Respiratory viral infections in the elderly

Viral respiratory infections represent a significant challenge for those interested in improving the health of the elderly. Influenza continues to result in a large burden of excess morbidity and mortality. Two effective measures, inactivated influenza vaccine, and the antiviral drugs rimantadine and amantadine, are currently available for control of this disease. Inactivated vaccine should be given yearly to all of those over the age of 65, as well as younger individuals with high-risk medical conditions and individuals delivering care to such persons. Live, intranasally administered attenuated influenza vaccines are also in development, and may be useful in combination with inactivated vaccine in the elderly. The antiviral drugs amantadine and rimantadine are effective in the treatment and prevention of influenza A, although rimantadine is associated with fewer side-effects. Recently, the inhaled neuraminidase inhibitor zanamivir, which is active against both influenza A and B viruses, was licensed for use in uncomplicated influenza. The role of this drug in treatment and prevention of influenza in the elderly remains to be determined. Additional neuraminidase inhibitors are also being developed. In addition, to influenza, respiratory infections with respiratory syncytial virus, parainfluenza virus, rhinovirus, and coronavirus have been identified as potential problems in the elderly. With increasing attention, it is probable that the impact of these infections in this age group will be more extensively documented. Understanding of the immunology and pathogenesis of these infections in elderly adults is in its infancy, and considerable additional work will need to be performed towards development of effective control measures.     

Oseltamivir: new preparation. An antiviral agent with little impact on influenza

(1) Oseltamivir, an oral antiviral agent, has been marketed in the European Union for the prevention and treatment of suspected influenza during epidemics. (2) Three prevention trials done in the general population showed moderate effects, with a 3.5-4% reduction (in absolute values) in serologically confirmed episodes of 'flu. According to one trial, oseltamivir was moderately effective as a prophylactic for close contacts of 'flu cases (6.6% in absolute values). (3) There are three placebo-controlled double-blind trials evaluating oseltamivir as a treatment for 'flu, two in adults and one in children. (4) At a dose of 75 mg twice a day, oseltamivir shortened symptoms by about 24 hours. There was no evidence that oseltamivir prevented complications that need antibiotic therapy. Influenza virus isolates from adult patients belonged to type A in more than 90% of cases. There is no sound evidence that oseltamivir is effective against type B influenza virus. (5) There was no reduction in the frequency of complications in a trial in at-risk adults with chronic respiratory or cardiovascular disorders, or in a trial in asthmatic children. (6) Patients receiving oseltamivir in clinical trials were more likely to suffer nausea and vomiting than patients given placebo. (7) Oseltamivir has not been compared with oral amantadine or inhaled zanamivir. (8) It is best to use amantadine when prophylaxis is needed during epidemics. In the curative setting, the poor risk-benefit ratio of oseltamivir, zanamivir, and amantadine, argues against the use of these drugs.     

Combating influenza with antiviral therapy in the pediatric population

Influenza viruses are accountable for annual epidemics worldwide that result in significant morbidity and mortality. In preschool and school-aged children, prospective surveillance of influenza demonstrates yearly infection rates of 15-42%. Children can easily transmit the virus to other children, to employees in day-care and school settings, and to family members. Two classes of antiviral drugs, the adamantine derivatives (amantadine, rimantadine) and neuraminidase inhibitors (zanamivir and oseltamivir), have been approved for treatment and prophylaxis of influenza in the pediatric population. Duration of clinical symptoms decreases and daily activities are resumed sooner when therapy is begun within 48 hours of the onset of influenza symptoms. Mechanism of action, adverse effects, and development of resistant variants differ between the two drug classes. To our knowledge, head-to-head clinical trials between the classes and involving the neuraminidase inhibitors are nonexistent. Antiviral agents do not replace the annual influenza vaccine, and clinical trials indicate that amantadine, rimantadine, zanamivir, and oseltamivir are safe and effective for administration in the pediatric population.     

Antivirals for influenza: what is their role in the older patient?

Influenza infection is a cause of high morbidity and mortality in the elderly living in the community or in long-term care facilities. Yearly immunisation is the most important means for prevention of infection. However, protection by vaccination in the elderly is incomplete, and influenza infections and outbreaks in long-term care facilities still occur. Symptoms of influenza include fever, chills, headache, myalgia and respiratory symptoms. These clinical features overlap considerably with other co-circulating respiratory viruses such as respiratory syncytial virus and parainfluenza virus. Elderly and debilitated patients with influenza may present with less prominent respiratory symptoms and may present only with fever, lassitude and confusion. Antiviral prophylaxis and treatment with amantadine and rimantadine have been given in the past but adverse effects and early development of drug resistance have limited their use. The newer antivirals zanamivir and oseltamivir are equally effective and have the advantage of being well tolerated and active against both influenza A and B without the development of resistance. However, they are costly. Early identification and diagnosis of influenza illnesses are crucial since treatment with antiviral agents should be started within 48 hours of the beginning of illness.     

Antiviral drugs in influenza: an adjunct to vaccination in some situations

(1) Influenza is a common acute respiratory disease due to a virus that causes annual seasonal epidemics. Three major pandemics occurred in the 20th century, in 1918-1919, 1957 and 1968, mainly due to genetic variants of type A influenza virus. (2) In temperate regions the incidence of hospitalisation increases during annual influenza epidemics. More than 90% of deaths linked to influenza involve people over 65 years of age. (3) The clinical manifestations of influenza virus infection are non specific. The main complications are secondary bacterial respiratory tract infections (especially pneumonia); those most at risk are people over 65, infants less than one year old, and people with underlying chronic disorders (pulmonary, cardiac, renal or metabolic) or immune deficiencies. (4) Vaccination is the main preventive measure. During most years the vaccine strain closely matches the epidemic strain. In relative terms, vaccination of people over 65 reduces the number of deaths linked to influenza by about 80%, hospitalisation and pneumonia by about 50%, and symptomatic influenza by about 30%. Yearly vaccination is recommended for younger people with serious chronic disease. (5) Three antiviral drugs are currently approved in France for prevention or treatment of influenza: amantadine and the neuraminidase inhibitors zanamivir and oseltamivir. (6) Efficacy of antiviral drugs has not been evaluated in comparative randomised trials in which death and influenza complications were the primary outcome measures. (7) A systematic review of 20 comparative randomised trials involving about 2500 healthy people showed that amantadine reduced the frequency of flu-like syndromes by about 7% in absolute terms (26.3% versus 33.1% with placebo). Zanamivir and oseltamivir have only been shown to reduce the frequency of serologically confirmed episodes of influenza (0.4% to 2.5%, compared to 4.4% to 14.9% with placebo). (8) In a randomised placebo-controlled trial of oseltamivir, involving 548 institutionalised subjects over 65 years of age, more than 80% of whom had been vaccinated, respiratory tract infections were less frequent in the oseltamivir group, but the relevance of this result is undermined by the small number of observed cases. (9) Efficacy of antiviral drugs on avian influenza (bird flu) was studied during a 2003 Dutch outbreak due to a type A/H7N7 virus. Among the 38 exposed persons who were treated, about 3% developed symptoms, compared with about 10% of 52 exposed persons who refused treatment (p = 0.38). The low statistical power and the lack of randomisation rule out any firm conclusions on preventive effects. (10) The three antiviral drugs have different profiles of adverse effects and drug interactions. Amantadine carries a risk of neuropsychological, atropinic and dopaminergic adverse effects, and can interact with drugs that have similar effects. Zanamivir carries a risk of life-threatening bronchospasm. Oseltamivir was approved relatively recently and its full spectrum of adverse effects is not yet known; its main adverse effects appear to be mild gastrointestinal disturbances, although a few cases of serious cutaneous reactions have been reported. (11) In vitro resistance to the three drugs has been demonstrated, but the possible clinical and epidemiological consequences are unclear. (12) In situations warranting antiviral therapy for the prevention of influenza, oseltamivir, at a dose of 75 mg/day for 10 days, is the drug with the best risk-benefit balance. Its use should be limited to situations where a major potential benefit exists in order to avoid selection for resistant strains. (13) Testing of oseltamivir in children is limited. Oseltamivir should be avoided during pregnancy, because of evidence that it may harm the unborn child. (14) In practice, the use of antiviral drugs in otherwise healthy adults and children is not generally recommended. (15) Despite the lack of convincing data regarding the efficacy of oseltamivir in preventing complications of influenza, its effect on documented infections suggests it may be useful for unvaccinated individuals who are at high risk of infection and severe complications. Under these conditions, treatment should be started within 48 hours after contact with a person who has flu-like symptoms during a seasonal epidemic; residents in institutions in which influenza cases occur may also qualify for preventive treatment. Other preventive measures should also be used, including immediate vaccination, case isolation, use of face masks, and more frequent hand washing. (16) During seasonal influenza epidemics due to viral strains against which the current vaccine is of limited effectiveness, the utility, target populations and optimal duration of preventive antiviral treatment must be determined by examining the groups most at risk and the severity of complications. (17) Most flu-like syndromes are not due to the influenza virus, and the preventive effect of antiviral drugs on complications in persons at risk has not yet been demonstrated. (18) In practice, antiviral drugs are not an alternative to influenza vaccination, but may be a useful adjunct in some situations. It is best to limit their use to short-term prophylaxis of vulnerable persons in situations where the risk of contracting influenza virus infection is high.     

Antiviral therapy for influenza : a clinical and economic comparative review

Each year influenza epidemics cause a considerable burden of disease. Vaccination against influenza A and B viruses has been and remains the cornerstone of influenza prevention, but antiviral therapy can serve as an important adjunct to vaccination in controlling the impact of the disease. Two classes of drugs are currently licensed in a large number of countries for the treatment of influenza. The M2 ion channel blockers or amantadanes (amantadine and rimantadine) are specific inhibitors of influenza A virus replication, whereas the neuraminidase inhibitors (zanamivir and oseltamivir) are active against influenza A and B viruses. Readily transmissible drug-resistant viruses develop frequently during amantadane treatment but not during neuraminidase inhibitor treatment. In this review, efficacy and safety data from randomised controlled trials are evaluated to gain an understanding of what we can and cannot expect from antiviral treatment. All four drugs shorten the course of influenza disease by approximately 1 day and relieve symptoms to some extent, but there is still uncertainty as to whether antiviral therapy leads to a reduction of serious complications and hospitalisation. The results of cost-effectiveness analyses are very diverse, in part because of differences in methodology but also because there is no consensus on what probabilities to assign to the key risks and benefits that form the basis of these studies. Consensus statements by advisory bodies in England and Germany recommend neuraminidase inhibitors for the therapy of influenza in high-risk individuals such as people over 65 years or under 2 years, and individuals with chronic cardiovascular, pulmonary or renal disease, diabetes mellitus or immunosuppression. However, there is no agreement as to whether antiviral therapy can be generally recommended for otherwise healthy children and adults. The availability of safe and effective antiviral therapy options should be kept in mind by the practising clinician, while more specific recommendations and policy formulation will depend on additional efficacy data that include frequency of complications and hospitalisation as outcome measures.     

流感病毒血凝素在多种系统中表达的研究进展

流感疫苗是预防流感病毒感染最有效的方法。传统灭活流感疫苗通过在鸡胚中培养病毒后经纯化获得。流感每年都会发生季节性流行,流感病毒高度多变的特性使生产有效疫苗成为一项挑战。为了克服流感疫苗生产对鸡胚的依赖,需要开发新的流感疫苗生产策略。由于血凝素是流感病毒主要表面抗原之一,重组血凝素亚单位疫苗为流感疫苗的生产提供了一个方案。本文将对流感病毒血凝素在大肠埃希菌、毕赤酵母、昆虫细胞、哺乳动物细胞多种系统中表达的研究进行综述。     

Development of Stable Influenza Vaccine Powder Formulations: Challenges and Possibilities

Influenza vaccination represents the cornerstone of influenza prevention. However, today all influenza vaccines are formulated as liquids that are unstable at ambient temperatures and have to be stored and distributed under refrigeration. In order to stabilize influenza vaccines, they can be brought into the dry state using suitable excipients, stabilizers and drying processes. The resulting stable influenza vaccine powder is independent of cold-chain facilities. This can be attractive for the integration of the vaccine logistics with general drug distribution in Western as well as developing countries. In addition, a stockpile of stable vaccine formulations of potential vaccines against pandemic viruses can provide an immediate availability and simple distribution of vaccine in a pandemic outbreak. Finally, in the development of new needle-free dosage forms, dry and stable influenza vaccine powder formulations can facilitate new or improved targeting strategies for the vaccine compound. This review represents the current status of dry stable inactivated influenza vaccine development. Attention is given to the different influenza vaccine types (i.e. whole inactivated virus, split, subunit or virosomal vaccine), the rationale and need for stabilized influenza vaccines, drying methods by which influenza vaccines can be stabilized (i.e. lyophilization, spray drying, spray-freeze drying, vacuum drying or supercritical fluid drying), the current status of dry influenza vaccine development and the challenges for ultimate market introduction of a stable and effective dry-powder influenza vaccine.     

M2 protein-a proton channel of influenza A virus

Recent outbreaks of highly pathogenic avian influenza A virus infections (H5 and H7 subtypes) in poultry and humans have raised concerns that a new influenza pandemic will occur in near future. Currently, four antivirals have proven efficacy in the treatment and prophylaxis of influenza A infections: two M2 inhibitors (amantadine and rimantadine) and two neuraminidase inhibitors (zanamivir and oseltamivir). Early treatment with antivirals reduces the duration of symptoms and the time to recovery by one to two days. However, when antivirals are used for the treatment the antiviral resistance develops rapidly, limiting their use. There is an urgent need for research on newer antiviral agents and "universal" vaccine against influenza virus. The M2 protein from the influenza A virus forms a proton channel in the virion and is essential for infection. As a relatively conserved protein, the M2 protein seems to be a suitable candidate for development of a new generation of vaccine or antiviral agents. This review describes the role of the M2 ion channel in virus replication and the structure-function relationship of the channel.     

Clinical use of antiviral drugs

Remarkable progress has been made in antiviral chemotherapy. Six approved antiviral drugs are now available for the treatment of various viral infections. Trifluridine, idoxuridine and vidarabine are all effective in patients with herpes keratitis; trifluridine is preferred due to its low toxicity. Acyclovir is the drug of choice in patients with infections due to herpes simplex viruses, including genital herpes, herpes encephalitis, and neonatal herpes, and infections due to varicella-zoster virus. Amantadine is the only drug currently available for prophylaxis and treatment of influenza A, but an investigational drug, rimantadine, appears to be equally effective and less toxic than amantadine. Ribavirin is the most recently approved antiviral agent for the treatment of respiratory syncytial virus infections. Numerous antiviral drugs are being studied in patients with acquired immunodeficiency syndrome. Although currently available drugs have improved our ability to manage a variety of viral illnesses, much needs to be learned about specific dosage guidelines based on the studies of pharmacokinetics, pharmacodynamics, potential adverse effects and viral resistance, and the role of combination therapy to optimize therapy.     

Influenza

The currently available antiviral drugs rimantadine and amantadine are effective only for influenza A viruses. Another class of influenza antiviral drugs is the neuraminidase inhibitors, which selectively inhibit both influenza A and B viruses. Recent studies have found the neuraminidase inhibitors zanamivir and oseltamivir to be 67 - 82% effective in preventing laboratory-confirmed infection when administered as prophylaxis during the influenza season. As treatment, they reduce the duration of illness by 1 - 1.5 days when started within 36 - 48 h of illness onset. The reported adverse effects of these drugs are minimal, and unlike amantadine and rimantadine, the drugs do not appear to affect the central nervous system. Poor oral bioavailability and rapid renal clearance limit the use of zanamivir to inhalation and concern has been raised about its use in asthmatics. The sialic acid analogue, GS4071, has been shown to be a potent inhibitor of neuraminidase activity and is shown to be effective in controlling influenza, and its prodrug form - GS4104 (oseltamivir) can be given orally. Direct comparison of zanamivir and oseltamivir, their use for prophylaxis and treatment in high-risk groups, and evaluation of their cost effectiveness are all required before they enter routine clinical practice.     

Influenza

The currently available antiviral drugs rimantadine and amantadine are effective only for influenza A viruses. Another class of influenza antiviral drugs is the neuraminidase inhibitors, which selectively inhibit both influenza A and B viruses. Recent studies have found the neuraminidase inhibitors zanamivir and oseltamivir to be 67-82% effective in preventing laboratory-confirmed infection when administered as prophylaxis during the influenza season. As treatment, they reduce the duration of illness by 1-1.5 days when started within 36-48 h of illness onset. The reported adverse effects of these drugs are minimal, and unlike amantadine and rimantadine, the drugs do not appear to affect the central nervous system. Poor oral bioavailability and rapid renal clearance limit the use of zanamivir to inhalation and concern has been raised about its use in asthmatics. The sialic acid analogue, GS4071, has been shown to be a potent inhibitor of neuraminidase activity and is shown to be effective in controlling influenza, and its prodrug form--GS4104 (oseltamivir) can be given orally. Direct comparison of zanamivir and oseltamivir, their use for prophylaxis and treatment in high-risk groups, and evaluation of their cost effectiveness are all required before they enter routine clinical practice.     

Oseltamivir: new indication. Prevention of influenza in at-risk children: vaccination is best

(1) Complications of influenza are rare in children and mainly affect children with serious birth defects or chronic underlying disorders such as cystic fibrosis and severe asthma. (2) Oseltamivir is the second antiviral drug, after amantadine, to be marketed in the European Union for the prevention of influenza in children aged from 1 to 12 years. (3) The clinical evaluation of oseltamivir in this indication is limited to a retrospective subgroup analysis of an unblinded trial versus no treatment. The data suggest that oseltamivir is at best only modestly effective in reducing the incidence of laboratory-confirmed influenza (about 7% versus 19%). With zanamivir, the incidence of laboratory-confirmed influenza was about 2%, versus 6% to 15% in the placebo groups in several trials. As of 5 January 2007, zanamivir had not been marketed for paediatric use in France. With amantadine, the incidence was about 3% to 9%, depending on the trial, versus 9% to 30% on placebo. Amantadine has only been shown to have an effect on type A influenza virus and is only available in tablet form (unsuitable for young children). In summary, there is no firm evidence that antiviral prophylaxis reduces the rate of influenza complications in children. (4) Severe cutaneous and neurological adverse effects have been reported in children treated with oseltamivir. Pharmacovigilance studies show a risk of angioedema and toxic epidermal lysis with oseltamivir. (5) There are worrisome reports of influenza virus strains resistant to available antivirals. (6) In practice, oseltamivir is not sufficiently effective or safe for the prevention of influenza in children, which does not justify its use other than in clinical trials.     

Influenza vaccination and antiviral therapy: is there a role for concurrent administration in the institutionalised elderly?

Influenza vaccination is estimated to be 50-68% efficacious in preventing pneumonia, hospitalisation or death in nursing home residents. Large culture-proven outbreaks may occur despite high resident vaccination rates. There is, therefore, a significant role for concurrent administration of influenza vaccination and antiviral therapy. The use of antiviral treatment and chemoprophylaxis requires community reporting of viral isolates, and contingency plans for rapid case identification and application of antiviral therapy. Clinicians must react quickly to control a highly infectious seasonal pathogen that may strike as an explosive outbreak. This situation is unique in geriatric practice. Current antiviral treatment should be administered within 48 hours of symptom onset, and is more efficacious if administered within 12 hours. In the case of an explosive institutional outbreak, a 1-day delay in prophylaxis may allow infection of many residents with a potentially fatal illness. Influenza must be differentiated from other respiratory viruses or syndromes. Grouped rapid diagnostic tests can aid laboratory confirmation. Antiviral agents include the M(2) inhibitors, amantadine and rimantadine, active against influenza A, and the neuraminidase inhibitors, zanamivir and oseltamivir, active against influenza A and B. In our experience, influenza B illness is as severe as influenza A. All agents have similar efficacy as treatment and prophylaxis against sensitive strains. When M(2) inhibitors are used simultaneously within an enclosed space (i.e. household or nursing home) as both treatment and prophylaxis, resistant strains may emerge that limit prophylactic efficacy. When M(2) inhibitors are administered to suspected cases (residents or staff) in institutions, precautions against secretion are especially important to diminish the risk of transmission of resistant virus. Rimantadine has been shown to have significantly fewer CNS adverse events compared with amantadine. Amantadine and oseltamivir require dosage adjustment in those with renal impairment. Oseltamivir, rimantadine and amantadine are administered by mouth, while zanamivir is administered by oral inhalation in a lactose powder. The labelling advises caution in the use of zanamivir in those with underlying airway disease. Pooled analysis of studies in patients given zanamivir indicate that individuals over the age of 50 years (at high risk for complications) and those severely symptomatic at presentation, tend to benefit most from early treatment. Neuraminidase inhibitors also diminish the need for antibacterials to treat secondary complications. An institutional programme to control influenza should include vaccination, and contingency plans for clinical surveillance, specimen processing and the rapid application of antiviral treatment and prophylaxis.     

Epidemiology, prevention, and management of influenza in patients with hematologic malignancy

Influenza results in annual epidemics of respiratory viral illness during the winter; when a novel virus enters the human population, a pandemic may result with a larger proportion of the population sickened. Unlike the mild and typically self-limited disease seen in immunocompetent patients, immunocompromised patients frequently have a more severe course. These individuals shed virus for a prolonged period of time, have a high rate of viral pneumonia, more frequently develop bacterial and fungal super-infections, and may develop late-onset airflow obstruction. Further, antiviral resistance develops more frequently in immunosuppressed patients. Although the cornerstone of prevention of influenza is vaccination, vaccine efficacy in patients with hematologic malignancies, particularly stem cell transplant recipients, is poor. Alternative preventative measures, such as seasonal antiviral prophylaxis can be considered. Lastly, there have been no prospective studies of antivirals in the management of influenza infections in these patients. As such, the optimal regimen and duration remains to be defined. Available evidence suggests that prolonged course are frequently needed. Patients who fail to response or have relapsed infections should be tested for emergence of antiviral resistance and alternative diagnoses should be investigated.     

Optimized development of a candidate strain of inactivated EV71 vaccine and analysis of its immunogenicity in rhesus monkeys

Enterovirus type 71 (EV71) is one of the main etiologic agents responsible for periodic epidemics of hand-foot-and-mouth disease (HFMD). The prevention and control of EV71 epidemics with effective anti-viral agents and vaccines is very important for public health. Because the pathogenesis of EV71 in the human body is not completely clear and genetic variations in the virus during its replication are difficult to control, we have focused on the development of an inactivated whole-virus vaccine. In this study, we screened 16 strains isolated from different areas of China and selected one strain for the development of an inactivated EV71 vaccine. The results of our study suggest that the FY-23K-B strain, which is a candidate strain for an EV71 inactivated vaccine, satisfied the requirements of vaccine production in terms of genetic stability, biological activity, and good immunogenicity. The experimentally inactivated vaccine produced using this strain was capable of inducing an immune response and offered protection to rhesus monkeys against future virus attacks.     

Intranasal cold-adapted influenza virus vaccine combined with inactivated influenza virus vaccines: an extra boost for the elderly?

Although influenza vaccine delivery strategies have improved coverage rates to unprecedented levels nationally among persons aged 65 years and older, influenza remains one of the greatest vaccine-preventable threats to public health among elderly in the US. A new, intranasal live attenuated influenza vaccine (LAIV) was recently approved by the US FDA for use in persons aged 5-49 years, which excludes the elderly population. Limitations of immune response to inactivated influenza vaccine (IAIV) and effectiveness of current influenza vaccination strategies among the elderly suggest that a combined approach using LAIV and/or the IAIV in various permutations might benefit this group. We explore characteristics of the LAIV, data regarding its utility in protecting against influenza in the elderly, and challenges and opportunities regarding potential combined inactivated/live attenuated vaccination strategies for the elderly. Although LAIV appears to hold promise either alone or in combination with IAIV, large well conducted randomised trials are necessary to define further the role of LAIV in preventing influenza morbidity and mortality among the elderly. We also suggest that innovative vaccine coverage strategies designed to optimise prevention and control of influenza and minimise viral transmission in the community must accompany, in parallel, the acquisition of clinical trials data to best combat morbidity and mortality from influenza.     

Neuraminidase inhibitors for the treatment and prevention of influenza

The impact of influenza virus infection is estimated to run into billions of dollars worldwide. Vaccination plays a key role in prevention; however, vaccines do not provide complete protection against influenza due to the constant mutation of the virus responsible. Unlike amantadine and rimantadine, which are only effective against influenza A, the new neuraminidase inhibitors zanamivir (Relenza), GlaxoSmithKline) and oseltamivir (Tamiflu), Gilead/Roche) are potent and specific inhibitors of influenza types A and B and have minimal side effects. The greatest benefit is derived if treatment commences as soon as possible after symptoms develop. In order for these inhibitors to have a significant impact on the disease, clinicians and the general public need to be made more aware of the symptoms of influenza and the availability of these new drugs.     

Development of antivirals against influenza

Morbidity and mortality due to influenza virus infections remain a major problem throughout the world. Yearly, medical costs and loss of productivity resulting from influenza infection are estimated to be in the range of 12 dollars bn in the USA. The predicted increases in the elderly and immune-deficient populations will make influenza an even greater threat in the future. Despite the availability of vaccines, they have been least effective in these high-risk populations. Coupled with the requirement for routine revaccination, the need for effective antiviral agents is illustrated. The currently approved drugs, amantadine, rimantadine and ribavirin (in some countries), have limitations. They are only inhibitory against influenza A viruses, are prone to adverse reactions and quickly give rise to resistant virus. This review examines current drug therapies, antivirals in development and possible future opportunities for anti-influenza drugs.     

Neuraminidase inhibitors for the treatment and prevention of influenza

The impact of influenza virus infection is estimated to run into billions of dollars worldwide. Vaccination plays a key role in prevention; however, vaccines do not provide complete protection against influenza due to the constant mutation of the virus responsible. Unlike amantadine and rimantadine, which are only effective against influenza A, the new neuraminidase inhibitors zanamivir (Relenza^®, GlaxoSmithKline) and oseltamivir (Tamiflu^®, Gilead/Roche) are potent and specific inhibitors of influenza types A and B and have minimal side effects. The greatest benefit is derived if treatment commences as soon as possible after symptoms develop. In order for these inhibitors to have a significant impact on the disease, clinicians and the general public need to be made more aware of the symptoms of influenza and the availability of these new drugs.