More than10 million people are suffering from hepatitisC virus(HCV) inPakistan.The available treatment option is a combination of interferon and ribavirin.Treatment response is linked with several factors and also induces a number of side effects.We searched inPubmed,PakMedi Net andGoogleScholar for the articles presenting the effect of interferon plus ribavirin therapy onHCV patients fromPakistan, their side effects and future prospects.The major prevalent HCV genotype inPakistan is3.Conventional interferon alpha plus ribavirin showed sustained virological response of54%-64% while pegylated interferon alpha plus ribavirin showed sustained virological response of58%-75%.IL-28BCC genotype is linked with better sustained virological response.Studies on patients withHCV genotype3 infections showed no correlation between treatment response and interferon sensitivity determining region mutations.Interferon therapy is linked with a number of side effects like thyroid dysfuncton, haematological disorders, weight loss, gastrointestinal tractside effects and neuropsychiatric side effects.Unusual side effects of clubbing of fingers and seizures were also observedin a couple of patients.Interferon alpha plus ribavirin therapy showed better response rate inHCV genotype3 patients fromPakistan with number of side effects.A couple of interferon free therapies are light of hope for the patients living withHCV.

More than 10 million people are suffering from hepatitis C virus (HCV) in Pakistan. The available treatment option is a combination of interferon and ribavirin. Treatment response is linked with several factors and also induces a number of side effects. We searched in Pubmed, Pak Medi Net and Google Scholar for the articles presenting the effect of interferon plus ribavirin therapy on HCV patients from Pakistan, their side effects and future prospects. The major prevalent HCV genotype in Pakistan is 3. Conventional interferon alpha plus ribavirin showed sustained virological response of 54%-64% while pegylated interferon alpha plus ribavirin showed sustained virological response of 58%-75%. IL-28B CC genotype is linked with better sustained virological response. Studies on patients with HCV genotype 3 infections showed no correlation between treatment response and interferon sensitivity determining region mutations. Interferon therapy is linked with a number of side effects like thyroid dysfuncton, haematological disorders, weight loss, gastrointestinal tract side effects and neuropsychiatric side effects. Unusual side effects of clubbing of fingers and seizures were also observed in a couple of patients. Interferon alpha plus ribavirin therapy showed better response rate in HCV genotype 3 patients from Pakistan with number of side effects. A couple of interferon free therapies are light of hope for the patients living with HCV.

Objective: To determine hepatitis C virus (HCV) genotypes and explore the associated risk factors in chronic HCV patients. Methods:A total of 116 patients with chronic hepatitis C were subjected to polymerase chain reaction (PCR) based detection out of which 112 chronic HCV patients [53 male (47.32%), 59 female (52.68%);mean age (43.76±16.40) years;mean BMI (23.8±3.9) kg] were enrolled in this study. The frequency of 6 HCV genotypes and associated risk factors were evaluated from five districts of North West Frontier Province (NWFP). Results:Genotype 3 was the most prevalent in 73 samples (65.17%) followed by genotype 1 in 24 (21.42%) and genotype 2 in 13 (11.60%) samples. Genotype 3 had significantly high prevalence (P=0.000 2). The results showed that 48 (42.85%) samples were infected with HCV 3a;25 (22.32%) with 3b;14 (12.50%) with 1a;10 (8.92%) with 1b; 11 (9.82%) with 2a; 2 (1.78%) with 2b;and 2 were untypable. The distribution of HCV genotypes in Mardan, Charsadda, Peshawar, Sawabi and Nowshehra districts was different. Use of unsterile equipment for medication, barbers and previous history of hospitalization were the main risk factors for HCV transmission. Conclusions:Genotype 3a and 3b, 1a, 1b and 2a are the common genotypes in NWFP. Genotype 4, 5, and 6 can not be found in a single sample. The level of awareness about various modes of transmission of HCV among the population is found to be very low.

West Africa is facing the worst Ebola outbreak with 3 685 cases and 1 841 deaths reported from Liberia, Guinea, Senegal, Sierra Leona and Nigeria. There is no vaccine or direct treatment available to treat the patients with Ebola. World Health Organization (WHO) has approved the use of experimental drugs for Ebola patients. Health workers are at high risk. The governments and WHO are responsible to provide necessary protective equipment to health workers dealing with Ebola. There is a strong need to identify the invisible chains of virus transmission. World Bank pledges $200 million to fight against Ebola, while WHO said $430 million are needed to control the Ebola outbreak. Ebola can be contained by early detection and isolation of case, contact tracing, monitoring of contacts and adaptation of rigorous procedures for virus control.

Acute promyelocytic leukemia (APML) is considered to be sensitive to all-trans-retinoic acid (ATRA) which acts as a differentiating agent. ATRA is considered to be a well-tolerated agent and is known to achieve complete remission in acute promyelocytic leukemia. However, a few cases on long term all-trans-retinoic acid (ATRA) use can develop pseudotumor cerebri. Out of 32 patients with APML who were treated in our Centre over a 4-year-period, we encountered 6 patients who developed ATRA-related pseudotumor cerebri while on maintenance treatment. The patients ranged from 12 to 40 years of age. 3 patients complained of unbearable headache, 2 of diplopia and 1 of gross reduction in visual acuity. CT scans and MRI did not reveal any intracranial lesions. Cerebrospinal fluid (CSF) examination was normal with CSF manometry revealing a high CSF pressure (average of 345mmH2O). Fundoscopy revealed papilledema in 5 patients and optic atrophy in 1 patient. The patients were successfully managed with decrease dose/discontinuation of ATRA, use of acetazolamide, corticosteroids and therapeutic CSF drainage.

BACKGROUNDHepatitis C virus (HCV) constitutes a major public health issue around the world, especially in developing countries like Pakistan. In this study, we assessed outcome of interferon (INF) treatment in chronic hepatitis C patients categorized by gender, age, and viral load.

METHODSIn this study, 750 HCV positive patients with genotype 3 were selected, out of which 616 completed the entire treatment. Their personal history, pre-treatment HCV RNA and serum alanine transaminase (ALT) was quantified. Patients were treated with combination therapy of INF-α 2b three million units (thrice a week) plus ribavirin (1000 - 1200 mg per day) for 24 weeks. After 24 weeks their HCV RNA and serum ALT level was quantified.

RESULTSOut of the 616 patients, 391 (63.5%) responded to therapeutic regimen (INF-α 2b plus ribavirin). Among the responders, 27.1% were men and 36.4% were women. Best treatment response was observed in patients having low viral load < 8 × 10(5) IU/ml and age ≤ 40 years than patients having low viral load and age > 40 years (73.2% vs. 60.3%, P = 0.05).

CONCLUSIONSBetter response to IFN-α 2b plus ribavirin was observed in patients with lower viral RNA and younger age. It suggests that all patients considered for treatment should have quantification of serum HCV RNA level. The result can be used to counsel patients on the likelihood of response and may influence the patient's decision on treatment.

Adult ; Antiviral Agents ; therapeutic use ; Female ; Genotype ; Hepatitis C, Chronic ; drug therapy ; virology ; Humans ; Interferon-alpha ; therapeutic use ; Male ; Pakistan ; Polymerase Chain Reaction ; RNA, Viral ; genetics ; Ribavirin ; therapeutic use ; Treatment Outcome

The current Zika outbreak is largest of its kind with 1.4 million cases in Brazil alone. World Health Organization declared the current outbreak as the public health emergency of international concerns. The major route of Zika virus transmission is mosquito bites. Sexual transmission and monkey bites are also observed in few cases. There is dire need to evaluate the other routes of transmission like blood transfusion, lactation and contact with body fluids. Zika virus is infecting infants, not only causing microcephaly but also creating number of complications resulting in bad outcomes of pregnancy. In Brazil alone, 4 000 cases of microcephaly have observed during the current outbreak. The incidence of Guillain-Barre (GB) syndrome is also observed during the current Zika virus outbreak. GB syndrome is acute medical condition leading the patients to death due to weakness of respiratory muscles or can cause the life time disability. There is no anti-viral drug or vaccine available for Zika virus. Zika infection can be prevented by using mosquito repellents, mosquito nets, cooling rooms by air conditions and wearing full sleeves or permethrin-treated clothes. The current outbreak of Zika has not only affected the health care but also caused great economic loss. Estimated loss in Latin America and Caribbean is US$3.5 billion. United Nation's sustainable development goal 3.d stresses the strengthening of early warning, risk reduction and management of national and global health risks. The world will keep on facing new challenges in the form of Ebola or Zika; there is strong need to prepare ourselves for any disease outbreak.

Objective: To evaluate the in-hospital outcome of moderate to severe COVID-19 patients admitted in High Dependency Unit (HDU) in relation to invasive vs. non-invasive mode of ventilation. Methods: In this study, the patients required either non-invasive [oxygen ≤10 L/min or >10 L/min through mask or nasal prongs, rebreather masks and bilevel positive airway pressure (BiPAP)] or invasive ventilation. For analysis of 30-day in hospital mortality in relation to use of different modes of oxygen, Kaplan Meier and log rank analyses were used. In the end, independent predictors of survival were determined by Cox regression analysis. Results: Invasive ventilation was required by 15.1% patients while 84.9% patients needed non-invasive ventilation. Patients with evidence of thromboembolism, high inflammatory markers and hypoxemia mainly required invasive ventilation. The 30-day in hospital mortality was 72.7% for the invasive group and 12.9% for the non-invasive group (1.8% oxygen <10 L/min, 0.9% oxygen >10 L/min, 3.6% rebreather mask and 4.5% BiPAP). The median time from hospital admission to outcome was 7 days for the invasive group and 18 days for the non-invasive group (P<0.05). Age, presence of co-morbidities, number of days requiring oxygen, rebreather, BiPAP and invasive ventilation were independent predictors of outcome. Conclusions: Invasive mechanical ventilation is associated with adverse outcomes possibly due to ventilator associated lung injury. Thus, protective non-invasive ventilation remains the necessary and safe treatment for severely hypoxic COVID-19 patients.

Objective To explore RNA dependent RNA polymerase of Chikungunya virus (CHIKV) and develop T cell based epitopes with high antigenicity and good binding affinity for the human leukocyte antigen (HLA) classes as targets for epitopes based CHIKV vaccine. Methods In this study we downloaded 371 non-structural protein 4 protein sequences of CHIKV belonging to different regions of the world from the US National Institute of Allergy and Infectious Diseases (NIAID) virus pathogen resource database. All the sequences were aligned by using CLUSTALW software and a consensus sequence was developed by using Uni Pro U Gene Software version 1.2.1. Propred I and Propred software were used to predict HLA I and HLA II binding promiscuous epitopes from the consensus sequence of non-structural protein 4 protein. The predicted epitopes were analyzed to determine their antigenicity through Vaxijen server version 2.0. All the HLA I binding epitopes were scanned to determine their immunogenic potential through the Immune Epitope Database (IEDB). All the predicted epitopes of our study were fed to IEDB database to determine whether they had been tested earlier. Results Twenty two HLA class II epitopes and eight HLA class I epitopes were predicted. The promiscuous epitopes WMNMEVKII at position 486–494 and VRRLNAVLL at 331–339 were found to bind with 37 and 36 of the 51 HLA class II alleles respectively. Epitope MANRSRYQS at position 58–66 and epitopes YQSRKVENM at positions 64–72 were predicted to bind with 12 and 9 HLA II alleles with antigenicity scores of 0.754 9 and 1.013 0 respectively. Epitope YSPPINVRL was predicted to bind 18 HLA I alleles and its antigenicity score was 1.425 9 and immunogenicity score was 0.173 83. This epitope is very useful in the preparation of a universal vaccine against CHIKV infection. Conclusions Epitopes reported in this study showed promiscuity, antigenicity as well as good binding affinity for the HLA classes. These epitopes will provide the baseline for development of efficacious vaccine for CHIKV.

Objective To predict immunogenic promiscuous T cell epitopes from the polyprotein of the Zika virus using a range of bioinformatics tools. To date, no epitope data are available for the Zika virus in the IEDB database. Methods We retrieved nearly 54 full length polyprotein sequences of the Zika virus from the NCBI database belonging to different outbreaks. A consensus sequence was then used to predict the promiscuous T cell epitopes that bind MHC 1 and MHC II alleles using PorPred1 and ProPred immunoinformatic algorithms respectively. The antigenicity predicted score was also calculated for each predicted epitope using the VaxiJen 2.0 tool. Results By using ProPred1, 23 antigenic epitopes for HLA class I and 48 antigenic epitopes for HLA class II were predicted from the consensus polyprotein sequence of Zika virus. The greatest number of MHC class I binding epitopes were projected within the NS5 (21%), followed by Envelope (17%). For MHC class II, greatest number of predicted epitopes were in NS5 (19%) followed by the Envelope, NS1 and NS2 (17% each). A variety of epitopes with good binding affinity, promiscuity and antigenicity were predicted for both the HLA classes. Conclusion The predicted conserved promiscuous T-cell epitopes examined in this study were reported for the first time and will contribute to the imminent design of Zika virus vaccine candidates, which will be able to induce a broad range of immune responses in a heterogeneous HLA population. However, our results can be verified and employed in future efficacious vaccine formulations only after successful experimental studies.