Global health and Community medicine--1

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EDITORIAL

Dear Reader, Welcome to the Global and Community Health section of the inaugural edition of the LSJM. My panel and I hope, in this section, to inform, educate and stimulate debate on a wide range of healthcare issues, both at home and abroad.

We recognise the short and precious nature of your free time and with this in mind have selected articles that appeal due to their originality, importance and clarity. Exposés on resurgent tropical illnesses and calls for worldwide vaccination programmes sit with a unique piece examining the effect of “bird flu” on smallholder poultry farming, in what I hope you will find to be an interesting and entertaining section.

Two of the articles illustrate neglected diseases, namely sleeping sickness and chikungunya, which “Big Pharma” and governments have ignored, and that are now increasing in virulence. I believe though, that slowly but surely, change is afoot in global health. As you will read in our news area, Glaxo-Smith-Kline’s pledge to simultaneously discount the price of medicines to developing countries and to create a drug patent pool is an encouraging sign. This, together with the advent of philanthrocapitalism, the application of techniques borrowed from successful businesses to create more efficient and transparent charities (as seen in the Bill and Melinda Gates Foundation) will, I hope, be a transforming force in the future.

This edition of the journal is themed “unhealthy behaviours.” We link to this theme with a fascinating article comparing food addiction to drug addiction. Obesity has reached epidemic proportions worldwide and is now a major contributor to the global burden of disease. Time is rapidly running out for governments to act, before we are faced with a crippling healthcare crisis and this socially acceptable “unhealthy behaviour” merits more serious engagement throughout society.

Community health has undergone a not-so- quiet revolution in the past few years, with a greater emphasis being placed on preventative medicine. The tragic death of Jade Goody has done much to highlight the importance of cervical cancer screening, and our section boasts a topical article dealing with possible screening initiatives for cervical cancer in the developing world, together with the potential ramifications of nation-wide vaccination projects in these countries.

We live in a world where every year 1.4 million children under 5 die of diseases that could have been prevented by routine vaccination.1 Such figures are beyond the pale and as future medical professionals we would do well to remember the words of the Global Health Council, “When it comes to global health there is no them, only us.” I hope that the LSJM in the future will do much to illustrate the dire need for doctors and medical aid in the developing world and that this will encourage some of you to lend your extraordinary talents to those in need away from these shores.

I would like to end by thanking my co-ordinator Katherine Sharrocks, my panel, peer and expert reviewers and of course the exceptional authors whose work I have had the privilege of reading. Editing this section broadened my horizons greatly and I hope that engaging with these articles does the same for you.

This journal can only improve with the participation of medical and allied health students. With this in mind, if you have any comments, criticisms or suggestions then please write to gchm@thelsjm.co.uk, with “Letters to the Editor” in the subject line. Also, if you are interested in writing for the publication then do submit your work by email. I look forward to hearing from you.

Best wishes Vishal Navani Section Editor of Global and Community Health References: Illustration: Robert Hare

1.

http://www.who.int/immunization_monitoring/diseases/en/

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NEWS “Big Pharma” GSK in price slash and patent pool pledge Sandra Sadoo Year 4 Medicine, Imperial College Drug giant Glaxo-Smith-Kline (GSK) will offer medicines at a 25% reduction to 50 developing countries, affirmed CEO Andrew Witty at Harvard Medical School.

This groundbreaking move by the company involves the sharing of 800 of its patents to third parties researching neglected diseases such as tuberculosis.

It has been pledged that 20% of profits made from these selected countries will be invested back into the development of infrastructure such as health clinics. Middle-income countries such as Brazil and India will also be proposed a cost cut. Drug treatments for malaria, hepatitis B and asthma are amongst those included in the scheme.

These proposals came 12 days after GSK showed itself to be another victim of the economic downturn by axing 6,000 jobs worldwide.

It is hoped that the world’s second largest pharmaceutical company has raised the bar and will challenge other pharmaceuticals to question their practices. In Witty’s words, “Society expects us to do more in addressing these issues. To be frank, I agree. We have the capacity to do more and we can do more.”

Witty acknowledged that the investment costs to Glaxo are likely only to extract up to £2m of the £30m that Glaxo make annually from its sales to the lowest-income countries.

The minister for international development, Ivan Lewis said to the Guardian, “We’re all concerned about the economic circumstances we’re living in and the danger that that will push an increasing number of people into poverty”. Lewis believes that “Challenging pharma to do their bit ... is entirely legitimate.”

Naltrexone is a drug which blocks receptors in the brain responsible for the ‘highs’ drinking can produce. It has been available in daily tablet form for some time, but in 2006 the United States Food and Drug Administration approved a long-lasting formulation, which can be injected into muscle once a month. A small study has been undertaken in Cambridge, Massachusetts, which shows the injections decrease the frequency and severity of drinking sessions.

Heavy drinking represents an enormous public health burden across the globe. David Rosenbloom, a specialist in substance abuse from Boston University, says these injections may have a “huge” significance for public health, and he envisages them being offered to repeat drink-drive offenders.

At a time when the public health implications of binge drinking are constantly in the news, Naltrexone injections may yet prove a real ‘shot in the arm’ in the fight against alcoholism.

Published previously in ‘Perspectives’ (UCL MEDSIN). Taken with permission from magazine and author

A new weapon in the arsenal against cervical cancer The fight against cervical cancer has been augmented with a series of defining blows; safe and effective vaccines have been developed against oncogenic Human papilloma viruses (HPV), national vaccination programmes have been rolled out in several countries and public awareness about the condition has increased. These events should fuel a reduction in the rates cervical cancer and its associated mortality. However, these changes have benefited a few lucky countries. In many low resource countries, where the prevalence of HPV and cervical cancer are higher, a solution still needs to be found. Results from a cluster-randomised controlled trial in rural India may provide an answer.

It is clear that the sense of social responsibility of pharmaceutical firms is increasing. The anticipations are that knowledge-sharing and more affordable drugs for impoverished countries will accelerate the development of new drugs and broaden the access of the world’s poor to essential medicines.

Sankaranarayanan et al showed a significant reduction in advanced cervical cancer incidence and mortality using a single round of HPV screening compared to cytology and visual inspection of the cervix with acetic acid (VIA).1 HPV screening was found to be more objective, reproducible and easier with regards to training.

However, it was more expensive than other screening programmes.1 Cytology or VIA can then be used in HPV-positive patients to assess the risk or presence of cervical cancer respectively.2 Those without cervical cancer can then receive cryotherapy reducing the risk of progression to malignancy. The authors suggest that HPV screening should not be used in women under the age of 30 because of the tendency of these lesions to regress thus discarding the need for treatment.1 This study provides an encouraging option for resourcelimited countries to curb the incidence of cervical cancer and its associated socio-economic implications.

A Shot for Alcoholics?

Reference

Michael Malley Year 4 Medicine, University College London m.malley@ucl.ac.uk

2.

Glaxo nonetheless have been criticised in their decision to withhold their HIV patent rights, due to a conviction that “other efforts are addressing the need for anti-virals”. Lewis hopes that in a meeting with executives of rival drug firms, he will be able to increase the participation of companies in such a patent pool.

1.

Sankaranarayanan R, Nene B, Shastri S et al. HPV Screening for Cervical Cancer in Rural India. N Engl J Med 2009;360:1385-94.

Schiffman M and Wacholder S. From India to the World - A Better Way to Prevent Cervical Cancer. N Engl J Med 360;14

You would not think it would be a problem giving shots to alcoholics. However, a different type of ‘shot’ may well help recovering alcoholics – a monthly injection to prevent craving for alcohol.

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REFLECTIVE PIECE

Influenza A(H1N1): Echoes of the Spanish Flu? Mukhtar Bizrah BSc (Hons) Year 4 Medicine, St. George’s University of London m.bizrah@gmail.com For many, the Flu may be an inconvenient state of health one has to put up with once or twice a year. For wary historians, however, the emergence of a pandemic Influenza A(H1N1) flu outbreak may mean the beginning of a humanitarian crisis. The last global outbreak was that of the Hong Kong flu in 1968, killing 3 million people. The true global implications of a flu pandemic, however, may be more accurately reflected by the Spanish flu in 1918. Killing 50 million people around the globe, it is one of the deadliest known events in human history.

Conflict of interests: Mukhtar is an executive member of the LSJM.

To date (5 June 2009), the World Health Organisation (WHO) has confirmed 19273 cases of swine flu in 48 countries. Of the 117 resultant human deaths, 97 have occurred in Mexico and 17 in the United States (US). Yet the true number of those infected is estimated to be much higher. Although 10053 cases have been reported in the US to date, the director of the National Center for Immunization and Respiratory Diseases, Dr Anne Schuchat, stated that “this is the tip of the iceberg -- We estimate more than 100000 cases.” This may not come as a surprise seeing that most people with flu symptoms do not see their family physician. Of those that do, a considerable number do not have swabs taken for laboratory analysis.

Is an H1N1 pandemic inevitable then? As the WHO gets closer to raising the pandemic alert level from phase 5 to 6, it has laid great emphasis on the fact that this is simply a reflection of demographical spread, rather than severity of illness. Europen Union (EU) Health Commissioner Androulla Vassiliou comments: “It is very likely that we will reach a pandemic, but this does not mean that it will be deadly.” More questions are consequently being posed regarding the true virulence of the virus and impact of an H1N1 pandemic.

Wendy Barclay, chair of Influenza Virology at Imperial College in London, analysed influenza A(H1N1) genes to find that H1N1 has “no genetic features of a highly pathogenic virus at all.” She told The Lancet Infectious Diseases that rather “it looks as though this virus should target the upper respiratory tract and not the lung”.1 Nancy Cox, the chief of the Center for Disease Control (CDC) influenza division has also stated that the swine flu is not as ‘virulent’ as the Spanish flu causing the 1914 outbreak, and this over the past few weeks has become more apparent. As a matter of fact, it may be much less deadly than the ordinary flu, which is estimated to kill around 36000 people in the US every year.2 Yet there are numerous unknown factors affecting ease of spread and individual response to H1N1 flu. Individual immunity is a principal factor, which is why very young and very old individuals are at greatest risk of mortality from ordinary flu. To this date, it is still not certain if humans possess any immunity to H1N1 flu. The CDC has

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Image: Electron microscopy image of the newly identified H1N1 influenza virus: US Center for Disease Control and Prevention

stated that older populations may have immunity against H1N1 virus, as 64% of the cases reported to the CDC are individuals aged 5-24 years. But this remains uncertain as other factors such as young people travelling more may have come in to play.

A major concern is spread of the virus to developing countries in the southern hemisphere, whose populations according to Dr Chan, Director-General of the WHO “are most vulnerable” and as a result “should prepare to see more than the present small number of severe cases.” Charities such as Oxfam have repeatedly warned that these populations are at great risk due to shortage of potentially life threatening treatments.

There seems to be one certainly common theme in much of our knowledge about H1N1: Uncertainty. Dr Nikki Shindo, a WHO medical health officer, may have described the current situation best: “The worst-case scenario is the virus will mutate and become Tamiflu (Oseltamivir)-resistant. The best-case scenario is that it causes only mild illness and continues to respond to Tamiflu.” It is too early to make definitive conclusions regarding the aftermath of a looming pandemic, and only time may give the answer. For the time being, however, the re-emergence of a pandemic as deadly as the Spanish flu seems like a remote scenario.

Reference 1.

2.

Shetty P. Preparation for a Pandemic: Influenza A H1N1. The Lancet Infectious Diseases Vol. 9, Issue 6, pp. 339-340 June 2009.

Thompson WW et al. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA 2003; 289(2):179-186.

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PERSPECTIVE

From ‘Equasy’ to ‘Obesity’ Haran Sivapalan BA (Hons) Year 4 Medicine Kings College London haran.sivapalan@kcl.ac.uk doi:10.4201.lsjm/gch.002

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Obesity exhibits the bio-psychosocial properties of a serious addiction, albeit a socially tolerated one

On 11 February 2009, the UK Home Secretary Jacqui Smith rejected suggestions from the Advisory Council on the Misuse of Drugs (ACMD) to downgrade ecstasy from Class A to Class B. Ecstasy or MDMA (3,4 methylenedioxy-N-methamphetamine), notorious for its use within the rave scene, therefore remains on the list of the most harmful drugs along with heroin and crack cocaine.

Previous obduracy of the government on this matter, with its rejection of the Home Affairs Committee report in 2002 and the Runciman report in 2000, may have spurred the chairman of the ACMD, Professor David Nutt, to write an article comparing the risks of ecstasy use to that of horse-riding. Published in the Journal of Psychopharmacology, the article, entitled ‘Equasy: an overlooked addiction with implications for the current debate on drug harms, ’ served to highlight the illogicalities in society’s attitude to the harm of illicit drugs in relation to the harm of other more socially accepted activities.

Extending from these notions, it may be argued that the ingestion of highly calorific, high-fat and unhealthy foods is harmful in the context of the present obesity epidemic. Would policies similar to those implemented to control illicit drugs be successful in curtailing the exigencies of the obesity trend?

The classification system, stipulated by the Misuse of Drugs Act passed in 1971, discriminates drugs into three classes: A, B and C, on the basis of harm. The term ‘harm,’ however, is nebulously

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defined and Nutt castigates the system’s ‘arbitrary foundations with seemingly little scientific basis. ’ As an alternative, Nutt suggests that harm should be evaluated in three domains: physical harm, dependence and social harm. Unhealthy foods can be argued to be harmful in each of these ways.

Physical Harm While high-fat foods may not be physically harmful in terms of acute toxicity, their chronic ingestion causes physical disease both directly and indirectly, through the promotion of weight gain and obesity. Obese females with a Body Mass Index exceeding 35kg/ m2 have a 93-fold increased risk of developing type II diabetes mellitus. In addition, obesity increases the risk off cerebrovascular and gallbladder disease. In terms of the direct repercussions of a high-fat diet, studies on human subjects suggest a causal role in vascular endothelial dysfunction and hepatic steatosis. In contrast to intravenous drug administration, oral ingestion of food is not associated with any serious secondary harm.

Dependence Applying the concept of dependence to foodstuffs remains abstruse, but there is a burgeoning body of evidence suggesting obesity has psycho-physiological commonalities with drug addiction. Administration of calorific foods and drugs has both been shown to activate mesolimbic dopaminergic reward networks in the brain. Similarly, relatively low striatal D2 dopamine receptor

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PERSPECTIVE densities may subserve a ‘reward-deficient’ state in both obese individuals and drug addicts that drives compulsive eating and drug use respectively. Furthermore, dysregulation in the orbitofrontal cortex and other prefrontal areas may form a common neuronal substrate underlying food and drug craving behaviours. Repeated use and craving are two fundamental features of psychological dependence, such as that seen in long-term users of cannabis.

Chronic ingestion of high fat foods, however, does not induce a physical dependence typified by withdrawal symptoms.

Social Harm The social ramifications of obesity primarily include considerable economic costs. Obesity generates direct costs, such as those of diagnosis and treatment, as well as latent costs, such as from lost income due to morbidity or mortality. In the USA, such costs amounted to $68.8 billion for the year 1990 illustrating that this public health problem is of similar economic magnitude to drug addiction. Other societal harms may possibly comprise damage to psychological wellbeing. Unlike other drugs, notably alcohol, high-fat foods do not exert social damages through the effects of acute intoxication.

There are other conspicuous differences between obesity and drug addiction. Food is necessary for survival, whereas drugs are not.

The composition of what is deemed ‘unhealthy food’ is subject to more heterogeneity than the specific active substance of a drug.

Given the parallels between drug addiction and excessive caloric dependence, however, the question arises whether public health policies used to regulate the supply and demand of drugs can be applied efficaciously to tackle obesity.

A renewed and energetic public education campaign could be used to reduce the demand for unhealthy foods. This would involve the dissemination of information about their associated health risks to schools, places of employment and through the media.

The potency of this method has precedence in smoking cessation campaigns, which have been effectual in reducing nicotine use.

Despite this, educational strategies require long periods to evoke change and it is questionable whether this strategy alone would abate an obesity epidemic.

cost to the consumer and generate a disincentive to smoke or drink. A similar system of tax on unhealthy foods could favourably modify dietary choices. Additionally, as food has a lesser propensity to cause dependence in comparison to nicotine, demand is likely to be more price elastic. While simultaneously dissuading unhealthy food consumption, revenue created from these schemes can be used to fund healthcare. Alternative economic strategies involve placing minimum prices on unhealthy foods. One major criticism of applying these policies is that they penalise poorer people far more than those with higher disposable incomes.

Conclusion Clearly, obesity exhibits the bio-psychosocial properties of a serious addiction, albeit a socially tolerated one. Whereas the Equasy example questioned the aggrandisement of drug-related harm compared to other socially accepted harms, a parallel issue is the relative leniency granted towards unhealthy foods. With the prevailing obesity epidemic, a period of cultural upheaval in the attitude toward these foods is required. High-fat, calorific, ‘junk’ foods are reinforcing drugs that drive compulsive eating and as such must be subjected to stringent social, economic and legal policies.

If the obesity problem is to be solved, the state, producers and consumers of food must all grant credence to the notion of obesity as an addiction.

Reference List •

•

• •

•

Nutt DJ. Equasy – An overlooked addiction with implications for the current debate on drug harms.

Journal of Psychopharmacology 2009; 23 (1): 3-5.

Nutt DJ, King LA, Saulsbury W, Blakemore C. Development of a rational scale to assess the harms of drugs of potential misuse. The Lancet 2007; 369: 1047-1053.

Jung RT. Obesity as a disease. British Medical Bulletin 1997; 53: 307–321.

Motomura W, Inoue M, Ohtake T, Takahashi N, Nagamine M, Tanno S, et al. Up-regulation of ADRP in fatty liver in human and liver steatosis in mice fed with high fat diet. Biochemical and Biophysical Research Communications 2006; 340: 1111-1118.

Volkow ND, Wise RA. How can drug addiction help us understand obesity. Nature Neuroscience 2005; 8: 555-560.

Legislation The success in tapering the prevalence of nicotine use may also stem from legislative measures. A minimum age for purchasing tobacco and, more recently, the banning of smoking in public areas, clearly limit the opportunity to indulge in nicotine use. In theory, similar measures can be applied to curb obesity. While outlawing certain foods may be construed as extreme, more moderate measures, such as nationwide restrictions on the types of food that can be sold in schools, could prove beneficial. Like the nicotine precedent, legal restraints can be imposed on advertising and may enforce the inclusion of health warnings on food packaging. Such legal schemes are, however, clearly contentious in that they present a potential affront to civil liberties and consumer freedoms. Such moves would also undoubtedly engender a powerful political lobbying and subversive response from the processed food industry, one of the most influential, wealthy and well-organised groups in our society.

For licit drugs such as nicotine and alcohol, pricing is an important factor in the regulation of public usage. Heavy taxes increase the

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REVIEW

Poultry vs. Poverty: The Social Impact of HPAI on Smallholder Poultry Farming in the Developing World Peter D. Liddle BA (Hons) Year 1 Medicine, King’s College London peter.liddle@kcl.ac.uk doi:10.4201.lsjm/gch.005

The term “developing” in the context of countries and economies is employed here strictly in the statistical sense as defined by the United Nations Statistics Division (UNSD), and should not be considered as a judgement of relative development in a broader sense; or an acceptance that such comparisons are possible or useful.

For the full article and references see thelsjm.co.uk.

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Where the rooster crows, there is a village.

Shambala proverb, Tanzania8

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Although recognized in fowl for over one hundred years, and reported formally in 1959,1 Highly Pathogenic Avian Influenza (HPAI) captured widespread public attention early in 1997, spurred by the first reported human infections of the H5N1 subtype in Hong Kong.2 The emergent zoonotic properties of the virus provoked rapid mass media coverage, and 6 fatalities amongst the initial 18 laboratory confirmed cases fed urgent speculation of an impending human pandemic. Whilst the Hong Kong outbreak was contained and controlled with relative rapidity, subsequent human infections in other regions of China were reported throughout 2003/4, and in January 2005 the World Health Organization (WHO) modelled a best case pandemic scenario, projecting excess global deaths ranging from 2 – 7.4 million.3 Since this alarming analysis, however, it has become apparent that HPAI viruses, including the H5N1 subtype, have the propensity to bind deep within the lungs, in contrast to more common seasonal influenza viruses which attach to cell linings in the nose and throat.4, 5 This seems to impede human uptake of the virus, both in terms of zoonotic and human-human transmission.2 As a result, whilst occurrences have spread geographically throughout South East Asia, Africa and Europe, the most recent WHO update reports a much smaller figure than predicted: 407 laboratory confirmed cases of human H5N1, 254 of which have resulted in fatality.6 Due in part to comprehensive media coverage of the concerns of public health specialists, the general academic and public perception of HPAI was initially one of understandable apprehension. The vast majority of literature throughout 2004/5 concerned risk assessment, damage limitation, and containment strategies in the first instance; followed by financial and industrial economic analyses as costly public health measures were employed

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REVIEW in South East Asia and Africa. However, as human HPAI has yet to approach pandemic levels, public opinion seems increasingly to consider the virus to be the latest in a string of unjustified public health scares, following variant Creutzfeldt-Jakob Disease (vCJD) and Severe Acute Respiratory Syndrome (SARS).

Unfortunately, this apparent reduction in concern is not representative of the lessening global significance of HPAI, and undermines a vast array of social and economic impacts which have yet to be assessed to the necessary degree. The fundamental importance of smallholder poultry farming in the context of diet, development, poverty alleviation and gender equality throughout non-Western countries is broadly recognized,7, 8, 9, 10, 11 and compels a more holistic analysis of the negative effects of HPAI and associated containment measures.

The Global Importance of Poultry The International Food Policy Research Institute estimate that 30% of animal protein consumed globally is derived from poultry products, representative of a 10% increase since 1990.12 Furthermore, this figure is expected to increase to 40% before the year 2015, and meeting this demand has rendered poultry production the fastest growing element of the global meat industry.9 In the context of avian influenza, it is important to recognize that a huge proportion of this production and consumption occurs in the regions of Asia and Africa: economies within which the overwhelmingly predominant farming system is that of rural smallholder poultry rearing in local communities.

Family Poultry (FP) is defined by the International Network for Family Poultry Development (INFPD) as the extensive or semiextensive rearing of poultry in small numbers, through non-salaried family labour.11 This form of poultry production accounts for 84% of Africa’s poultry flock13; some 1.17 billion birds8; whilst surveys in Kenya14 and Malawi15 indicate that chickens are kept by 90% and 95% of the populace respectively. Similarly, more than 90% of households in a survey conducted in Western India16 and 89% of households in rural Bangladesh17 keep family poultry. These statistics demonstrate the ubiquitous nature of smallholder poultry rearing throughout the developing world, and bring the negative impact of HPAI and associated control measures into perspective.

Family Poultry as a Means of Poverty Alleviation Whilst United Nations Millennium Development Goals (MDGs) aim to have halved extreme hunger globally by 201518 recent figures estimate 792 million individuals continue to suffer malnutrition.19 Branckaert and Guèye (2000) assert that sufficient intensification of agriculture has not developed in Low-Income Food-Deficit Countries (LIFDCs) to feed growing populations, and thus larger tracts of land will have to be reallocated to staple food crops in these nations. As arable land is a finite resource, this in turn will ultimately be prioritised over pasture and fodder, negatively impacting livestock populations. As a result, many development projects have recognized the importance of poultry as a livestockderived protein resource and a means of financial stability that does not require arable land to rear. It is widely supported that alternatives such as these must be developed if MDGs are to be achieved.11, 19, 20

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Why poultry is such a crucial tool for poverty alleviation and international development10, 21 • poultry is a near ubiquitous resource in developing countries • relatively low cost technology and low initial financial investment • often delegated to marginal groups, such as women, children and the elderly • land is not required for successful poultry production

Many family poultry schemes have already been successful in the developmental context. Chitikuro and Foster22 calculated that in Central Tanzania, an average flock size of 5 chickens increases the income of women by US$38/yr, representative of a 10% income increase. An alternative study conducted in N’Djaména, Chad23 revealed that profit from sales of poultry related produce was spent variously between clothing, food, medicine, soap, and reinvestment, suggesting that economic benefits are widespread and generate income in excess of self-sustenance. Kabatange and Katule24 demonstrate that one chicken laying 40 eggs at 50% hatchability will, in subsequent generations, produce more meat over 5 years than a range-fed cow, which itself will not reach slaughter weight for 5-7 years.

Given the significance of global malnutrition, and the apparent viability of FP poverty alleviation models, it follows that the true threat of HPAI may lie not in the human pandemic, but the jeopardising of poultry-based development initiatives, and the insurance and economic stability achieved through smallholder poultry farming internationally.

Women, Children and Chickens: Gender Equality through Poultry In the context of FP production, it is highly significant that poultry farming is a realm of agriculture which, throughout Africa and Asia, is traditionally associated with at-risk groups: primarily women, children and the elderly7, 8, 11, 25 and within which economic contributions from women are often deemed more acceptable.26 For this reason, FP development programs are, in some cases, able to address the issue of gender inequality. One particularly lauded example of this approach is an initiative termed The Bangladesh Poultry Model.26 The Bangladesh Poultry Model (BPM) is derived from the Bangladesh Smallholder Livestock Development Project, first implemented in 1991.27 It specifically targeted women in rural areas, enhancing productivity of poultry rearing in the Dhaka region of Bangladesh. Through poultry skills, education and the organization of upstream and downstream enterprises (e.g. training of chick rearers, feed mixers and poultry healthcare workers) the project both improved poultry production in the region, and increased the confidence and financial stability of the women involved.27 The BPM and similar development schemes are of invaluable benefit to their communities, and are jeopardised by HPAI and associated control measures.

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REVIEW References The Social Impact of HPAI 1.

Whilst the direct risk posed to human health by H5N1 is undoubtedly a reality, the current lack of human HPAI uptake ought not to imply a reduction in impact, especially in the related academic literature. It is clear that; in light of the broad and complex role played by poultry in the developing world both at the community and household levels; the “participatory, holistic, trans-disciplinary approaches” advocated by Guèye8 and others are entirely necessary, particularly in the realms of poverty mitigation and gender equality.

In Soth East Asia, countries hardest hit by avian influenza include Cambodia, Indonesia, Thailand and Vietnam,28 whilst Nigeria, Burkina Faso, Cameroon, Cote d’Ivoire, Djibouti, Egypt and Sudan represent the current course of the virus in Africa.8 In the Vietnamese example, studies29 show production in smallholder poultry farms to have decreased by 57% in 2004; the first year of avian influenza outbreak; whilst sales of smallholder poultry suffered a 150% decrease in the same year. Furthermore, the biosecurity measures recommended by public health organizations are heavily reliant on widescale avian depopulation9 resulting in a direct 10-15% loss of annual income for Vietnam’s poorest families – a figure that is likely to increase to almost 50% when accounting for the fact that such families are unable to consume their own produce.11 Worse still, these impacts are not limited to the short term, but potentially extend far into the future, as the implementation of new biosecurity and confinement measures, stringent licensing and inspection effectively favour commercialization, and drive smallholder poultry underground.31

2.

3.

4.

5.

6.

7.

8.

9.

10.

Food and Agriculture Organisation of the United Nations. Avian Influenza. EMPRES Transboundary Animal Diseases Bulletin. 2004;25:1-9.

World Health Organisation. H5N1 Avian Influenza: Timeline of Major Events [monograph on the Internet]. 2007 [cited 2009 Feb 11]. Available from: http://www.who.int/csr/ disease/avian_influenza/Timeline_07_Aug27.pdf World Health Organisation. Avian Influenza: Assessing the Pandemic Threat [monograph on the Internet].

2005 [cited 2009 Feb 11]. Available from: http://www. who.int/csr/disease/influenza/H5N1-9reduit.pdf Shinya K, Ebina M, Yamada S, Ono M, Kasai N, Kawaoka Y. Avian Flu: Influenza Virus Receptors in the Human Airway. Nature. 2006;440:435-36.

Van Riel D, Munster VJ, de Wit E, Rimmelzwaan GF, Fouchier RA, Osterhaus AD, et al. H5N1 Virus Attachment to Lower Respiratory Tract. Science. 2006;312:339.

World Health Organisation. Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO [monograph on the Internet]. 2009 [cited 2009 Feb 11]. Available from: http://www.who.int/csr/disease/avian_influenza/ country/cases_table_2009_02_11/en/index.html Guèye EF. Gender Aspects in Family Poultry Management Systems in Developing Countries.

World’s Poultry Science Journal. 2005;61:39-46.

Guèye EF. Evaluation of the Impact of HPAI on Family Poultry Production in Africa. World’s Poultry Science Journal. 2007;63:391-400.

Mack S, Hoffman D, Otte J. The Contribution of Poultry to Rural Development. World’s Poultry Science Journal. 2005;61:7-14.

Permin A, Pederson G, Riise JC. Poultry as a Tool for Poverty Alleviation: Opportunities and Problems Related to Poultry Production at Village Level [monograph on the Internet]. Australian Centre for International Agricultural Research; 2000 [cited 2009 Feb 11]. Available from: http://www.kyeemafoundation.org/ rural_poultry/content/SADC_Workshop/pr103chapter29.pdf

In the context of the extensive and hugely positive impact of smallholder poultry rearing throughout the developing world, the true extent of the threat posed by avian influenza becomes apparent. Whilst current preventative or curative measures have the propensity to cull and contain, these practices in isolation may severely undermine, if not destroy the contributions of smallholder poultry rearing to international development.

Furthermore, restrictive legislation could potentially commercialize poultry production to the extent that rural smallholders could be effectively encouraged to rear poultry in clandestine, concealing outbreaks of HPAI, and increasing the danger of a human pandemic.11, 31 In Thailand, studies have shown that qualitative analysis of local attitudes, and the provision of culturally-contextualized information regarding HPAI has stimulated locally derived control measures.

In addition, although costly for governments, financial compensation for rural farmers also makes concealment of HPAI outbreaks less likely, and mitigates economic losses to some extent. Such culturally and locally contextualized measures, it appears, are able to influence poultry rearing practice in smallholder environments, and thus, in conjunction with carefully planned biosecurity measures, may provide an avenue through which both the public health and broader social impacts of HPAI can be more effectively minimized.

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ARTICLE

Chikungunya Cholan Anadarajah

Year 4 Medicine, Barts and the London ha06199@qmul.ac.uk doi:10.4201.lsjm/gch.001

Source: Wellcome Images

For the full article and references see thelsjm.co.uk.

Overview Chikungunya is a viral haemorrhagic fever caused by an alphavirus, which belongs to the Togaviridae family.1 This single-stranded RNA virus is also known as ‘Buggy Creek virus’ due to it causing boggy and creeky joints, as well as other arthralgic symptoms.2 It is transmitted via the Aedes aegypti (yellow fever mosquito). Recent research shows that the virus may have mutated slightly by altering its genotype, thus enabling the Aedes albopictus (Asian tiger mosquito) to also be a vector.3 Outbreaks have taken place in tropical countries, more recently creating an endemic in India, Sri Lanka and the Maldives. In 2006 34% of the population (about 265,000 people) on Reunion Island caught this virus and of those 237 people died. However, this rare disease is generally not fatal.4 The Chikungunya virus (CHIKV) causes high fever, pain in the joints and rashes on the body. All these symptoms are also characteristic of Dengue – also transmitted via bites from the same type of mosquitoes – leading to difficulty in achieving a definitive diagnosis. Therefore, all other possibilities must be eliminated before diagnosing chikungunya.5 History The first known outbreak of chikungunya took place in 1952 at the border between Tanganyika (now Tanzania) and Mozambique, where the illness was named in the local Makonde language literally meaning “that which bends up” due to it causing the sufferer to maintain a stooped posture.6 It was first described in 1955 by Marion Robinson and WHR Lumsden.7

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The first outbreak in India was in 1963 in the state of Calcutta, followed by outbreaks in 1964, 1965 and 1973. However, the genotype of the CHIKV has mutated and now displays the African genotype as opposed to the original Asian genotype. Through 2006 the epidemic has spread to the neighbouring countries of Sri Lanka, Maldives and the Reunion island.8 Chikungunya virus CHIKV is a positive-strand RNA virus surrounded by a lipid-containing envelope with 2-3 surface glycoproteins that mediate attachment, fusion and penetration. The virus is spherical, 60 to 70nm in diameter, and displays icosahedral symmetry. The nucleocaspid is about 40nm in diameter.9 The complete genome of the CHIKV is 11824 nucleotides long.

The partial sequences of NS4 and E1 genes have been analysed phylogenically to reveal three different CHIKV phylogroups. These were samples from:10 • • •

West Africa Asia East, Central and Southern Africa (ECSA)

The original type of CHIKV that caused the Indian Ocean outbreak belonged to the Asian phylogroup. However, two mutations to the E1 envelope protein, caused it to change to the West African phylogroup. This made the virus more likely to enter mosquito cells and replicate after the insect has fed on the blood of an infected person, causing the re-emergence of the disease.10

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ARTICLE Vector Chikungunya is transmitted by mosquitoes belonging to the Aedes genus, found in tropical and subtropical zones. ‘Aedes’ is derived from the Greek for unpleasant due to the fact that it acts as a vector for many diseases, including dengue and yellow fever. The life span of a typical adult mosquito is 15 days, and they occupy human habitats (living rooms, offices etc).11

Thus treatment for chikungunya mainly consists of symptomatic relief, with analgesics, antipyretics and fluids. Paracetamol is given to relieve the symptoms of fever and joint pain. Bed rest is essential and mild exercise may improve stiffness and joint pains.13 Rudraksha healing (involving spiritual meditations) also touted as a potential homeopathic treatment. However, again there is no conclusive evidence to substantiate this.14

The initial vector for chikungunya was the Aedes aegypti mosquito responsible for transmission in the Asian and ECSA phylogroup.

However, it was noticed that chikungunya still developed in areas where these types of mosquitoes were not present. Aedes albopictus, was then discovered to be a vector for CHIKV. This mosquito is more commonly associated with the West African phylogroup.3 It should be noted that only the female mosquitoes suck blood from humans (undertake hematophagy) and thus the males are not disease vectors. Females need blood to support the development of their eggs. They mainly bite humans, usually 3-4 times a day for a satisfactory meal, injecting saliva which acts as an anticoagulant in the human.12

Prophylaxis Vector control is the most effective way to prevent disease.13 One way of eradicating mosquitoes is to eliminate their habitat stagnant water at homes, schools and work places. Mosquitoes will then not be able to breed and eventually die off.13

Signs and Symptoms On becoming infected there is usually an incubation period of about 3- 12 days when no symptoms are evident, followed by a sudden onset of various symptoms.2

Prognosis Chikungunya is an illness from which most people recover completely. However some, especially tourists, develop joint pains that can last for a few months. 12% of patients will have chronic arthralgia three years after disease onset.1

Most of these symptoms will last a few days, if not a few weeks.

However, research has shown that some patients may have obdurate joint pains for many months. Especially in cases with tourists becoming infected in a tropical country, but still suffer joint pain after returning home.13 Signs and Symptoms3 • high fever up to 39˚C • rashes around the limbs and trunk • headaches • infection of the conjunctiva (potential photophobia) • erythema • flagellate pigmentations on face & extremities • ulcers over scrotum

Futher prophylaxis can be achieved by long-sleeved clothing, insect repellent and the use of mosquito nets at night. Public Education matters. Many may not know how to prevent acquiring disease. It is therefore the responsibility of governments and Non-Government Organisations to educate and also to supply the necessary equipment to ensure disease prevention.

The very few associated deaths are mainly due to poor preventative measures, inappropriate use of antibiotics or lack of resources to treat symptoms. It also has not affected the Western world as yet, though the virus could mutate further and impact the rest of the world.

Referencing 1.

2.

3.

Diagnosis Following a full history and examination, it is important to exclude Dengue as a differential, often done by the presence of haemorrhage. However, the definitive method for diagnosing chikungunya is to undertake an Enzyme-Linked ImmunoSorbent Assay (ELISA) to see if Immunoglobulin M (IgM) is present in the blood.1

4.

Treatment There is no specific treatment for chikungunya. Although vaccine trials took place in 2000, a lack of funding halted research due to a number of factors. Firstly, although many people were being infected by CHIKV, very few people actually died as a result.

Furthermore, most infected individuals were in third world countries which led to a lack of initative amongst “Big Pharma” to invest in research and development. One drug that is being looked into is chloroquine, used in the treatment of malaria. Clinical trials are being conducted to see its use as an antiviral agent against the CHIKV. However, the results are not yet conclusive.3

7.

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5.

6.

8.

9.

10.

McMorran J, Crowther DC, McMorran S et al. chikungunya haemorrhagic fever [online] 2005. Available from: http://www.gpnotebook.co.uk/simplepage. cfm?ID=1523580948 [accessed 2/3/2007].

CBWInfo. Chikungunya fever: essential data [online] 1999.

Available from: http://www.cbwinfo.com/Biological/ Pathogens/CHIK.html [accessed 2/3/2007].

Martin E (2007). “EPIDEMIOLOGY: Tropical Disease Follows Mosquitoes to Europe”. Science 317 (5844): 1485.

Charrel RN, de Lamballerie X, Raoult D. Chikungunya Outbreaks – The Globalization of Vectorborne Diseases. The New England Journal of Medicine. 2007;356(8):769-771.

Carey DE. Chikungunya and dengue: a case of mistaken identity?. Journal of the history of medicine and allied sciences. 1971;26(3):243-262.

Joint UKBTS/NIBSC Professional Advisory Committee.

Chikungunya Virus [online] 2006. Available from: http:// www.transfusionguidelines.org.uk/docs/pdfs/position_ statement_09_2006_07.pdf [accessed 2/3/2007].

Robinson M, Lumsden WHR. An epidemic of virus disease in Southern Province, Tanganyika Territory, in 1952-53. II. General description and epidemiology. Transactions of the Royal Society of Tropical Medicine and Hygiene. 1955;49(1):33-57.

Yergolkar PN, Tandale BV, Arankalle VA et al. Chikungunya outbreaks caused by African genotype, India. Emerging Infectious Diseases [serial on the Internet]. 2006;12(10). Available from: http://www. cdc.gov/ncidod/EID/vol12no10/06-0529.htm [accessed 2/3/2007].

International Committee on Taxonomy of Viruses. Chikungunya virus [online] 2006. Available from: http://www.ncbi.nlm.nih. gov/ICTVdb/ICTVdB/00.073.0.01.007.htm [accessed 2/3/2007].

Schuffenecker I, Iteman I, Michault A et al. Genome Microevolution of Chikungunya Viruses Causing the Indian Ocean Outbreak. PLoS Medicine. 2006;3(7):1-13.

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REVIEW

Is it time to put the lights out on sleeping sickness?

Camus Nimmo BA (Hons) Year 4 Medicine, University College London c.nimmo@ucl.ac.uk doi:10.4201.lsjm/gch.004

For the full article and references see thelsjm.co.uk.

Introduction Human African Trypanosomiasis (HAT), more commonly known as sleeping sickness, is classified as one of the world’s neglected tropical diseases (NTDs). The World Health Organisation (WHO) currently recognises 15 NTDs which until recently had received very little attention from both the world’s media and scientific communities.1 The incidence of HAT has followed a very interesting path. At the end of the colonial era in Africa (around 1960), the disease had been all but eradicated in most countries due to vigorous control policies put in place by the incumbent powers. However, following independence, new African governments had other priorities and many of these policies fell into disarray. By 1997, new cases had reached a peak of 35,000.2 This coincided with a recrudescence of international political interest in NTDs in general, and over the following 10 years the incidence has been more than halved to around 15,000 new cases in 2006 (Figure 1).3 With such a promising decline in cases, over the last 10 years, is it reasonable to hope that a further 10 years can see the complete elimination of the disease? And what lessons can we learn from HAT that apply to other infectious diseases worldwide?

About HAT HAT is caused by a single-celled protozoa from the Trypanosome genus. It is transmitted within human populations and between humans and animals by the tsetse fly vector. There are 2 major species affecting humans: Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense. The major features of each are summarised in Table 1. Both types have a significant impact on human health as well as an economic - caused by the infection of livestock. In the first stage of the disease the parasites infect the blood and lymph. In the second stage they cross the blood-brain barrier and affect the CNS. The treatment options for HAT are limited and old-fashioned. The options at each stage are shown in table 1.

Past Successes and Failures Almost complete control of HAT was achieved across Africa by 1960 by the previous colonial administrations. At the beginning of

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the 20th century this involved simple measures such as evacuating people from epidemic areas. By the middle of the century methods had advanced through using blood-based tsetse traps to spraying of dichlorodiphenyltrichloroethane (DDT) after its discovery during World War 2.4 Use of rigorous dedicated surveillance and control teams finally drove down the number of new cases to being virtually undetectable by the late 1960s. Post independence, most African countries did not see the dedicated HAT teams as worth continuing due to high running costs and the apparent elimination of the disease.4 Sadly, ensuing social upheavals over the next 40 years allowed further epidemics to occur, and infection to spread once more.

Current Successes Between 1995 and 2006, a leading factor in the falling incidence of HAT was the reduction in hostilities in countries that had suffered ongoing civil wars for long periods, particularly Democratic Republic Congo, Angola and Sudan. These changes have allowed WHO-sponsored programmes to develop in these countries over periods where they can begin to have an impact.3 There are significant differences between factors involved in control of gambiense and rhodesiense HAT. Gambiense is well controlled using tools targeted at infections in the human population, and most of the drop in HAT cases over the last 10 years has reflected a decrease in gambiense infection. However, rhodesiense HAT is less well controlled by these measures as it has a large animal reservoir as well. Between 1995 and 2006, there has been a 26% reduction in rhodesiense cases, but with an even larger increase in the interim. This compares with a 69% decrease in gambiense cases.3 Challenges for the Future Of the 36 countries classified as endemic for HAT, it had been eradicated or almost eradicated in 20 by 2006. An informal WHOsponsored meeting in 2007 involving representatives from these countries concluded that it was an eradicable disease.5 The way forward for eradication involves continuing increased surveillance and monitoring, which is best carried out using a combination of primary health care infrastructure and specialised teams.6

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REVIEW Diagnostic Techniques New diagnostic mechanisms are sorely needed to if the downward trend experienced over the last 10 years is to be maintained.

Diagnosis of gambiense relies on a blood spot card agglutination test, followed by microscopy to look for parasites. Diagnosis of rhodesiense is more challenging, as the card agglutination test does not work and relies on access to skilled staff and equipment, which may often not be available.

Neglect in Drug Development In terms of drug development, HAT suffers the same fate as other NTDs - an area of medicine which with far fewer drug advances than almost any other. The latest drug to be licensed for second stage gambiense HAT was eflorinthine 19 years ago involving multiple daily iv infusions, which carry a significant burden in terms of cost, infrastructure and availability.8 It is safer than melarsoprol which causes fatal encephalopathy in 10%9 and has regional pockets with substantial resistance. The advantage of melarsoprol is that it can be administered as a simple injection,8 and is still the only drug that can be used for second stage rhodesiense HAT. Clearly neither drug is ideal, and further research is needed. Unfortunately, there are no drugs currently being investigated after phase III clinical trials for pafuramidine maleate were stopped in 2008 following safety problems,10 after receiving over US$35m from the Bill and Melinda Gates Foundation.

The epidemiology of HAT is well understood, as shown by the effectiveness of simple control measures put in place initially over 50 years ago when political will was present. I see no reason why this should not be implementable in the future, and be able to lead to the control of HAT once more. However there is always a risk of return, it is important that research into HAT continues in the meantime.

The main challenges for the future are to develop better monitoring techniques so that cases can be easily identified. Hopefully the past will emphasise to us the importance that HAT does not suffer from the problems of its own success and be made a lower priority for funding and international effort.

References 1.

2.

3.

4.

5.

Vector Control Currently methods for control of the tsetse fly vector include aerial spraying of low concentrations of pesticide. This is rapidly effective but expensive and complicated to implement11. Selective spraying of insecticide onto animals on which tsetse flies feed is an effective alternative in settings where a smaller region is affected12. Potential strategies for the future involve further investigation of tsetse genomics to develop a genetically modified tsetse fly that is unable to carry Trypanosoma parasites13. However, this work is still many years off providing any practical interventions.

6.

Conclusion Looking at the graph showing incidence of HAT over the last 100 years makes astonishing viewing, emphasising the importance of understanding the interplay of epidemiology, medicine and politics when considering healthcare.

10.

7.

8.

9.

WHO List of Neglected Tropical Diseases [cited 2009 Mar 7].

Available from: http://www.who.int/neglected_diseases/diseases/en/ WHO Report on Global Surveillance of Epidemic-prone Infectious Diseases. p95-106. Available from: http:// www-tc.iaea.org/tcweb/abouttc/strategy/thematic/pdf/ presentations/tsetse_flies/WHO_Report_Diseases.pdf Weekly Epidemiological Record. 2006 Feb 24;81:69–80. de Raadt P. The History of Sleeping Sickness. Fourth International Cours on African Trypanosomoses, Tunis.

2005 Oct 11-28. Available from: http://www.who.int/ trypanosomiasis_african/country/history/en/index.html Report of a WHO Informal Consultation on Sustainable Control of Human African Trypanosomiasis [cited 2009 Mar 7]. Available from: http://whqlibdoc.who.int/ hq/2007/WHO_CDS_NTD_IDM_2007.6_eng.pdf Samarasekera U. Margaret Chan’s vision for WHO. Lancet 2007;369:1915-1916.

Deborggraeve S, Claes F, Laurent T, Mertens P, Leclipteux T, et al. Molecular dipstick test for diagnosis of Sleeping Sickness. J Clin Microbiol 2006;44:2884-2889.

Balasegaram M, Young H, Chappuis F, Priotto G, Raguenaud ME, Checchi F. Effectiveness of melarsoprol and eflornithine as first-line regimens for gambiense Sleeping Sickness in nine Médecins Sans Frontières programmes. Trans R Soc Trop Med Hyg. 2009 Mar;103(3):280-90 Blum J, Nkunku S, Burri C. Clinical description of encephalopathic syndromes and risk factors for their occurrence and outcome during melarsoprol treatment of human African trypanosomiasis. Trop Med Int Health 2001;6:390-400.

Press release: Immtech Focusing On New Infectious Disease Programs Following Discontinuation of Development of Pafuramidine. Released 2008 Feb 22 [cited 2009 Mar 7]. Available from: http://www. immtechpharma.com/documents/news_022208.pdf

Table 1: Features of gambiense and rhodesiense HAT T. b. rhodesiense

Geographical spread

West Africa

East/South Africa

% of all HAT cases

90

10

Disease specificity

Mainly humans

Humans and wild/ domestic animals

Time frame

Chronic

Acute

Acute symptoms (weeks to months)

Few

Swelling at bite site Occasional headaches Irregular fevers Pruritis Adenopathies

Chronic symptoms (months to years)

Severe headaches Sustained fever Sleep disorders Altered mental state

n/a

Drug treatment

Stage 1

Pentamidine

Suramin

Stage 2

Melarsoprol Eflornithine

Melarsoprol

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Figure 1: HAT cases reported annually 1937 - 2006

Number

T. b. gambiense

Year

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ARTICLE

A short introduction to the human papilloma virus and a consideration of the implications of global vaccination Polly Jordan BSc in Adult Nursing Year 2 Medicine, Barts and the London pollyredman@googlemail.com doi:10.4201.lsjm/gch.003

Cancer of the cervix is the second most common cancer among women worldwide, with an estimated 471,000 new cases (and 233,000 deaths) in the year 2000.1 Almost 80% of cases occur in developing countries, where in many regions it is the most common cancer among women and responsible for about 15% of all new cancers.2 Cervical cancer often affects younger women and the disease has significant emotional and financial cost implications.

For the full article and references see thelsjm.co.uk.

Source: Wellcome Images

Persistent infection with high-risk human papilloma virus (HPV) is the primary cause of cervical pre-cancer and cancer.3,4 HPV 16 and 18 are high risk types as they are most commonly linked with cervical cancer, although several other HPV types are also carcinogenic.5 HPV 6 and 11 are known as low-risk HPV types as they are uncommonly found in malignant lesions but are causative agents of ano-genital warts, recurrent respiratory papillomatosis, and in rare cases, have been associated with cancers of the larynx, vulva, penis and anus.6,7 Image: HPV in cervical epithelium

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Prophylactic HPV vaccines are now available for clinical use.

The two licensed vaccines are Cervarix (bivalent), which is active against HPV types 16 and 18, and Gardasil (quadrivalent) which is active against HPV 6, 11, 16 and 18. Meta-analysis shows HPV vaccine efficacy of both vaccines to be high, with significant reduction in the risk of infection from HPV16 and 18 in vaccinated cohorts.8 The question that now needs to be addressed is to whom the vaccine should be given to in order to gain maximum effect.

The current vaccines are projected to prevent 75-80% of cases of cervical cancer.4

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ARTICLE Cervical cancer is uncommon in countries with planned, population based screening programmes such as the UK and Norway, which have two of the most effective programmes in the world. However, cervical cancer is common in Eastern Europe and in developing countries due to insufficient cervical screening. This results in many patients presenting with advanced lesions at the time of diagnosis, as demonstrated by studies from Uganda.9 The highest impact of prophylactic vaccination would be observed in countries without screening programmes. Successful implementation in developing countries would depend on resource availability (the current cost of the vaccine is likely to be prohibitive) as well as overcoming significant obstacles such as conservative views on teen sexuality, lack of understanding regarding HPV, relatively low school attendance and geographical barriers to vaccine delivery.

Initial cost-benefit analyses of HPV vaccination suggest that vaccination of boys would not be cost-effective as prevalence would be low following comprehensive vaccination of girls.10 However, vaccination of males would boost ‘herd immunity’ through reducing the pool of disease. Additional benefits include protection against genital warts and some cancers of the perineum and anus. Homosexual men are a particularly high- risk group who would benefit. Gardasil is licensed for administration to both sexes and has been shown to provide close to 100% protection against genital warts.7 Further cost-benefit analyses would be required prior to the inclusion of boys in a comprehensive vaccination programme.

HPV vaccines have been shown to be effective in women who have never been infected with HPV16/18 and in those who have no current infection.11,12 For this reason, in the UK the target age group is pre-pubertal girls in order to vaccinate prior to the commencement of sexual activity.

Cost-effectiveness studies of the HPV vaccine are focused on countries in the developed world, many of which have established cervical screening programmes. For example in Ireland, base-case incremental cost-effectiveness ratio was found to be €17,383/ Life year gained, suggesting that vaccinating against HPV 16 and 18 would be cost-effective.13 A Canadian study concluded that vaccinating 12-year-old girls is likely to be cost-effective, with a significant reduction in cervical cancer mortality being observed.

Concurrent vaccination of 12-year-old girls with a cervical screening programme has also been found to be cost-effective in Germany, with 120 girls requiring vaccination to prevent 1 case of cervical cancer.15 In the UK, it is anticipated that there will be a 70% reduction in cases of cervical cancer and 400 lives per year saved following the introduction of the immunisation programme16. In terms of cost, Gardasil and Cervarix are both priced at £80.50 per vaccination, requiring a course of 3 injections over a six-month period1.7 A national immunisation programme for 12-year-old girls commenced in September 2008, at an estimated cost of £100 million per year18. A catch-up programme for 14-18 year-old girls is also scheduled at a cost of £200 million. A decision has yet to be made on the benefit of catch-up vaccination for women in the 18-25 year age group. The Joint Committee on Vaccination and Immunisation (JCVI) suggest that vaccinating this age group is not a cost-effective

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strategy but recognise that it could benefit some individuals.16 The national cervical screening programme is to continue in the UK at an estimated cost of £157 million per year.19 However, modifications to the existing programme are required in order for a national immunisation programme to be cost-effective.20 Modifications are likely to include increasing the age at which women first present for screening and increasing the screening interval.

The benefit to women in developing countries without established screening programmes or the resources available for effective treatment of premalignant and malignant disease of the cervix would surely be even greater. The difficulty lies in the cost of the immunisation programme and the infrastructure and compliance needed to deliver the course of the vaccine (3 vaccines over a 6 month period).

A cheaper alternative to a worldwide vaccination programme would be identifying and targeting sub-populations at high risk of infection. The difficulties of this strategy have been highlighted as there is no threshold number of risk factors that predicted HPV infection with sufficient specificity or sensitivity.21 In conclusion, evidence supports the vaccination of women across the world. A population based programme, rather than an opportunistic programme, would provide maximum effect. When the emotional and social benefits (e.g. reduction in working days lost) are included, the case for investing in HPV vaccination becomes even stronger.

References 1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

Parkin, D.M. Bray, F.I. Devesa, S.S. (2001) Cancer burden in the year 2000. The global picture. Eur J Cancer, 37(Suppl 8): S4-S66.

IARC (2005) IARC Handbooks of Cancer Prevention: Cervical Cancer Screening. Volume 10. Lyon: International Agency for Research on Cancer.

Wallboomers, J.M. Jacobs, M.V. Manos, M.M. et al. (1999) Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol, 189: 12-19.

Bulk, S. Berkhof, J. Bulkmans, N.W. Zielinski, G.D. Rozendaal, L. et al. (2006) Preferential risk of HPV16 for squamous cell carcinoma and of HPV18 for adenocarcinoma of the cervix compared to women with normal cytology in the Netherlands. British Journal of Cancer, 94(1): 171-175.

Pagliusi, S.R. Teresa, A.M. (2004) Efficacy and other milestones for human papillomavirus vaccine introduction. Vaccine, 23(5): 569-578.

Greer, C.E. Wheeler, C.M. Ladner, M.B. Beutner, K. Coyne, M.Y. Lang et al. (1995) Human papillomavirus (HPV) type distribution and serological response to HPV type 6 virus-like particles in patients with genital warts. J Clin Microbiol, 33(8): 2058-2063.

Lacey, C.J.N. Lowndes, C.M. Shah, K.V. (2006) Burden and management of non-cancerous HPV-related conditions: HPV 6/11 disease. Vaccine, 24(Suppl 3): S35-341.

La Torre, G. de Waure, C. Chiaradia, G. Mannocci, A. Ricciardi, W. (2007) HPV vaccine efficacy in preventing persistent cervical HPV infection: A systematic review and meta-analysis. Vaccine, 25(50): 8352-8358.

Makokha, T. (2007) Pilot study of human-papilloma-virus vaccine in Uganda. The Lancet Oncology, 8(5): 372-373.

Newall, A.T. Beutels, P. Wood, J.G. Edmunds, W.J. MacIntyre, C.R. (2007) Cost-effectiveness analyses of human papillomavirus vaccination. The Lancet Infectious Diseases, 7(4): 289-296.

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