MicrobiologyBytes

Chronic hepatitis B virus (HBV) infection affects about 400 million people around the globe, being one of the most common infectious diseases and among the world’s leading causes of death. Antiviral therapy of chronic hepatitis B (CHB) aims to improve quality of life and survival chance of the patients by preventing progression of liver damage to cirrhosis, end-stage liver disease and liver cancer (HCC), thus preventing anticipated liver-related death. This goal is achieved by suppression of HBV replication in a sustained or maintained manner, either by short-term “curative” treatment with standard (IFN) and pegylated interferon (Peg-IFN) or long-term “suppressive” therapy with nucleos(t)ide analogues, like lamivudine, adefovir, entecavir, telbivudine and tenofovir. Since both strategies have advantages and disadvantages, the wise treatment of a patient with CHB requires careful balance between prediction of the natural history of HBV and of the potential benefit of anti- HBV therapy. Recent data on the long-term efficacy of third generation of nucleos(t)ide analogues entecavir and tenofovir have tipped the balance towards long-term suppression therapy as the first-line option for most patients with CHB, independent of the HBeAg status.

Chronic hepatitis C is a major worldwide health problem with an estimated prevalence of 1.6-2%. In Europe, more than 9 million chronic carriers and approximately 86,000 deaths per year are estimated due to the late complications of hepatitis C virus (HCV). The prognosis of chronic hepatitis C depends on the rate of fibrosis progression, which over a 20-30 year time span, may determine the risk of developing cirrhosis and its complications, namely HCC, liver decompensation, hepatic encephalopathy and oesophageal variceal bleeding. The only therapeutic intervention able to halt this progressive process is eradication of HCV by Interferon (IFN)-based therapies. Since the empirical choice to use IFN in 1986, therapy for chronic hepatitis C has constantly evolved over the past decade, with the attainable sustained virological response (SVR) rates increasing through the years. The addition of the guanosine nucleoside analogue ribavirin (Rbv) to IFN can be considered the major breakthrough in the treatment of chronic hepatitis C. Through mechanisms of action that still remain largely unknown, Rbv has determined a greater number of patients to ultimately achieve a SVR by increasing the rates of on-treatment response and reducing the rates of post-treatment relapse. In the large phase III clinical trials designed to assess its efficacy and safety, the combination of IFN and Rbv resulted in SVR rates of 30-35% in HCV genotype 1 patients and 75-80% in HCV-2 and 3 patients. These figures exceeded by far those obtained by IFN monotherapy, effectively leading the way for combination therapy to become the standard of care in the late 1990’s. The latest innovation in the treatment of chronic hepatitis C has been the pegylation of the IFN molecule (PegIFN) through the attachment of one or more polyethylene glycols to the IFN, a process that is able to modify the immunological, pharmacokinetic and pharmacodynamic properties of the drug. Standard IFN was in fact characterized by a number of limitations, such as poor stability, short elimination half-life and potential immunogenicity, that ultimately determined its small antiviral effect. Moreover, due to the increase in elimination half-life obtained by the pegylation process, it has been possible to lengthen the dosing interval from the unpractical three times a week schedule required by standard IFN, to the more “user friendly” once a week administration, a feature that has increased convenience whilst facilitating adherence to the recommended treatment schedule. Following the demonstration of a more potent antiviral effect in terms of SVR rates in phase III randomized trials, PegIFN has become the standard of care for chronic hepatitis C.

One year of interferon therapy inhibits HBV replication in one third of the patients whereas long-term administration of oral nucleos(t)ide analogues is efficient in most of them, as long as early treatment adaptation in patients with partial virological response and resistance is provided. Following the demonstration of a more potent antiviral effect in terms of sustained virological response (SVR) rates, Pegylated-IFN coupled with Ribavirin has become the standard treatment for chronic hepatitis C, with nearly 65% of all treated patients achieving a SVR. Long-term suppression of HBV and eradication of HCV would halt the progression of chronic hepatitis to cirrhosis, hepatocellular carcinoma and liver decompensation.

HBV and HCV Therapy. Viruses 2009, 1(3), 484-509. doi:10.3390/v1030484

Related:

• Hepatitis B and C viruses
• Hepatitis C Virus: a mountain to climb
• Does the outcome of HCV infection vary with the infecting virus type?
• Plugging the holes in hepatitis C virus antiviral therapy

The best ways of managing patients with influenza H5N1 infection are debated by experts in this week’s PLoS Medicine (What Is the Optimal Therapy for Patients with H5N1 Influenza? PLoS Med 6(6): e1000091 doi:10.1371/journal.pmed.1000091). In 2007 the World Health Organization described a new process for rapidly developing clinical management guidelines in emergency situations. This guideline recommends giving the antiviral drug oseltamivir (Tamiflu) at a dose of 75 mg twice daily for five days. Doses higher than this recommended amount should be used to fight H5N1 influenza, argues Nicholas White.  In contrast to the current WHO guidelines, he argues that higher doses should be given for H5N1 infection to avoid any possibility of under-dosing those patients with unusual pharmacokinetics and more resistant organisms. This will come at the expense of increased toxicity, he says, but is necessary given the mortality burden of H5N1 infection and the fact that H5N1 replicates more rapidly than seasonal influenza viruses, reaches much greater viral burdens than do other human influenza viruses, and resistance develops swiftly.

Robert Webster and Elena Govorkova disagree. They argue that we must instead consider a multidrug approach to managing patients with H5N1, an approach that is supported by animal data and “can guard against the emergence of resistant strains.”  Tim Uyeki from the Centers for Disease Control and Prevention in Atlanta, USA, emphasizes theneed for more data to help inform clinical management of patients with H5N1 infections. In the absence of these data, he argues, we need a multipronged strategy: pharmacological strategies including combination antiviral treatment, anti-inflammatory agents, and immunotherapy, and non-pharmacological strategies such as the standardization of optimal ventilator and fluid management, especially for acute respiratory distress syndrome, and management of other complications.

Related:

• MicrobiologyBytes: H5N1 | Influenza | Oseltamivir

Assessing the quality of information on the internet is all about filtering – whether it’s a blog post or a peer-reviewed journal. I don’t want to shock you, but not everything published in peer-reviewed journals is correct, you still need to use your judgement. And some blogs provide some of the best information out there. The best example of this I’ve come across recently is How do adamantane drugs block M2? by Michael Clarkson:

Vaccination plays such an important role in our seasonal influenza strategy in part because we don’t have many medicines that can be brought to bear on the disease. The neuraminidase inhibitors (specifically Tamiflu) are widely stockpiled, and continue to work for now, but the specter of resistance is already lurking. If these drugs are too widely or too improperly used, there is a good chance that resistance mutations will eventually render these drugs ineffective. Universal drug resistance may already be the fate of the drugs amantadine and rimantadine, built on an adamantane backbone. The adamantane drugs inhibit the M2 proton channel from influenza A, a tiny tetrameric protein that equalizes pH between the virus and the endosome of the cell that has swallowed it. This process releases the virus contents so that they can do their damage to the cell, so these medicines can significantly retard the infection process. Or rather, they could, if so many influenza strains didn’t harbor the S31N mutation that almost completely nullifies their effect. If we are to develop new drugs to attack the M2 channel, it would be helpful to know how this mutation causes drug resistance. Over the past few years a great deal of structural evidence has accumulated showing how adamantane drugs work on the older, non-resistant channels. The problem is that the evidence supports two different models of M2 inhibition, and so far it has proven difficult to determine which of them is probably correct…

read more…

Related:

• The Biology of Influenza
• Antiviral Drugs
• Viroporins

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Related:

• 10 things you should know about H1N1 (swineflu)
• 10 more things you should know about H1N1 (swineflu)

A paper published in this week’s issue of PLoS Biology describes a study that has reactivated a dormant gene found in humans and coaxed it – in tissue culture – to produce an antiviral peptide. Lead scientist Alexander Cole used aminoglycosides – drugs commonly used to fight bacterial infections – to trigger the production of the protein, which is encoded by the dormant human defensin gene that he calls “retrocyclin”. The authors hope that this research might ultimately lead to the development of a treatment that would activate the gene in a person’s own cells, for example, and thereby prevent infection with viruses in the treated tissue.

Defensins are a large family of small antimicrobial peptides that contribute to host defense against a broad spectrum of pathogens. In primates, defensins are divided into three subfamilies – alpha, beta, and theta – on the basis of their disulfide bonding pattern. Theta-defensins were the most recently identified defensin subfamily, isolated initially from white blood cells and bone marrow of rhesus monkeys. They are the only known cyclic peptides in mammals and act primarily by preventing viruses such as HIV-1 from entering cells. Whereas theta-defensin genes are intact in Old World monkeys, in humans they have a premature stop codon that prevents their expression; they thus exist as pseudogenes. On correction of the premature termination codon in theta-defensin pseudogenes, human myeloid cells produce cyclic, antiviral peptides, indicating that the cells retain the intact machinery to make cyclic peptides. Given that the endogenous production of retrocyclins could also be restored in human tissues, the possibility exists that that aminoglycoside-based topical microbicides might be useful in preventing sexual transmission of HIV-1.

Dozens of scientists around the world are looking for ways to prevent the transmission of viruses such as HIV. Cole and colleagues have previously discovered that retrocyclin proteins found in some primates appeared to prevent HIV infections in cell cultures. The same gene exists in humans, but because of a mutation that interrupts the gene sequence, it no longer produces protein. Now, a collaboration between researchers has found that restoring the production of retrocyclins prevents HIV entry into human cells. The scientists have found a way to get the gene to produce the retrocyclin and then showed that the retrocyclin appears to prevent the transmission of HIV in cells cultured in the laboratory. They applied aminoglycoside antibiotics to vaginal tissues and cervical cells in the lab and found the antibiotic appears to stimulate those cells and tissues to produce retrocyclins on their own. There is a possibility the aminoglycoside antibiotics will be used in a cream or gel format that could someday be a simple way to prevent the transmission of HIV. Much more work would be required before this would be possible, including taking the result in tissue culture and showing the same effect in whole organisms.

Reawakening retrocyclins: ancestral human defensins active against HIV-1. 2009 PLoS Biol 7(4):e1000095
Human alpha and beta defensins contribute substantially to innate immune defenses against microbial and viral infections. Certain nonhuman primates also produce theta-defensins—18 residue cyclic peptides that act as HIV-1 entry inhibitors. Multiple human theta-defensin genes exist, but they harbor a premature termination codon that blocks translation. Consequently, the theta-defensins (retrocyclins) encoded within the human genome are not expressed as peptides. In vivo production of theta-defensins in rhesus macaques involves the post-translational ligation of two nonapeptides, each derived from a 12-residue ‘‘demidefensin’’ precursor. Neither the mechanism of this unique process nor its existence in human cells is known. To ascertain if human cells retained the ability to process demidefensins, we transfected human promyelocytic cells with plasmids containing repaired retrocyclin-like genes. The expected peptides were isolated, their sequences were verified by mass spectrometric analyses, and their anti-HIV-1 activity was confirmed in vitro. Our study reveals for the first time, to our knowledge, that human cells have the ability to make cyclic theta-defensins. Given this evidence that human cells could make theta-defensins, we attempted to restore endogenous expression of retrocyclin peptides. Since human theta-defensin genes are transcribed, we used aminoglycosides to read-through the premature termination codon found in the mRNA transcripts. This treatment induced the production of intact, bioactive retrocyclin-1 peptide by human epithelial cells and cervicovaginal tissues. The ability to reawaken retrocyclin genes from their 7 million years of slumber using aminoglycosides could provide a novel way to secure enhanced resistance to HIV-1 infection.

Related:

• MicrobiologyBytes: HIV/AIDS

Acquired immunodeficiency syndrome (AIDS) has killed more than 25 million people since 1981 and more than 30 million people (22 million in sub-Saharan Africa alone) are now infected with the human immunodeficiency virus (HIV), which causes AIDS. HIV destroys immune system cells (including CD4 cells, a type of lymphocyte), leaving infected individuals susceptible to other infections. Early in the AIDS epidemic, most HIV-positive people died within ten years of infection. Then, in 1996, highly active antiretroviral therapy (ART) – combinations of powerful antiretroviral drugs – was developed and the life expectancy of HIV-infected people living in affluent countries improved dramatically. Now, in industrialized countries, all-cause mortality (death from any cause) among HIV-infected patients treated successfully with ART is similar to that of the general population and the mortality rate (the number of deaths in a population per year) among patients with HIV/ AIDS is comparable to that among patients with diabetes and other chronic conditions.

Unfortunately, combination ART is costly, so although HIV/AIDS quickly became a chronic disease in industrialized countries, AIDS deaths continued unabated among the millions of HIV-infected people living in low- and middle-income countries. Then, in 2003, governments, international agencies and funding bodies began to implement plans to increase ART coverage in developing countries. By the end of 2007, nearly three million people living with HIV/AIDS in these countries were receiving ART – nearly a third of the people who urgently need ART. In sub-Saharan Africa more than 2 million people now receive ART and mortality in HIV-infected patients who have access to ART is declining. However, no-one knows how mortality among HIV-infected people starting ART compares with non-HIV related mortality in sub-Saharan Africa. This information is needed to ensure that appropriate health services (including access to ART) are provided in this region. In a new study, researchers compared mortality rates among HIV-infected patients starting ART with non-HIV related mortality in the general population of four sub-Saharan countries.

The researchers obtained estimates of the number of HIV-unrelated deaths and information about patients during their first two years on ART at five antiretroviral treatment programs in the Cote d’Ivoire, Malawi, South Africa, and Zimbabwe from the World Health Organization Global Burden of Disease project and the International epidemiological Databases to Evaluate AIDS initiative. They then calculated the excess mortality rates among the HIV-infected patients (the death rates in HIV-infected patients minus the national HIV-unrelated death rates) and the standardized mortality rate (SMR; the number of deaths among HIV-infected patients divided by the number of HIV-unrelated deaths in the general population). The excess mortality rate among HIV-infected people who started ART when they had a low CD4 cell count and clinically advanced disease was 17.5 per 100 person-years of follow-up. For HIV-infected people who started ART with a high CD4 cell count and early disease, the excess mortality rate was 1.0 per 100 person-years. The SMRs over two years of ART for these two groups of HIV-infected patients were 47.1 and 3.4, respectively. Finally, patients who started ART with a high CD4 cell count and early disease who survived the first year of ART had an excess mortality of only 0.27 per 100 person-years and an SMR over two years followup of only 1.14.

These findings indicate that mortality among HIV-infected people during the first two years of ART is higher than in the general population in these four sub-Saharan countries. However, for patients who start ART when they have a high CD4 count and clinically early disease, the excess mortality is moderate and similar to that associated with diabetes. Because the researchers compared the death rates among HIV-infected patients with estimates of national death rates rather than with estimates of death rates for the areas where the ART programs were located, these findings may not be completely accurate. Nevertheless, these findings support further expansion of strategies that increase access to ART in sub-Saharan Africa and suggest the excess mortality among HIV-infected patients in this region might be largely prevented by starting ART before an individual’s HIV infection has progressed to advanced stages.

Mortality of HIV-Infected Patients Starting Antiretroviral Therapy in Sub-Saharan Africa: Comparison with HIV-Unrelated Mortality. 2009 PLoS Med 6(4): e1000066

Mortality in HIV-infected patients who have access to highly active antiretroviral therapy (ART) has declined in sub-Saharan Africa, but it is unclear how mortality compares to the non-HIV–infected population. We compared mortality rates observed in HIV-1–infected patients starting ART with non-HIV–related background mortality in four countries in sub- Saharan Africa. Patients enrolled in antiretroviral treatment programmes in Cote d’Ivoire, Malawi, South Africa, and Zimbabwe were included. We calculated excess mortality rates and standardised mortality ratios (SMRs) with 95% confidence intervals (CIs). Expected numbers of deaths were obtained using estimates of age-, sex-, and country-specific, HIV-unrelated, mortality rates from the Global Burden of Disease project. Among 13,249 eligible patients 1,177 deaths were recorded during 14,695 person-years of follow-up. The median age was 34 y, 8,831 (67%) patients were female, and 10,811 of 12,720 patients (85%) with information on clinical stage had advanced disease when starting ART. The excess mortality rate was 17.5 (95% CI 14.5–21.1) per 100 person-years SMR in patients who started ART with a CD4 cell count of less than 25 cells/ml and World Health Organization (WHO) stage III/IV, compared to 1.00 (0.55–1.81) per 100 person-years in patients who started with 200 cells/ml or above with WHO stage I/II. The corresponding SMRs were 47.1 (39.1–56.6) and 3.44 (1.91– 6.17). Among patients who started ART with 200 cells/ml or above in WHO stage I/II and survived the first year of ART, the excess mortality rate was 0.27 (0.08–0.94) per 100 person-years and the SMR was 1.14 (0.47–2.77). Mortality of HIV-infected patients treated with combination ART in sub-Saharan Africa continues to be higher than in the general population, but for some patients excess mortality is moderate and reaches that of the general population in the second year of ART. Much of the excess mortality might be prevented by timely initiation of ART.

Related:

• HIV treatment in Africa as successful as in Europe, if started in time
• HIV gene therapy trial promising
• HIV “can never be cured”
• Retroviruses
• HIV mutation and the immune response
• Immune exhaustion in HIV infection
• How does HIV cause AIDS?

Latest News (unfiltered) | Latest news (filtered) (via Twitter)

1. What is swine flu?
Swine flu is a type of influenza virus. Influenza viruses are named after the proteins on the outside which are recognized by the body, H and N. There are dozens of combinations of these two proteins, each one giving a different type of influenza virus. Swine flu virus is H1N1 influenza. The original swine flu virus was first isolated from a pig in 1930.

2. Can it hurt me?
Influenza viruses infect pigs (swine), birds, humans and a few other species. Most strains of influenza are quite restricted in the host they will infect but occasionally jump from one species to another. Swine flu infects pigs but is also capable of infecting humans.

3. Will there be a swine flu pandemic?
It’s too early to say. Scientists are carefully recording the spread of the current epidemic to see how easily this virus is capable of spreading from person to person. World Health Organization (WHO) Director-General Margaret Chan says the present outbreak “has pandemic potential” but that “it is too early to say whether a pandemic will actually occur”.
Update: This outbreak is now officially a pandemic.

4. How many people have been affected by swine flu?
The number is growing – click here for the latest news.

5. Is there any treatment for swine flu?
Vaccines are available against H1N1 influenza but it is not known how effective they are against this strain. WHO says the virus appears to be susceptible to the influenza drug Tamiflu (oseltamivir), and Relenza (zanamivir). It is not known if resistance to these drugs will occur.

6. How does swine flu spread?
Influenza viruses are transmitted through coughing or sneezing by people infected with the virus. People may become infected by touching something with the virus on it and then touching their mouth or nose, so frequent hand washing is a good idea. You cannot get swine influenza from eating cooked pork or pork products.

7. Has swine flu infected humans before?
Sporadic human infections with swine flu occur regularly but not frequently, e.g. one or two a year in the USA. Most commonly, these cases occur in persons with direct exposure to pigs. There are a few previous cases of one person transmitting swine flu to others.

8. What are the symptoms of swine flu?
The symptoms of swine flu in people are similar to the symptoms of regular influenza, including fever, lethargy, lack of appetite and coughing. Some people with swine flu also have reported runny nose, sore throat, nausea, vomiting and diarrhea.

9. Should I travel to Mexico / the USA?
The World Health Organization (WHO) is not presently advising against travel to Mexico or the USA. National governments may be offering different advice (check locally). Travellers to affected areas are advised to consult a doctor immediately if they show signs of flu-like symptoms.

10. More information:

• CDC
• WHO
• UK HPA
  • UK HPA pandemic influenza FAQ
  • UK national framework for responding to an influenza pandemic
• MicrobiologyBytes: Influenza

11. Are we all going to die?
Probably not. Every year many thousands of people around the world die as a result of influenza, a fact which goes largely unreported. The number of deaths increases in epidemic years. Pandemics (worldwide epidemics) occur unpredictably every 10-30 years. Millions of people die, billions survive.

Update: 10 more things you should know about H1N1 (swineflu)

Today’s post is from guest blogger Helen Fry, who is a student at the University of Leicester.

MicrobiologyBytes welcomes guest bloggers who would like to contribute occasional posts which conform to the style and content of this site. If you would like to be a guest blogger here, please email your post with a completed copyright release form to me at: alan.cann@gmail.com

A quick glance at the British National Formulary and it’s easy to see just how many antibiotics are licensed for use in the UK. What is more difficult to see is how many antiviral agents are available, and this is because there are much fewer. The only viral diseases with treatments listed in BNF 57 are HSV, VZV, HIV, RSV, viral hepatitis and influenza. Viruses are the most abundant ‘lifeforms’ on the planet and there is a huge diversity of viruses that cause disease in humans. Viral disease, although often milder than bacterial or eukaryotic disease, accounts for a major burden on the health service and is a considerable cause of morbidity and mortality. Some viral diseases cause very severe infections and are a heavy global issue, such as HIV and viral diarrhoea (a major cause of infant and childhood mortality in countries without safe drinking water). So if viruses are so abundant and are such a global health pest, why are there so few antiviral agents?

There are several reasons why this is the case. First there is the difficulty of researching viral disease. Most pathogenic bacteria can be cultured and investigated fairly easily, with some notable exceptions such as TB and Chlamydia trachomatis. Culturing and investigating viruses is a lot harder, as it requires cell culture methods, where the appropriate line of eukaryotic cells is grown up and infected with the virus. This means that the virus cannot be studied directly, as with a growing population of bacteria, and because they are so small they can only be visualised via electron microscopy (The impact of cell culture sensitivity on rapid viral diagnosis: a historical perspective). There are non-culture based detection methods, but these only confirm the presence of the virus, they do not allow it to be studied. Viruses do not release any compounds on their own, any proteins made are produced in the host cell, whereas bacteria release toxins and chemotactic agents, quorum sensing molecules and siderophores, to name a few. This makes them easier to study. The fact that viruses are harder to study means that less is generally known about them, and it is a lot harder to identify potential targets for antivirals. On the other hand, viruses have much smaller genomes (on the whole, with some obvious exceptions), meaning that the genomes can be sequenced easily (Role of Cell Culture for Virus Detection in the Age of Technology).

Once a virus has been fully characterised, despite the difficulties, it is still problematic to make useful antiviral agents, and even the ones licensed in the UK are often quite toxic. This is for several reasons. Since the most important part of the virus life cycle takes part inside host cells antivirals often have to penetrate the cell in order to be effective. This means that the drug has to be highly specific for virally infected cells or risk being toxic to healthy cells. The viruses use host cell machinery to replicate themselves, meaning that a drug targeted against this part of the cycle risks affecting genome replication in healthy cells unless a virus specific target can be identified. Bacteria are prokaryotes, which mean that their cells are highly different to ours and it is often a simple matter of identifying a difference between our cells and theirs, and finding a molecule that interacts with it, such as the beta-lactams and cell wall synthesis. Antivirals have similar issues to antiprotozoals, in that finding a compound active against the microbe is not that hard, the difficulty lies in finding one that does not interact with host processes and is therefore non-toxic.

Finally, however, it all comes down to money. Drug development is now a process that is left exclusively to pharmaceutical companies due to its prohibitive costs, and since they are primarily a business rather than a service, all activity undertaken by them will inevitably be profit driven, rather than need driven. Bringing a drug to market now costs several million US$ and taken over 10 years from target identification to phase IV clinical trials. It is therefore a huge investment, and the drug companies want to be as such as possible that their drug will make it to market and will make as much money as possible before the patent runs out. Since patents last for 20 years, a drug may only have 5 years to make back the money it took to develop before cheaper generics can be made. This has caused companies to focus on drugs that are least likely to fail trials due to toxicity and that will make the most money in a short amount of time. Therefore the focus has been on lifestyle drugs that people will take every day for years on end, such as statins and antihypertensives, that have a low risk of toxicity and are well established in doctors’ prescribing pads. HIV therapy has benefited from this, as HIV+ people will need to take their medication every day for the rest of their lives. This, along with the fact that HIV is a rapidly fatal disease without medication meaning that drug companies can charge almost what they like for them, has meant that the number of effective, less toxic antiretrovirals is increasing and is already fairly big in comparison to other viral illnesses. Drug companies will risk producing drugs that are more likely to be toxic if they can charge a large amount for them once approved. This is usually the case for life-threatening illnesses, explaining why chemotherapy for cancer costs so much (in the tens of thousands for a single cycle in some cases), but is quite good these days, at least for the common cancers.

The incentive of money can be seen with the influenza drugs. Not many people have the need for influenza antivirals, since there is a pretty good vaccine produced each year for those at risk, and those not in high risk groups do not tend to suffer from severe enough disease to warrant treatment with anything other than blankets and Lemsip. So why are there two good drugs sitting on the market when they are not needed? The answer lies with the government who, fearing an approaching flu pandemic (we are due for one) decided to stockpile the anti-influenza drugs before they were widely used and resistance developed.

The biggest burden of viral disease, as with most infectious diseases, lies in developing countries. They are the worst hit by the HIV pandemic, suffer outbreaks of haemorrhagic fevers, are plagued by water borne viral diarrhoeal diseases and various other viral nasties. However, since they for the most part do not have the capital to fund a national health service and the people cannot afford medications themselves, these countries and their endemic diseases have been largely ignored by the drug companies due to the lack of profit potential. This means that the countries worst affected by HIV are the ones who do not have access to effective antiretroviral therapy, and that children die in the thousands because of viral diarrhoea. Some drug companies are starting to research third world diseases, but progress is slow and funding is not the best. Since we in the west need medications we cannot boycott the companies, and allowing patents to be extended would only put more strain on the already overwrought NHS. However, there needs to be a shift in attitudes towards making the companies more responsible for the drugs they develop.

Related:

• MicrobiologyBytes: Antivirals
• GSK to provide cheap drugs to the developing world
• Targeting inside-out phosphatidylserine as a therapeutic strategy for virus diseases