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Pakistan has the second highest hepatitis C virus (HCV) prevalence with seroprevalence of 4.5-8.2%, with genotype 3a being most frequently circulating HCV genotype. Current treatment strategies for HCV are based on direct acting antivirals (DAAs), despite high efficacy of antivirals, still therapy failure has been reported in 5-10% cases due to resistance mutations of amino acids. This study was aimed to analyze clinically important resistance associated mutations (RAMs) to daclatasvir (DCV) in HCV GT- 3a NS5A region in treatment naive and DAA treatment experienced patients, to understand their role in treatment failure. Patients samples and data was collected on prescribed questionnaire. Viral nucleic acid was isolated and amplified by gene specific primers followed by sequencing of NS5A region by Sanger method. Amino acid substitutions were identified by using Geno2Pheno tool. Hepatitis c virus genotype 3a was most prevalent genotype in the study group. Successfully sequenced patients were divided into two group based on their treatment history, as treatment naive and experienced groups. Both groups were analyzed for detection of amino acid mutations at positions 28, 30, 31, 58 and 93. A30T was detected in 7.6%, Y93H in 15.6% P58T as 7.6% while S98G was found in 23% treated patients. However, these mutations were not detected in any of treatment naive patients. Some mutations were identified in both treatment naive and experienced groups i.e., A21T, T64A, H85Y, S103P, D172E, H180N, T183A/V, and E137G. Mutations at position 62 was most commonly detected found at the frequency of 83.8% and 84.6% in treatment naive and experienced patients respectively. While mutations at position M28 and L31 were not identified in both groups of current study. Mutations present in both treatment naive as well as in treatment experienced groups suggesting they have no role in DCV resistance, while identification of A30T, Y93H, P58T and S98G in treated patients suggests that DCV RAMs are circulating in Pakistani HCV GT-3a DAAs treated patients, leading to resistance development and treatment failure. Identification of these mutations is important especially in treatment failure patients to design re-treatment strategies. [ABSTRACT FROM AUTHOR]

The current COVID-19 pandemic is caused by the novel SARS-CoV-2 coronavirus strain. Although SARS-CoV-2 infection can affect everyone, the kind and degree of infection and sickness vary widely between individuals and populations. It has been crucial since reported disease loads and case fatality rates vary greatly among countries. However, there are still uncertainties about the severity of the illness in certain people and, in other cases, the aetiology of a more severe illness. Various chronic conditions, such as diabetes, cardiovascular diseases, respiratory ailments, and immunodeficiency disorders, have been identified as significant risk factors for COVID-19. These comorbidities not only increase the susceptibility to contracting the virus but also exacerbate the severity of symptoms and the likelihood of adverse outcomes, including hospitalization, intensive care unit admission, and mortality. The objective of this article is to point out the proliferation of COVID-19 in relation to different diseases affecting the clinical outcome of COVID-19. The study included 1500 patients with various diseases such as HCV, HBV, kidney disease, heart disease, asthma, T.B., arthritis, smokers, and vaccinated or unvaccinated. Results showed that 22% of diabetic patients, 40% of heart patients, 40% of asthma patients, 26% of kidney patients, 25% of T.B patients, and 41% of smokers had high corona positive. Coronavirus positivity was found in 34% of vaccinated patients and 72% of non-vaccinated patients, with an overall calculated p-value of 0.0001 by ANOVA statistical analysis. The overall outcome of the results showed that the severity of Corona disease increased in relation to different diseases. [ABSTRACT FROM AUTHOR]

Abstract Background This study is based on EPI (Expanded Program on Immunization) immunization surveys and surveillance of polio, its challenges in immunization and the way forward to overcome these challenges. Methods Several Government documents, survey reports and unpublished program documents were studied and online search was made to find information on EPI Pakistan. SPSS 16 and Microsoft Excel 2007 were used for the statistical analysis. Results Immunization against polio is higher in urban areas as compared to rural areas. Marked variation in vaccination has been observed in different provinces of Pakistan in the last decade. Secondly 10-20% of the children who have received their first dose of trivalent polio vaccine were deprived of their 2nd and 3rd dose because of poor performance of EPI and Lack of information about immunization. Conclusion In spite of numerous successes, such as the addition of new vaccines and raising immunization to over 100% in some areas, EPI is still struggling to reach its polio eradication goals. Inadequate service delivery, lack of information about immunization and limited number of vaccinators were found to be the key reason for poor performance of immunization and for large number of cases reported each year due to the deficiency of second and third booster dose.

Abstract Background and Aims HCV infection may lead to hepatic fibrosis. In this study, we tried to determine whether there is any correlation of HCV genotypes and viral load to the clinical parameters such as ALT, AST, ALP, bilirubin, Hb level, patient's age and gender; and then correlated this association with disease progression in liver biopsy samples. Methods In cross-sectional and observational study, 6048 serum HCV RNA positive patients were chosen. The study consists of 53 months from March 2006 to September 2010. Patients were divided into three cohorts to validate our data. Statistical analysis and correlation of lab parameters with viral factors was determined by using SPSS version 16. Results The most prevalent genotype was 3 (70.9%) followed by 1 (13.3%) and 4 (7.4%), collectively. During Univariate analysis, in all cohorts; serum bilirubin, ALP, ALT and AAR showed significant correlation with genotypes, however multivariate analysis showed that all genotypes except 4a have no association with host biochemical markers. Disease progression was also independent of all genotypes. Serum ALP, ALT, bilirubin and viremea levels were significantly elevated in patients with genotype 4a. Viral load showed negative association with serum bilirubin (r = -0.112, P = 0.000) and ALP levels (r = -0.098, P = 0.000). We observed positive correlation of ALP and bilirubin levels, while negative associations of viral load with HCV liver disease progression. Conclusion Disease progression seems independent of the genotypes. Relationship between ALP and bilirubin with viral load may be an attractive marker to guess disease progression in patients with hepatitis C.

Abstract Background The 9.6 kb long RNA genome of Hepatitis C virus (HCV) is under the control of RNA dependent RNA polymerase, an error-prone enzyme, for its transcription and replication. A high rate of mutation has been found to be associated with RNA viruses like HCV. Based on genetic variability, HCV has been classified into 6 different major genotypes and 11 different subtypes. However this classification system does not provide significant information about the origin of the virus, primarily due to high mutation rate at nucleotide level. HCV genome codes for a single polyprotein of about 3011 amino acids which is processed into structural and non-structural proteins inside host cell by viral and cellular proteases. Results We have identified a conserved NS4A protein sequence for HCV genotype 3a reported from four different continents of the world i.e. Europe, America, Australia and Asia. We investigated 346 sequences and compared amino acid composition of NS4A protein of different HCV genotypes through Multiple Sequence Alignment and observed amino acid substitutions C22, V29, V30, V38, Q46 and Q47 in NS4A protein of genotype 1b. Furthermore, we observed C22 and V30 as more consistent members of NS4A protein of genotype 1a. Similarly Q46 and Q47 in genotype 5, V29, V30, Q46 and Q47 in genotype 4, C22, Q46 and Q47 in genotype 6, C22, V38, Q46 and Q47 in genotype 3 and C22 in genotype 2 as more consistent members of NS4A protein of these genotypes. So the different amino acids that were introduced as substitutions in NS4A protein of genotype 1 subtype 1b have been retained as consistent members of the NS4A protein of other known genotypes. Conclusion These observations indicate that NS4A protein of different HCV genotypes originally evolved from NS4A protein of genotype 1 subtype 1b, which in turn indicate that HCV genotype 1 subtype 1b established itself earlier in human population and all other known genotypes evolved later as a result of mutations in HCV genotype 1b. These results were further confirmed through phylogenetic analysis by constructing phylogenetic tree using NS4A protein as a phylogenetic marker.

Abstract HIV (Human immunodeficiency virus) transmission has been reduced by protected sex and screening of blood products and other body fluids in the developed countries. It has been reported that Pakistan is at high risk of HIV/AIDS infection but presently the prevalence rate is considerably low. The number of reported cases of HIV/AIDS in Pakistan has been continuously increasing since 1987. By 2010 the total number of registered cases has reached to 6000 and this figure is on the rise with the passage of time. Some serious strategies must be implemented to control this deadly disease.

Abstract Background Hepatitis C can lead to liver fibrosis and cirrhosis. We compared readily available non-invasive fibrosis indexes for the fibrosis progression discrimination to find a better combination of existing non-invasive markers. Methods We studied 157 HCV infected patients who underwent liver biopsy. In order to differentiate HCV fibrosis progression, readily available AAR, APRI, FI and FIB-4 serum indexes were tested in the patients. We derived a new fibrosis-cirrhosis index (FCI) comprised of ALP, bilirubin, serum albumin and platelet count. FCI = [(ALP × Bilirubin) / (Albumin × Platelet count)]. Results Already established serum indexes AAR, APRI, FI and FIB-4 were able to stage liver fibrosis with correlation coefficient indexes 0.130, 0.444, 0.578 and 0.494, respectively. Our new fibrosis cirrhosis index FCI significantly correlated with the histological fibrosis stages F0-F1, F2-F3 and F4 (r = 0.818, p < 0.05) with AUROCs 0.932 and 0.996, respectively. The sensitivity and PPV of FCI at a cutoff value < 0.130 for predicting fibrosis stage F0-F1 was 81% and 82%, respectively with AUROC 0.932. Corresponding value of FCI at a cutoff value ≥1.25 for the prediction of cirrhosis was 86% and 100%. Conclusions The fibrosis-cirrhosis index (FCI) accurately predicted fibrosis stages in HCV infected patients and seems more efficient than frequently used serum indexes.

Abstract Background Chronic HCV is one of the major causes of morbidity and mortality in the present day world. The assessment of disease progression not only provides useful information for diagnosis and therapeutic supervision judgment but also for monitoring disease. Different invasive and non invasive methods are applied to diagnose the disease from initial to end stage (mild fibrosis to cirrhosis). Although, liver biopsy is still considered as gold standard to identify liver histological stages, an assessment of the disease development based on non-invasive clinical findings is also emerging and this may replace the need of biopsy in near future. This review gives brief insight on non-invasive methods currently available for predicting liver fibrosis in HCV with their current pros and cons to make easier for a clinician to choose better marker to assess liver fibrosis in HCV infected patients. Methods More than 200 studies regarding invasive and noninvasive markers available for HCV liver disease diagnosis were thoroughly reviewed. We examined year wise results of these markers based on their sensitivity, specificity, PPV, NPV and AUROCs. Results We found that in all non-invasive serum markers for HCV, FibroTest, Forn's Index, Fibrometer and HepaScore have high five-year predictive value but with low AUROCs (0.60~0.85) and are not comparable to liver biopsy (AUROC = 0.97). Even though from its beginning, Fibroscan is proved to be best with high AUROCs (> 0.90) in all studies, no single noninvasive marker is able to differentiate all fibrosis stages from end stage cirrhosis. Meanwhile, specific genetic markers may not only discriminate fibrotic and cirrhotic liver but also differentiate individual fibrosis stages. Conclusions There is a need of marker which accurately determines the stage based on simplest routine laboratory test. Genetic marker in combination of imaging technique may be the better non invasive diagnostic method in future.