible to killing by human apolactoferrin (apo-hLf), the iron-free form of lactoferrin. In the present study we examined diverse strains of S.

Infection and cellular defense dynamics in a novel 17β-estradiol murine model of chronic human group B streptococcus genital tract colonization reveal a role for hemolysin in persistence and neutrophil accumulation.

Genital tract carriage of group B streptococcus (GBS) is prevalent among adult women; however, the dynamics of chronic GBS genital tract carriage, including how GBS persists in this immunologically active host niche long term, are not well defined. To our knowledge, in this study, we report the first animal model of chronic GBS genital tract colonization using female mice synchronized into estrus by delivery of 17β-estradiol prior to intravaginal challenge with wild-type GBS 874391. Cervicovaginal swabs, which were used to measure bacterial persistence, showed that GBS colonized the vaginal mucosa of mice at high numbers (10(6)-10(7) CFU/swab) for at least 90 d.

Meeting physical activity guidelines is associated with lower allostatic load and inflammation in Mexican Americans.

Examine the relationship between physical activity (PA) and allostatic load in Mexican-Americans as well as variations by gender. Self-reported PA as well as cardiovascular, metabolic and inflammatory markers were assessed in 330 Mexican-American adults in the Cameron County Hispanic Cohort (Brownsville, TX, USA). Dependent variables included total allostatic load, blood pressure, metabolic, and inflammatory scores.

Novel recombinant human lactoferrin: differential activation of oxidative stress related gene expression.

Lactoferrin, an iron-binding protein found in high concentrations in mammalian exocrine secretions, is an important component of the host defense system. It is also a major protein of the secondary granules of neutrophils from which is released upon activation. Due to its potential clinical utility, recombinant human lactoferrin (rhLF) has been produced in various eukaryotic expression systems; however, none of these are fully compatible with humans.

Impaired CD4+ and T-helper 17 cell memory response to Streptococcus pneumoniae is associated with elevated glucose and percent glycated hemoglobin A1c in Mexican Americans with type 2 diabetes mellitus.

Individuals with type 2 diabetes are significantly more susceptible to pneumococcal infections than healthy individuals of the same age. Increased susceptibility is the result of impairments in both innate and adaptive immune systems. Given the central role of T-helper 17 (Th17) and T-regulatory (Treg) cells in pneumococcal infection and their altered phenotype in diabetes, this study was designed to analyze the Th17 and Treg cell responses to a whole heat-killed capsular type 2 strain of Streptococcus pneumoniae.

Modified opsonization, phagocytosis, and killing assays to measure potentially protective antibodies against pneumococcal surface protein A.

The standard opsonophagocytosis killing assay (OPKA) for antibodies to pneumococcal capsular polysaccharide was modified to permit an evaluation of the protection-mediating antibodies to pneumococcal surface protein A (PspA). We found that by increasing the incubation time with the complement and phagocytes from 45 min to 75 min, the protective activity was readily detected. In another modification, we used a capsule type 2 target strain that expressed PspA but not pneumococcal surface protein C (PspC).

Pneumococcal surface protein A inhibits complement deposition on the pneumococcal surface by competing with the binding of C-reactive protein to cell-surface phosphocholine.

In the presence of normal serum, complement component C3 is deposited on pneumococci primarily via the classical pathway. Pneumococcal surface protein A (PspA), a major virulence factor of pneumococci, effectively inhibits C3 deposition. PspA's C terminus has a choline-binding domain that anchors PspA to the phosphocholine (PC) moieties on the pneumococcal surface.

PNPLA3 polymorphisms and liver aminotransferase levels in a Mexican American population.

Purpose: This study examined genetic associations of patatin-like phospholipase domain containing 3 gene (PNPLA3) polymorphisms and liver aminotransferases in an extensively documented, randomly recruited Mexican American population at high risk of liver disease.

Methods: Two single nucleotide polymorphisms (SNP) in the PNPLA3 gene (i.e.