Overall survival of nasopharyngeal carcinoma (NPC) at UICC stage IV still remains unsatisfactory even with combination chemotherapy (CT) and radio-therapy (RT). In view of the association of reactivation of Epstein-Barr virus (EBV) with the development and recurrence of NPC, immunotherapy in the form of transfer factor (TF) with specific activity against EBV (TF-B1) was suggested as an adjuvant to a combination of CT and RT in order to improve survival. In the present study, 6 UICC stage IV patients received TF-B1 and another 6 patients matched for disease stage were given TF prepared from peripheral blood leucocytes (TF-PBL). Results were compared with another 18 patients matched by age, sex, and stage of disease who received standard therapy without TF during the same period (C group). After a median follow up of 47.5 months, the survival for the TF-B1 group was found to be significantly better (P = < 0.05) than the PBL and C group. While the 8 patients with distant metastasis (DM), not treated with TF-B1 (6 in the control and 2 in the PBL group), died due to progressive disease (average survival being 14.3 months), both patients with DM in the TF-B1 group had complete remission: one died of tuberculosis after surviving for 3.5 years and another is still alive, disease free, after 4.2 years. Although the series involved a small number of cases, the apparent effect of adjuvant immunotherapy in the form of TF with anti-EBV activity is of considerable interest.
The aim of this study was to determine the incidence and outcome of herpes zoster hospitalised children with cancer in Kota Baru. It was a retrospective review from January 1994 to December 1998. The diagnosis of herpes zoster was a clinical one. Herpes zoster was diagnosed in 10 of 188 (5%) children with malignancy. The most common malignancy was leukaemia. Nine children were treated with acyclovir. No child developed visceral dissemination and there were no deaths.
Matched MeSH terms: Antiviral Agents/therapeutic use
We describe two cases of transfusion dependent thalassaemics with chronic hepatitis C virus infection whom were treated successfully with interferon and ribavirin, following failure of response or relapse after an initial response to interferon monotherapy. They had sustained virological response for more than twelve months after completing therapy. Transfusion requirements were significantly increased during the combination therapy, probably due to ribavirin-induced haemolysis. Serum ferritin level decreased significantly during the treatment. Combination therapy with interferon alfa and ribavirin may be a feasible treatment option for some nonresponders to prior interferon monotherapy.
Four to 6 months of conventional interferon alpha (IFN-alpha) (5MU daily or 10MU three times weekly) resulted in HBeAg loss in approximately 33% of HBeAg positive patients (controls: 12%). Longer treatment duration improved HBeAg seroconversion. Children with chronic HBV infection and high ALT respond to IFN-a at similar rates. Good end-of-treatment (ET) biochemical and virological response were also achieved with IFN-alpha in HBeAg negative, HBV-DNA positive hepatitis patients. Sustained response (SR) however, was disappointing, but improved with longer duration of treatment: (10-15% SR with 4/6 months treatment: 30% SR with 24 months treatment). Weekly pegylated IFN-alpha2a (PegIFN-alpha2a) for 24 weeks gave a significantly higher HBeAg conversion rate (33%) than conventional IFN-alpha2a (25%). Fifty-two weeks of PegIFN-alpha2b gave a sustained HBeAg loss in 35% patients and HBeAg seroconversion in 29% patients. Similar results were obtained with 48 weeks of weekly PegIFN-alpha2a. PegIFN-alpha2a monotherapy was found to be superior to lamivudine monotherapy in affecting a 6-month SR (normal ALTs and HBV DNA < 20,000 copies/mL) in HBeAg negative/anti-HBe positive chronic hepatitis B patients. There is a tendency for IFN-a and lamivudine combination to result in better sustained response than lamivudine monotherapy. This tendency is also observed with PegIFN-a and lamivudine combination although the combination did not appear to be better than PegIFN-alpha monotherapy. IFN induced HBeAg seroconversion is durable, could increase over time and resulted in better overall survival and survival free of hepatic decompensation or hepatocellular cancer. The main advantage of IFN-a therapy is that a course of finite duration may achieve sustained off-therapy response in a proportion of both HBeAg positive and HBeAg negative chronic hepatitis B patients. However, IFN treatment is usually associated with side-effects, especially flu-like symptoms, fatigue, neutropenia, thrombocytopenia and depression. These are usually tolerable but may require dose modification and premature cessation of treatment (5%). Interferon therapy induced hepatitis flares may lead to decompensation in patients with cirrhosis and can be dangerous in patients with decompensated liver function despite dose reduction.
We describe a patient with HbE-beta thalassaemia and chronic hepatitis C virus infection (genotype 1a) who was treated successfully with peginterferon alfa-2b and ribavirin, following failure to respond to standard interferon and ribavirin therapy. She had sustained virological response for nearly 24 months after completing peginterferon alfa-2b and ribavirin therapy. Transfusion requirements were significantly increased during combination therapy due to ribavirin-induced haemolysis. The adverse effects of interferon were well tolerated. Combination therapy with peginterferon alfa-2b and ribavirin maybe a feasible treatment option for a subset of thalassaemia/HCV infected non-responders to standard interferon-based therapy.
Avian influenza, an infectious disease of birds, is caused by type A strain of the influenza virus. The disease, which was first identified in Italy more than 100 years ago, occurs worldwide. Avian influenza viruses are mainly distributed by migratory birds. Various animals like birds, pigs, horses, sea mammals and, finally, humans are susceptible to influenza A viruses. The high possibility of genomic changes like gene shift and drift are caused by the segmented RNA genome.
Matched MeSH terms: Antiviral Agents/therapeutic use
Within the past decade a number of new zoonotic paramyxoviruses emerged from flying foxes to cause serious disease outbreaks in man and livestock. Hendra virus was the cause of fatal infections of horses and man in Australia in 1994, 1999 and 2004. Nipah virus caused encephalitis in humans both in Malaysia in 1998/99, following silent spread of the virus in the pig population, and in Bangladesh from 2001 to 2004 probably as a result of direct bat to human transmission and spread within the human population. Hendra and Nipah viruses are highly pathogenic in humans with case fatality rates of 40% to 70%. Their genetic constitution, virulence and wide host range make them unique paramyxoviruses and they have been given Biosecurity Level 4 status in a new genus Henipavirus within the family Paramyxoviridae. Recent studies on the virulence, host range and cell tropisms of henipaviruses provide insights into the unique biological properties of these emerging human pathogens and suggest approaches for vaccine development and therapeutic countermeasures.
Matched MeSH terms: Antiviral Agents/therapeutic use
Acute retinal necrosis (ARN) is known to occur in conjunction with primary varicella or chickenpox infection. The majority of ARN cases reported in the literature were of milder form with mild to moderate vitritis, limited retinitis, and rare occurrence of retinal breaks or detachment that responded well to intravenous acyclovir, with or without oral prednisolone. We report a case of unilateral ARN with marked vitritis and retinal necrosis leading to retinal breaks following chickenpox in a 32-year-old healthy lady. This patient was successfully treated with intravenous acyclovir followed by oral acyclovir and orbital floor triamcinolone injections to contain the inflammation with barrier laser therapy to secure the retinal breaks with good visual outcome. This case is unusual in its severity, and to our knowledge, orbital floor triamcinolone therapy was not used earlier to contain ARN inflammation.
Matched MeSH terms: Antiviral Agents/therapeutic use
A 43-year-old lady with type 2 diabetes mellitus and bronchial asthma presented with varicella zoster infection, dyspnea, and neck fullness. An urgent computed tomography scan revealed a mediastinal abscess with superior vena cava thrombus. Blood, mediastinal pus, and swab from a vesiculopustule on the neck cultured group A beta hemolytic Streptococcus. She recovered with a combination of broad spectrum antimicrobials, antivirals, and surgical drainage. This case illustrates the rare occurrence of mediastinal abscess and acute superior vena cava obstruction caused by group A beta hemolytic Streptococcus complicating adult varicella zoster.
Matched MeSH terms: Antiviral Agents/therapeutic use
Dengue viruses, mosquito-borne members of the Flaviviridae family, are the causative agents of dengue fever and its associated complications, dengue haemorrhagic fever and dengue shock syndrome. To date, more than 2.5 billion people in over 100 countries are at risk of infection, and approximately 20 million infections were reported annually. There is currently no treatment or vaccine available for dengue infection. This study employed a whole-cell organism model or in vitro methods to study the inhibitory property of the flavanoid-derived compounds against DENV2 activity. Results showed that at concentration not exceeding the maximum non-toxic dose (MNTD), these compounds completely prevented DENV2 infection in HepG2 cells as indicated by the absence of cytophatic effects. The in vitro antiviral activity assessed in HepG2 cells employing virus inhibition assay showed high inhibitory activity in a dose dependent manner. At concentration below MNTD, compounds exhibited inhibitory activity against DENV2 with a range of potency strengths of 72% to 100%. The plaque forming unit per ml (pfu/ml) was reduced prominently with a maximum reduction of 98% when the infected HepG2 cells were treated with the highest non-toxic dose of compounds. The highly potent activity of the compounds against DENV2 infection strongly suggests their potential as a lead antiviral agent for dengue.
Matched MeSH terms: Antiviral Agents/therapeutic use
The 2009 pandemic influenza A(H1N1) infection in Malaysia was first reported in May 2009 and oseltamivir was advocated for confirmed cases in postexposure prophylaxis. However, there are cases of oseltamivir-resistance reported among H1N1-positive patients in other countries. Resistance is due to substitution of histidine by tyrosine at residue 275 (H275Y) of neuraminidase (NA). In this study, we have employed Sanger sequencing method to investigate the occurrence of mutations in NA segments of 67 pandemic 2009 A(H1N1) viral isolates from Malaysian patients that could lead to probable oseltamivir resistance. The sequencing analysis did not yield mutation at residue 275 for all 67 isolates indicating that our viral isolates belong to the wild type and do not confer resistance to oseltamivir.
Matched MeSH terms: Antiviral Agents/therapeutic use
We report a 57-year-old woman with a 20-year history of hepatitis B presenting with progressive proximal lower limb weakness for the previous 1 month. Previous medical history included a pericardial and pleural effusion, of which no cause was found and pulmonary tuberculosis which has been adequately treated. Examination revealed multiple telangiactasia over face and nail beds and bilateral proximal lower limb weakness of power 4/5. Biochemical investigation revealed a raised erythrocyte sedimentation rate of 36 mm/h, elevated creatinine kinase levels (14,363 IU/L) and raised liver enzymes (alanine aminotransferase 445 IU/L, aspartate aminotransferase 606 IU/L) with high hepatitis B virus DNA (1,021,158 copies/mL). Nerve conduction tests and muscle biopsy were consistent with polymyositis. She received entacavir for hepatitis B treatment. Despite treatment with entacavir for 10 weeks, her weakness persisted and prednisolone was added. Upon commencement of prednisolone, her symptoms and biochemical profiles returned to normal.
In recent years, several paramyxoviruses have emerged to infect humans, including previously unidentified zoonoses. Hendra and Nipah viruses (henipaviruses within this family) were first identified in the 1990s in Australia, Malaysia and Singapore, causing epidemics with high mortality and morbidity rates in affected animals and humans. Other paramyxoviruses, such as Menangle virus, Tioman virus, human metapneumovirus and avian paramyxovirus 1, which cause less morbidity in humans, have also been recently identified. Although the Paramyxoviridae family of viruses has been previously recognised as biomedically and veterinarily important, the recent emergence of these paramyxoviruses has focused our attention on this family. Antiviral drugs can be designed to target specific important determinants of the viral life cycle. Therefore, identifying and understanding the mechanistic underpinnings of viral entry, replication, assembly and budding will be critical in the development of antiviral therapeutic agents. This review focuses on the molecular mechanisms discovered and the antiviral strategies pursued in recent years for emerging paramyxoviruses, with particular emphasis on viral entry and exit mechanisms.
We examined the anti-influenza virus activity of tricin, 4',5,7-trihydroxy-3',5'-dimethoxyflavone, against five viruses: A/Solomon islands/3/2006 (H1N1), A/Hiroshima/52/2005 (H3N2), A/California/07/2009 (H1N1pdm), A/Narita/1/2009 (H1N1pdm) and B/Malaysia/2506/2004 strains in vitro and against A/PR/8/34 virus in vivo.
Dengue is a serious arboviral disease currently with no effective antiviral therapy or approved vaccine available. Therefore, finding the effective compound against dengue virus (DENV) replication is very important. Among the natural compounds, bioflavonoids derived mainly from plants are of interest because of their biological and medicinal benefits.