Antimicrobials: the recalcitrant resistance

The WHO Collaborating Centre on Global Health Histories, which is supported by the Wellcome Trust, has produced a series of seminars in association with the WHO HQ, WHO Regional Offices, WHO Country Offices and national governments which look at the issue of antimicrobial (antibiotic) resistance, and why this remains such a difficult topic to tackle.

 

The seminars can be viewed and/or listened to here:

Global Health Histories Seminar 102: Strengthening Universal Health Coverage for the fight against Anti-Microbial Resistance

Location: Colombo, Sri Lanka

Speakers; Professor Sanjoy Bhattacharya, Director, Centre for Global Health Histories (CGHH), University of York; Dr Lakshmi Somatunga, Deputy Director-General, Medical Services(I), Ministry of Health, Sri Lanka; Dr Sunil De Alwis, Deputy Director-General, Education, Training & Research, Ministry of Health, Sri Lanka (Presented by Dr Dilantha Dharmagunawardena); Dr Suranga Dolamulla, Wellcome Trust Senior Research Fellow, University of York, Director of Tertiary care Services, Ministry of Health, Sri Lanka; Dr Kushlani Jayatilleke, Consultant Microbiologist, Sri Jayewardenapura General Hospital, Sri Lanka; Dr BVSH Beneragama, Deputy Director-General/ Laboratory Services, Ministry of Health, Sri Lanka; Dr Anil Jasinghe, Deputy Director-General, National Hospital of Sri Lanka

Global Health History Seminar 116: Antimicrobial Resistance

Location: Aarhus University, Denmark

Speakers: Dr Janis K. Lazdins Helds (formerly TDR/WHO, Coordinator Product Development and Evaluation for drugs, diagnostics and vaccines for neglected tropical diseases) and Professor Jens Seeberg (Dept. of Anthropology, Aarhus University)

Global Health Histories Seminar 137: Anti-microbial Resistance in South Asia: Challenges & Possibilities

Location: Jawaharlal Nehru University, Delhi, India

Speaker(s): Panellists: Professor Nandini Sharma (Maulana Azad Medical College, New Delhi), Dr Klara Tisocki (WHO South-East Asia Regional Office), Dr Suranga Dolamulla (University of York, UK and Ministry of Health, Sri Lanka), Dr Sirenda Vong, (WHO South-East Asia Regional Office)

 

 Global Health Histories Seminar 145: Antimicrobial Resistance (AMR) and Technological Challenges

Location: Colombo, Sri Lanka

Speaker(s): Dr B. V. S. H. Benaragama (Deputy Director-General, Laboratory Services and the National focal point for combating antimicrobial resistance, Ministry of Health, Sri Lanka), Professor Vajira H. W. Dissanayake (Chair and Professor of Anatomy, University of Colombo and Chairman, Commonwealth Centre for Digital Health), Dr Suranga Dolamulla (Wellcome Trust Senior Research Fellow, University of York and Ministry of Health, Sri Lanka)

 “The penicillin inventor, Fleming, warned in his 1945 Nobel lecture about penicillin resistance in future due to misuse and underuse. Within two years’ time, the first penicillin-resistant cases were identified,” says Dr Suranga Dolamulla, Wellcome Trust Senior Research Fellow at the University of York and Director of Tertiary Care Services for the Ministry of Health, Sri Lanka. Today, antimicrobial resistance (AMR) is recognised by the WHO as a threat on a level with climate change. “We have to think about AMR as a slowly-moving epidemic and treat it as an urgent and important issue. Otherwise, we might run out of time,” says Dr Klara Tisocki, formerly Regional Adviser, Essential Drugs and Medicines at the WHO South-East Asian Regional Office and now Team Lead (Pricing and Affordability),

Department of Health Products Policy and Standards, Medicines and Health Products, WHO. This whole scenario is really threatening our ability to treat common infectious diseases. It is resulting in prolonged illness, disability and death,” agrees Dr Lakshmi Somatunga of the Ministry of Health, Sri Lanka. It is also affecting animals and the environment.

And yet, like climate change, AMR is yet to be tackled effectively. It is more complex than simply telling practitioners or patients to stop overusing or misusing their medication. “Most people agree there is a problem but some have huge economic stakes invested in active denial of the facts; and political will to act locally is very slow to emerge in ways that mirror global power imbalances,” says Professor Jens Seeberg of Aarhus University (where he specialises in the field of anthropology of global health and antimicrobial resistance).

 

Access to and quality of antibiotics worldwide

Most of the global guidelines about antibiotic use and overuse originated from richer WHO members. In lower-income countries, the problem is more about access to medication, and the quality of that medication when it is available. “The key and most important thing that can be done is ensuring good-quality antibiotics, with a secure supply chain,” Tisocki says.

Dolamulla describes “two different scenarios of antibiotic production” for different parts of the world. “The developing world was really suffering without antibiotics and many actors, especially international organisations, supported antibiotic production for needy countries. But the technology transfer did not happen as expected. Sri Lanka was one of the countries that flagged this up with the WHO, wanting help to produce and prepare drugs in-country; other countries wanted a mix of imports and support.” Commercial pharmaceutical companies approached a number of countries, with the aim of moving into this market. “The Indian government was about to pay a very high amount of money as a royalty fee to a penicillin-producing company when one of the people conducting a WHO economic assessment mentioned that going ahead with a WHO-supported plant would be a good option for India rather than going ahead with the private firms. Even Sri Lanka did not get external organisational support for its antibiotics production plan, and had difficulties buying medicine from the world market because of the foreign currency exchange crisis.”

Today, antimicrobial use is strikingly different across the world. Tisocki outlines the WHO’s three categories [https://adoptaware.org/]: Access, Watch and Reserve. The Access category covers the antibiotics of choice for the 25 most common infections, which are recommended to be ‘available at all times, affordable and quality-assured’. “In a number of countries (Netherlands, Brazil etc) over 90 per cent of the antibiotics being used come from this list,” she explains. “In countries like Bangladesh, India and China it’s about 30 per cent.” About 40 per cent of the antibiotics used in those countries come instead from the Watch category, which are recommended ‘only for specific, limited indications’ and about 10 to 20 per cent from the ‘Reserve’ group, which the WHO states ‘should only be used as a last resort when all other antibiotics have failed’.

It’s also the case that many people, especially poorer people, access antibiotics without a prescription. Seeberg describes the way this happens in India. “Buying antibiotics over the counter from outlets that may or may not be formally registered is not an exception: it is common practice. Chemist shops function as de facto primary care practitioners and the booming Indian pharmaceutical industry pushes drug sales through any outlet, whether or not formal medical expertise is present. Antibiotics are everywhere and consumed for a wide range of ailments, only some of which may be attributed to some kind of bacterial infection. Everyday practitioners, with or without medical qualifications, receive visits of dozens of pharmaceutical sales agents who provide the only available kind of information about these drugs.” This is compounded, Seeberg adds, by the fact that many doctors also prescribe unnecessary drugs. “Quality can also be a big problem,” Tisocki adds. “If you have a sub-standard, poorly manufactured antibiotic which has only 60 per cent of the active ingredient, that’s most likely going to breed resistance. Anti-infectives and anti-parasitics are the most common in this category. It’s a big business; everyone buys a lot of antibiotics so criminals are very happy to move into it.”

 

The rise of AMR

Antimicrobials were initially hailed as a ‘magic bullet’ by the WHO when they were first introduced, with a programme with UNICEF in 1949. “Even then, though, people were aware of the potential risk and the possibility of resistance,” Dolamulla points out. Some diseases that were first tackled effectively, such as gonorrhoea, started to see a lapse in recovery rates. “In 1952 the WHO noted the proliferation of new drugs and potential AMR, and instructed members to take measures to prevent this.”

Dr Janis K Lazdins-Helds (formerly TDR/WHO, Coordinator Product Development and Evaluation for drugs, diagnostics and vaccines for the neglected tropical disease, and now an independent consultant) explains some of the complex mechanisms by which resistance develops. “It’s a natural phenomenon. Most antibiotics are derived from bacteria, and those bacteria develop mechanisms to protect themselves. So that is what's called ‘intrinsically related’ antimicrobial resistance: the natural defence mechanism.

“Then in clinical settings, there is ‘acquired’ resistance, where organisms lose their susceptibility to antimicrobials. They do so either because their own genes mutate, or because they acquire genetic material from other bacteria. This genetic information sometimes carries elements for different drugs, so a multi-resistant component comes in. The other aspect that is not usually highlighted is these things are both transmitted vertically, within a given species, and horizontally between different species.”

In addition, he adds, biocides (detergents) and heavy metals can also induce resistance. And resistance can be expressed in different ways. “Basically each antibiotic has a different mechanism of action or different target in the bacterial cell, and that target or that mechanism can be altered by the genetic information that the bacteria acquire.”

Moving on from the mechanism, he also explains the way AMR spreads. “In the human microbiome, our intestinal environment contains all kind of bacterial elements. These include some AMR components, but normally they do not proliferate. If you are submitted to antibiotic therapy you are changing the microbial environment in your gut, and then the bacteria with the resistance component have an advantage and start proliferating. Those bacteria then end up in the environment, are transmitted horizontally into other materials and enhance the pool of bacteria which have that form of AMR: and that again is acquired by humans. It can easily be carried from one environment to another. To illustrate this: if a healthy individual goes to a country where there's a high prevalence of antimicrobial resistance, they will probably be carrying these bacteria in their intestinal environment when they return home. Nothing will happen if they are not exposed to antibiotic treatment. But if they are, these bacteria will enhance.”

Lazdins sums up: “When addressing AMR you have to think about two things: First, the root determinants of antimicrobial resistance, which are basically determined by the microbiology of the process, the ecology of the microorganisms and the epidemiology (meaning how it’s acquired by the host and environment); and second, the morbidity and mortality that are the expression of AMR.”

 

AMR’s wide-ranging effects

This mix of unprescribed drugs, substandard medication, misuse and overuse has played a particularly huge role in the development of drug-resistant tuberculosis (TB), Seeberg points out. “Unless the market for antibiotics is regulated through a strengthening of the public sector and based on some kind of control with the marketing strategies of the pharmaceutical sector, this problem will continue. Controlling drug-resistant tuberculosis should be considered within the broader framework of controlling AMR.” This is especially urgent because there are two new drugs that are effective in tackling drug-resistant TB, and these may not remain effective if the wider issues of AMR are not addressed.

The effects of AMR do not stop with human beings. Farm animals are routinely fed antibiotics, often in large quantities. [https://www.who.int/news/item/07-11-2017-stop-using-antibiotics-in-healthy-animals-to-prevent-the-spread-of-antibiotic-resistance] “If you look at the bigger picture, 70 per cent of the production of antibiotics in the world goes to the animal sector, to protect them from infection. A lot of people in the agricultural sector prefer to give antibiotics before an infection happens. They are using antibiotics, not for the right reasons, and it is also one reason why AMR is on the rise,” says Dr Sirenda Vong, (WHO South East Asia Regional Office) There is also a severe effect on the environment because residual material and ingredients can percolate into the water during the manufacturing process and then be discharged into the surroundings.

 

Shaping international opposition to AMR

As Dolamulla flags up, this issue has been a concern for many years now; and the WHO first passed resolutions about it in 1998. “We have 20 years of this, addressing policies, but what is interesting from the perspective of history is the context in which these things have been put across, over the years.” The first resolution focused on issues like education, research and control. In the next few years, the emphasis shifted to containment, within the context of health security and epidemic alerts. In 2007 the attention was on the rational use of medicines. Seven years later, the focus returned to the original one. The resulting 2015 WHO global action plan [https://www.who.int/antimicrobial-resistance/global-action-plan/en/] has five strategic objectives: improving awareness and understanding; strengthening knowledge through surveillance and research; reducing the incidence of infection; optimising the use of antimicrobials; and developing a comprehensive case for sustainable investment. “This is very similar to what was said back in 1998,” Dolamulla says.

At the same time, there is an important historical context which has to be taken into account. Professor Sanjoy Bhattacharya, Director of the Centre for Global Health Histories (CGHH), University of York has looked at the earlier history of the drugs – the point at which antimicrobials were being hailed as a ‘magic bullet’, despite reservations – and made some surprising findings. “What is very striking is that initially, the WHO didn’t have any essential lists of medicines. If you follow the money in relation to these lists, what you find out is stunning; and it’s something that historians have ignored till now. In the 1950s and 1960s, it was countries like India and Ceylon/Sri Lanka which were actually funding the development of new departments within the WHO headquarters and the WHO regional office. It was Asian money – not American or Western European money –  which was creating changes within the WHO although it wasn’t politic for anyone on either side to talk about this.”

Bhattacharya explains why this particularly important when it comes to combating AMR. “There was wide-ranging political support within South-East Asia not only for creating the creating essential lists but also for introducing antibiotics into that list for all sorts of treatments. Medication including antibiotics was seen as a right and a mark of equity.”

 

The need for information and surveillance

There is also another sticking-point when it comes to defeating AMR resistance: the need to know exactly what is being used where, in a field where much consumption is simply unmonitored. Vong sums it up. “Surveillance is essential because you need to show the data to see where you are, and in order for countries to advocate for more funding and resources to combat AMR. How do you sell that idea of the rise of antibiotics to the public, or to other professionals, when you don’t know how many people are dying of it and you don’t have that data? We come up with something about microbiology, but how many people understand that concept? It’s easy to talk about raising awareness but how you do it is more complex.” It’s also necessary to collate this information across different countries and sectors, covering the use in all fields. “This is a global issue. The [WHO] global AMR surveillance system is essentially an IT platform to collect all data across the world. We want to measure trends, and to know if the data we have is accurate. We also want to measure the use of antibiotics and establish whether reducing antibiotic use or using antibiotics better has an impact on AMR.”

However, at the moment, Vong explains, that data simply isn’t available. “There is some from the US, Europe and Thailand. But when you come to a country like India or Sri Lanka and ask for data on AMR, where do you start? The level of resistance to one particular antibiotic?” This is compounded even further by the specific nature of the data that’s needed. “AMR surveillance data is complex to collect and to analyse. How many bacteria are we dealing with? How many antibiotics are we dealing with? And what type of infection are we dealing with – is it blood, is it urinary, is it respiratory? Analysing one dosage against another is very complex.”

 

Ways forward

Some specialists are exploring ways to make antibiotic use much more customised, through gene sequencing, and give patients exactly the appropriate treatment. “The conventional culture techniques will help us pick up that dominant organism but it doesn’t give the bigger picture of the surrounding colony of microorganisms; so you kill the dominant organism but the ulcer continues. You try other antibiotics and so on, and this goes on and on. This kind of thing actually contributes to perpetuating the scourge of AMR,” explains Professor Vajira H.W. Dissanayake, Professor of Anatomy and Genetics, Faculty of Medicine, University of Colombo, Immediate Past President Commonwealth Medical Association, and Chairman, Commonwealth Centre for Digital Health'. “Alternatively, you can completely customise different ways of treating the patient. You completely analyse the microbiome and do the bioinformatics analysis which gives you the entire drug-resistance pattern. So you’ve got your set of organisms which are based on the sequence, you identify what is resistant to what and then you can also determine which drug to give which patient.” Others are starting to look at how the resistance could be reduced within a drug that has become ineffective, by eliminating or silencing the genetic element which has made this happen. 

Much of the current focus is on finding new drugs to replace ones that are now becoming ineffective. But for one thing, that does not tackle the problem of AMR in itself: it just shifts it into the future. In any case, drug development on this front is not going ahead as fast as it might be. “Not only are large pharmaceutical companies reluctant to take forward innovative molecules/approaches: more concerningly, they are exiting antibiotic research altogether,” says Lazdins “This is partly because the drugs they do develop would not necessarily be used, Dolamulla adds. “We are asking them to produce new antibiotics exactly to attack resistant organisms. The US Centers for Disease Control (CDC) has said something very remarkable: that this antibiotic stewardship is good for public health but the production of new antibiotics is not good for drug companies as there is a long lead time (20 years) and low return on the initial investment. So basically it’s not the best from a business perspective.”

 But it is also important to see AMR in its wider context. Bhattacharya points to the history he has uncovered, and what it suggests for present-day policies and practices. “Just issuing technocratic advice about rationality and its use is not enough. If you are going to limit the use of antibiotics you have to engage with society and political actors and explain why this is a need and not a denial of rights.”

 

Radhika Holmström is a Wellcome Trust-funded writer and communications specialist working with the WHO Global Health Histories project at the University of York.

Vaccination Opposition

The WHO Collaborating Centre on Global Health Histories, which is supported by the Wellcome Trust, has produced a series of seminars in association with the WHO HQ, WHO Regional Offices, WHO Country Offices and national governments, which look at the reasons why a growing number of people are not taking up vaccinations – and how this can be countered. 

 

The seminars can be viewed and/or listened to here: 

Global Health Histories Seminar 107: Cultural contexts of health: vaccine hesitancy - Why do some people not vaccinate?,  WHO Regional Office for Europe, Copenhagen, Denmark

Speakers: Heidi Larson (London School of Hygiene & Tropical Medicine), Robb Butler (WHO Regional Office for Europe)

 

Global Health Histories Seminar 113: Immunization for Universal Health Coverage, Nazarbayev University, Kazakhstan

Speakers; Professor Clare Griffin (School of Humanities and Social Sciences, Nazarbayev University), Dr Byron Crape, Nazarbayev University, Dr Namrata Ganneri (University of York and SNDT College of Arts & SCB College of Commerce and Science for Women, Mumbai).

 

Global Health Histories Seminar 133: The Health Challenges of Social Marginalisation, Timisoara Science Festival, Romania

Speakers: Vlad Mixich (Executive Director of the Romanian Health Observatory and Board Member of the European Public Health Alliance); Lynda Dunlop (Lecturer in the Department of Education at the University of York) Oana Romocea (Executive Director, Hategan Foundation & Founder of the Timisoara Science Festival) and Ruxandra Eva Ciucur (Partner at Hategan Attorneys)

 

This briefing draws upon the presentations at these seminars.

 

In 2020, the hope of a vaccine to target COVID-19 has become a major global focus. Yet there remains a significant minority of people who are not sure if they would accept vaccination – and a number who would flat-out refuse it.

 

“Vaccination is very important. Without it, we wouldn’t have achieved the eradication of smallpox,” says Professor Sanjoy Bhattacharya, director of the Centre for Global Health Histories at the University of York and of the WHO Collaborating Centre for Global Health Histories. Other diseases have been minimised to the point where family doctors often never come across them, and babies in many countries are immunised routinely and repeatedly from the age of a few weeks. Yet the opposition to a COVID-19 vaccine is only part of a greater phenomenon.

 

Opposition to vaccination, or ‘vaccine hesitancy’, is actually increasing in the 21st century. A relatively small number of people are adamantly opposed to all vaccines but a growing number, particularly parents of young children, are sceptical about vaccination or about specific vaccines. “In contrast to the great successes of the 20th century, there have been well-publicised problems with immunisation in the 21st century,” Dr Clare Griffin of Nazarbayev University points out. “The history of vaccination and immunisation is not a march of progress but actually more like a bell curve.” 

 

“The World Health Organization (WHO) estimates that the measles vaccine saved an estimated 17.1 million lives between 2000 and 2015 alone,” says Dr Byron Crape of Nazarbayev University. By contrast, children who have not been vaccinated have been subject to successive outbreaks of measles, pertussis and other diseases, some of which have had serious effects including fatalities. “Every time we have an effective antivaccination movement we see a decline in vaccinations and an increase in the diseases those vaccinations were designed to protect against,” Crape adds.

 

What is fuelling this vaccine hesitancy and the resulting rise in entirely preventable diseases?

 

A movement with a long history

Although the anti-vaccination movement has gained particular traction in recent years, it has been around as long as vaccination itself. “The notion that vaccination is a delusion goes way back, from the moment the whole concepts of vaccination and immunisation were being configured,” says Professor Heidi Larson of the London School of Hygiene & Tropical Medicine, who is also the director of The Vaccine Confidence Project. 

 

The arguments against vaccination have always invoked concepts of ‘purity’ and ‘nature’. “The idea that ‘anything that's natural is better than a vaccine’: that's been around since day one.” And it has, today, become big business too, she adds. “A lot of the naturopathy and homoeopathy books, videos and businesses are making a lot of money promoting their products over-vaccination.” Alongside that, Larson points out, people do not like the idea that vaccination is being imposed on them and/or their children. “The first anti-vaccination leagues were actually initially anti compulsory vaccination.” 

 

The paradox of low-level disease rates

Ironically, the very fact that many diseases are now seen much less frequently has contributed to the drop-in vaccination rates. “When there was a spike in smallpox rates, people got scared and were vaccinated: when rates dropped, demand reduced,” says Bhattacharya. If that is the case with a lethal, much-feared disease it is hardly surprising that it’s the same with other conditions. “If you’ve never seen a vaccine-preventable disease in your community you are less likely to be concerned about that disease. You become complacent and apathy sets in. I'm sure that if I went to my mother's home community on the Isle of Man and I asked people about measles today, half of that community would probably tell me that measles was eliminated decades ago,” says Robb Butler, then WHO 

Programme Manager, Vaccine-preventable Diseases and Immunization and now Executive Director, WHO Regional Office for Europe. “Particularly if you’ve got a concern about vaccination – even if it’s only a very small concern – if you don’t feel you need it, why would you do it?” 

 

That complacency can extend to health policy as a whole, Butler adds. “Fewer and fewer new GPs know what a case of rubella or measles actually looks like. Particularly in countries that have not been witnessed or suffered the phenomenal health and financial costs of an explosively large outbreak, there’s less likely to be sufficient investment in that element of the health programme.”  

 

Dr Vlad Mixich, executive director of the Romanian Health Observatory, explains how measles vaccination rates have dropped dramatically in Romania over the past 20 years – a sharper decrease than anywhere else in the world – and how rates have increased as a result. “We started from a pretty good coverage, but we’re now very low according to WHO standards and well below the level recommended for herd immunity. That led to an outbreak of measles between 2016 and 2019, with more than 17,000 reported cases. There were also 64 deaths, all except one in unvaccinated children.”

 

Justified fears

Historically, there have been plenty of situations where opposition to being vaccinated is extremely easy to understand. “We have to be careful when we identify resistance or hesitancy, to what people are resistant about,” Bhattacharya says. He gives several examples in the context of the smallpox vaccine in India in the 1960s. “The rotary lancet equipment which was initially used for smallpox vaccination effectively inflicted an open wound which could become infected. The resistance in rural India was not to the vaccine itself but to the sepsis which could result from the vaccination process.”

 

Later on, in the 1970s, vaccinating teams were feared for other reasons. “There was the occasion where 100 volunteers were trained to go into the villages of Uttar Pradesh. As it turned out all 100 were Hindu. They tried to vaccinate in Muslim-dominated villages, and they realised everyone had disappeared. This was also at the time when young Muslim men were being forcibly sterilised, and the later enquiry revealed that this was why they had run away. So very quickly international aid agencies learned that they needed to get a range of local collaborators, who could inform them about fears, and anger, and then slowly involve local vaccinators.”

 

There were some even more frightening incidents too. “International volunteers recruited to the Indian smallpox eradication programme were often heavily-built overseas workers over six feet tall. Their job was to hunt down people resisting vaccination, sit on them and forcibly vaccinate them. This is not a figment of my imagination; I actually interviewed the people who did the sitting and are now very guilty about having sat on emaciated bodies. And those emaciated bodies that were sat on so disrespectfully, those women who felt that their dignity had been compromised as they were sat on by a man, and their sari covering their faces was possibly moved, are now the bodies of grandmothers. They are some of the most influential decision-makers about vaccination out there.”

 

Larson has further examples of what she terms “the surrounding histories and politics that play out on vaccinations”. “We’ve seen multiple mass reactions to the HPV vaccine which have been deemed psychosomatic or anxiety-related in a number of settings. One very widely publicised case was in Colombia, where some of the girls were having cases of tachycardia, shortness of breath, chest pain and fainting. This was in an area with a history of paramilitary violence and sexual violence against young women. The experience of the vaccination triggered and released those deep anxieties and fears; and right now, if you go to any of the global registries, HPV has the absolute highest number of adverse events reported (not confirmed) following immunisation. There are a lot of reasons these anxieties are coming out – often unrelated to the vaccine itself, but triggered by the experience of vaccination.”

 

Parents’ concerns about vaccination

Even in ‘normal’ contemporary urban situations, vaccinating children, particularly new babies, can be a very upsetting experience. It involves, after all, putting a needle into a child and causing them pain. Particularly since this involves making an appointment, taking time off work, and possibly sorting quite a few other logistics too, it’s easy to see how hesitancy can tip over into reluctance, and then into avoidance without thinking through the genuine risk to a child who is not vaccinated. But importantly, Larson does not feel that vaccine hesitancy should simply be overruled. 

 

“We can't prevent vaccine hesitancy, and nor should we,” she says. “I mean, think about the whole process of smallpox variolation from the beginning: you take some virus from a cow and you put it in a child. That can’t be something nobody questions. Any responsible parent with a first-time child should be asking questions about what they're giving their child, whether it's a medicine or a vaccine or anything. So, the last thing we should be doing is shutting them up. In fact, that’s one of the biggest reasons we're having the challenges we face right now; I think it’s payback time for the years of ‘take this, it's good for you, it's totally safe, don't worry about it’.” 

 

In fact, Butler argues, many parents who do vaccinate are not particularly thinking their decision through either. “A lot of people vaccinate without thinking about it. Their decisions are neither well-informed nor poorly-informed; they are just doing it because of social copying.” “It’s very interesting that in Romania, the most vaccine-hesitant people are the ones who are highly educated and urban,” adds Mixich. Butler’s own experience echoes this too. “It’s truly remarkable, but there is a lot of vaccine hesitancy in families from higher socioeconomic groups where both parents work, particularly in northern Europe. The most fortunate often make the most unfortunate decisions. My own GP told me I’m in the hard-to-reach population. My wife and I both work, we don’t have a particularly cohesive relationship with our local community and we don’t go to church – so we become hard for health services to reach.”

 

But clearly, respecting this hesitancy does not mean accepting vaccine refusal. Instead, it’s important to analyse just what is going on, and particularly how vaccination hesitancy is able to spread at the moment; and, as a result, work out how it can be combated.

 

Trust and lack of trust

Larson argues very strongly that effective vaccination coverage only happens if people trust what is on offer. “Trust is about a relationship. Do we trust that someone is capable of doing what they say they can? And what is their motive? ”"Is this doctor genuinely concerned about the health of my child and my family, or is he/she in it for the money they make out of it?” some parents ask.

 

They need to trust the product, the healthcare system and the political system. Romania provides a very good example of a society where this is not the case, with inevitable results. “There is very low trust in the whole political infrastructure, including its institutions,” Mixich explains. “And the trust in the healthcare system is also extremely low, although we do place a reasonable amount of trust in scientists. A recent study also showed that Romanian parents, whether they’re vaccine-hesitant or not, have strong concerns about conflicts of interest and financial interest when it comes to doctors and the pharmaceutical industry.”

 

There’s an obvious further breakdown in trust if healthcare workers themselves express concern about the vaccine, as, for instance, a high proportion in Romania do. “There are a number of physicians in Armenia who actually state that they refused to vaccinate their children against anything except polio,” adds Crape. “They know the history of polio and what polio does, but they don't recognise the importance of vaccinations against all these other childhood diseases.” Overall, Larson sums this up as “one of the biggest challenges we have now. We have this whole cohort of health professionals including scientists and Nobel Prize winners who are questioning one or more vaccines”. 

 

 

The internet and fake news

The huge difference for the anti-vaccination movement and vaccine hesitancy has, of course, been the internet. In the past two decades, the way people consume, create and relay news has changed completely, with increasing numbers relying solely on what they find online – especially for health information. It is also, importantly, a worldwide change; people in extremely remote areas have access to the internet and all it contains – and the technology and platforms are also changing very rapidly.

 

The information online includes rigorous, peer-reviewed studies and meta-studies into different forms of immunisation. It also includes misinformation, misinterpretation and anecdotes presented as disinterested research – complete with pictures and video to give the messages extra punch. Crape cites examples in a range of different languages. “There’s a picture of crying baby and an ugly needle – it’s an emotionally laden photograph – alongside six reasons to say no to the vaccine. They’ll say that pharmaceutical companies can’t ever be trusted; that all vaccines are loaded with chemicals and heavy metals (in reality there are no heavy metals in the current children’s vaccines); and so on. Yes, a handful of vaccines have been removed from the market but those are very few and the ones that are currently provided are safe. And they say, ‘you can always get vaccinated, but you can never undo a vaccination’, to suggest that you still have the choice even if you don’t do it.” 

 

Crape adds: “This is all underpinned by bad or incomplete science or findings that are taken out of context. If you look at the peer-reviewed published literature, you can’t find evidence for the claims that rates of learning disabilities, or attention deficit hyperactivity disorder (ADHD) or autism are higher in children who have had the vaccines. And then finally they try to justify it further by showing books that show the dangers of vaccines, all of which are written by physicians, in order to show that this is real science, it’s a very serious problem and we're killing our children with vaccines. It doesn’t matter where you live: all you have to is pull out your phone and hook up to Google and they're all there for you. The anti-vaccination movement is spreading out from high-income countries and those countries haven’t responded sufficiently.” 

 

Public health campaigns and professional responses

Others agree that public health campaigns to date have not tended to dent the success of the anti-vaccination ones. “From a public health authority perspective there's not enough done in terms of understanding and managing Dr Google,” says Butler. “In Europe, reliable robust information that’s simply easy to use information usually comes at around 15th place on a search. I feel there’s not been enough done on it, but it’s also extremely difficult to tackle because a health authority can never be as nimble as a vocal single individual.”  

 

He adds: “As human beings, we’re guided by emotion, and we have a simplification bias. We find that when information and actions are easy to understand we're more likely to change our perceptions and behaviours accordingly. The anti-vaccine lobby understands this very well – and to some extent so do pro-vaccination campaigns, with examples like children blinded by rubella, so parents are often left with very mixed messages.” And most people decide in advance which stories they are going to believe, too. “We have a confirmation bias; we're more likely to believe messages that support the conclusions that we've already come to, and we filter new information according to this.” 

 

Dr Lynda Dunlop, Lecturer in the Department of Education at the University of York, adds a further perspective. “According to the WHO, around half the adults around Europe have poor health literacy. This goes right back to the classroom and how young people learn about science and health. We need better collaboration with teachers, research-informed resources, and support from other disciplines – and we need to pay attention to the values and attitudes that young people bring to the classroom in the first place.”

 

Larson also picks up the issue of how individual health professionals are not equipped to counter vaccine-hesitant patients or parents. “There’s usually very little in medical training about vaccines. You’re taught about giving a difficult diagnosis, but not about how to handle a conversation where someone says ‘I don’t want what you think I should have’ or start challenging you, which is happening more and more. Very often health professionals just shut down and say ‘That’s OK, you don’t have to have the vaccine’, in order to keep the trust of the patient. So, some groups are suggesting that training in dealing with that sort of conversation would be useful.”

 

Stories and narratives

Mixich frames this in terms of narratives and stories. “We are impressed by stories, regardless of how truthful those are or how well-prepared we are to appreciate them. They can be a good tool or a very dangerous one.” The anti-vaccination stories are often very coherent, moving and aimed at getting an emotional response: they are not concerned with the qualifications or nuances of factual reporting, because they operate on a different level. They also focus heavily on temporal associations – events that happen after vaccination but aren’t necessarily anything to do with the effects of vaccination.

 

“We are slowly understanding how to communicate better,” says Butler. “We’re realising that it’s not enough to ‘myth-bust’; we now know that it's very important that we replace that myth with information. And the way we frame our arguments and facts is very important as well, which unfortunately many healthcare practitioners in the European region still don't understand. You’re much more likely to opt for a burger that is 75 per cent fat-free, or a vaccine that is 99.9 per cent safe, than one that’s communicated to you in a different way.”

 

His feeling, though, is that vaccine hesitancy cannot be solved by communications alone. “Communications have a phenomenal amount to do with it, but we know from the last four decades of communicable disease prevention that knowledge doesn't necessarily predict action. An informed individual is not necessarily a behavioural responsive or responsible one. I think we need to embrace the social sciences, and people from medical humanities and medical anthropology backgrounds, to get their insights into hesitancy and what we need to do to tackle it. The solutions are as much to do with tailoring service provision as they are with communicating messages.”

 

“The end message is that evidence-based information isn’t enough any more,” Mixich concludes. “In countries like Romania, it’s very important for us to know that a safe and effective vaccine has two ingredients: good science and good stories.”

 

 

Radhika Holmström is a Wellcome Trust-funded writer and communications specialist working with the WHO Global Health Histories project at the University of York. 

 

Eradicating Polio

The WHO Collaborating Centre for Global Health Histories, supported by the Wellcome Trust, has produced a series of seminars in association with the WHO HQ, WHO Regional Offices, WHO Country Offices and national governments.  

One seminar, shown at a major WHO EURO event, focuses on the move towards world eradication of poliomyelitis and why this has still not been achieved, 20 years after the originally stated goal of 2000.

 

The seminar can be viewed and/or listened to here:

Global Health Histories Seminar 110: Polio, immunization and universal health coverage, University of York

Speaker(s): Thomas Abraham (Director, Public Health Communication Programme, Journalism and Media Studies Centre, the University of Hong Kong) and David Heymann (London School of Hygiene and Tropical Medicine, and Head of the Centre on Global Health Security at Chatham House & formerly WHO Assistant Director-General)

 

 

This briefing draws on the presentations at that seminar.

 

On 25 August 2020, the Africa Regional Certification Commission certified the WHO African Region as wild polio-free, after four years with no cases of wild poliomyelitis (polio) in the region. Over 90 per cent of the world’s population is now free of wild poliovirus, and only 33 cases were reported in 2018. However, Africa still faces the challenge of vaccine-derived polio, which as of October 2020 was present in 14 countries of the region.

 

Many people consider that polio eradication would constitute a major advance. There are three strains of wild poliovirus, each of which requires a specific vaccine to be eradicated and all of which cause paralysis. The disease mainly affects children, with roughly one in 200 wild poliovirus infections leading to irreversible paralysis. This is most often in the legs, but the brain and/or the breathing muscles can also be affected. At the same time, the majority of infected children are asymptomatic. “Whereas smallpox, for instance, is very easy to identify because it leaves pockmarks all over the body, for every child who is paralysed by polio there are 600 to 1,000 children who are infected and can transmit the disease to others but who show no signs whatsoever,” explains David Heymann (Professor of Infectious Disease Epidemiology at the London School of Hygiene and Tropical Medicine, head of the Centre on Global Health Security at Chatham House and formerly WHO Assistant Director-General, with responsibility for polio eradication).  

 

In 1988, the World Health Assembly (WHA) passed a resolution to eradicate polio globally by 2000, describing this as ‘an appropriate gift … from the twentieth to the twenty-first century’. Type 2 was eradicated in 1999 and no case of type 3 has been found since the last reported case in Nigeria in November 2012. However, more than 20 years after the start of this century there is still endemic transmission of type 1 wild poliovirus in border areas of Afghanistan and Pakistan, and the WHO estimates that failing to eradicate polio from these areas could mean that polio spreads again, causing up to 200,000 new cases a year worldwide within 10 years.

 

“The polio programme itself is, as ever, optimistic. The message is that the incidence of polio has been reduced by 99 per cent from the time the programme was launched, and that is absolutely true,” says Thomas Abraham (Director, Public Health Communication Programme, Journalism and Media Studies Centre, the University of Hong Kong and author of Polio: The Odyssey of Eradication. “But in two countries it has not been interrupted, and at the same time vaccine-derived polio cases are repeatedly popping up in areas that were once thought to be polio-free.”

 

 

A sudden WHO priority

Abraham is particularly interested in how the decision by the WHA to eradicate the disease came about in. “On one level it's as clear as daylight: 1988 the World Health Assembly voted to try and eradicate polio by the year 2000, at another level it is really mysterious.”

 

The proposal to eradicate was made by WHO Director-General Dr Halfdan Mahler, only three weeks before his departure from the post, in a speech to the World Health Assembly in1988. The occasion was the 40th anniversary year of the WHO and the 10th anniversary of the declaration from the Alma-Ata International Conference on Primary Health Care, which had expressed ‘the need for urgent national and international action to protect and promote the health of all’.

 

However, Abraham points out, this was a quite surprising focus for Mahler, who had said publicly and repeatedly that the smallpox eradication programme was the last single-disease eradication programme to which the WHO would commit its resources. “His philosophy was completely different; that same money, he felt, was much better spent by building up health systems, especially at the village level. He firmly believed that the decision on which diseases ought to be tackled first was something that really should be determined at the levels of communities and not by big organisations sitting in Geneva or New York. For him, eradication programmes represented everything that was wrong with healthcare.” 

 

Yet suddenly, Mahler made a quite unexpected public commitment to eradicating polio within the next 12 years. “It was not even on the agenda initially. One of the most consequential decisions that the World Health Organization has taken was actually done pretty hastily – and it was also a really low-key resolution, saying that countries were ‘invited to formulate and consider plans for vaccination coverage in order to make this happen’. “There’s no paper trail to explain how this change happened, and the decision was hastily taken” This was in sharp contrast to the activity that preceded (and indeed succeeded) the resolution to eradicate smallpox.” 

 

Heymann offers another reason for Mahler’s change of mind. The Global Polio Eradication Initiative is a public-private partnership led by national governments with six-core partners – the WHO, Rotary International, the US Centers for Disease Control and Prevention, UNICEF, the Bill & Melinda Gates Foundation and Gavi, the Vaccine Alliance. Rotary International has been a particular driver in this. “Some of the Rotary groups from the US went to the Philippines back in the mid-1980s on an exchange programme, where they saw children paralysed from polio which had been gone from the US for almost 20 years. They became great advocates for getting rid of polio – they actually went over and helped in the vaccination programmes – and it was Rotary International which really pulled together a partnership with UNICEF, the WHO and the Center for Disease Control to tackle it. I would think it was Rotary that convinced Mahler that this was an important thing to do.” 

 

Immunisation and wider strategies

The polio eradication programme was linked to the WHO’s wider immunisation programme, which aimed to ensure that by 1990 every child would be immunised against diphtheria, pertussis (whooping cough) and tetanus. “The resolution said it should be pursued in ways to strengthen this integrated immunisation programme,” Heymann explains. “Polio was meant to be the sail if you like, and the wind hitting these sails would push the entire boat to shore,” Abraham adds. It was also an easy vaccine to deliver (unlike, for instance, smallpox vaccine) because it was given in oral drops and did not require trained health care workers to immunise children.

 

However, at the start of the programme access to polio vaccine varied hugely. In some richer countries it was offered routinely to children; conversely, in a number of WHO regions (Africa, the eastern Mediterranean and Southeast Asia) polio immunisation rates were far too low to produce herd immunity (which requires around 90 to 95 per cent immunisation). In addition to routine immunisation, the programme supported national immunisation campaigns to increase coverage. 

 

The other strategy in the eradication programme was a highly sophisticated surveillance programme using cutting-edge technology. A network of national and regional laboratories around the world took poliovirus isolated from stool specimens – including specimens taken from the Mumbai sewers – analysed them using genetic sequencing and stored the results in a shared global database. “That sequencing is very important because the poliovirus mutates at a steady rate as it transmits through humans and each type has many sub-families as a result,” says Heymann. “Genetic analysis means it’s easy not only to see what those mutations are but to trace back to see where the virus might have originated. For instance, in Pakistan they were actually able to find cases of polio in 2010 that could be linked back to cases in 2009 genetically; and that meant it was possible to go back to the place where this virus was thought to originate and make sure that it had indeed been eliminated from that area.”

 

Vaccine-derived polio

There is a further issue in that the oral form of polio vaccine contains a weakened form of the live poliovirus, which is excreted from the body. In places which do not have adequate sanitation this virus can spread to other people, and in areas where there is not a high enough immunity in the local population, the virus circulates and can mutate into a new active strain: a circulating vaccine-derived virus (cVDPV). 

 

As a result, in addition to the wild poliovirus still in circulation, cVDPV has become a major stumbling-block in the journey towards eradicating the disease. “In fact, now cases of vaccine-derived polio are greater than the number of wild polioviruses,” Abraham points out. “I think this is really worrying.”

Vaccination opposition

However, many vaccines have met with considerable opposition and polio is no exception. In 2003 wild polio had been absent from the state of Kano in northern Nigeria for four years when the state governor announced that he had read online that the vaccine made young girls sterile. “He saw this as a plot being run through the UN agencies which were controlled by Western countries,” says Heymann. “As a result, polio spread from Nigeria all the way across into Indonesia, through trade and religious pilgrimage groups. So, countries that had been polio-free became infected again. It was very hard to get polio activities restarted in northern Nigeria.”

 

Two laboratories, based in South Africa and India, which worked with the WHO – but crucially were not part of the WHO, as the WHO was considered part of the problem – offered to test the vaccine for the government of Nigeria. Their results showed no impurities which might cause sterility, but the Nigerian national vaccine expert group refused to accept this. A resolution from the Organisation of the Islamic Conference (now the Organisation of Islamic Cooperation), high-profile vaccinations and requirements from Saudi Arabia that all pilgrims entering the country were vaccinated all failed to change the governor’s views. Finally, a resolution from the WHO in 2008 and the subsequent pressure from within Nigeria did push him to rescind his views, but vaccine refusal continued for some time. 

Priorities, context and the future

Abraham also highlights another problem; that for many people, polio simply isn’t as important a priority as other conditions. He cites a man he met in northern Nigeria, who agreed to have his children vaccinated against polio. “Then he burst out later saying: ‘Polio, polio, polio. Why polio? When my child has a fever, the nearest public health centre is 10 kilometres down the road; I need to go to the main road and find a lift or a bus or get someone to take me there. When I get there, there are no medicines. But people are coming here every day and pressing polio drops on me.’ Children are dying of other things – malaria, measles, diarrheal diseases. These are the real killers, for many people, but they just see all the emphasis on polio, and it doesn’t make sense to them.”

 

Despite this, however, wild polio is nearly eradicated. Heymann flags up final concerns. “Strong leadership and innovation have been instrumental in stopping wild poliovirus. Countries have successfully coordinated their efforts to overcome major challenges such as high levels of population movement, conflict and insecurity restricting access to health services, and the virus’s ability to spread quickly and travel across borders. But the polio endgame has been slowed by vaccine-derived polio; we now have a world where vaccine-derived polio is equally as important as wild poliovirus.” 

 

What’s more, there is a considerable amount of the virus – both wild and polio-derived – either taken from the vaccine or from stool samples, which is still stored in laboratories around the world. “And there is one last sobering issue about polio eradication,” Heymann concludes. “Even after wild poliovirus is gone and vaccine-derived poliovirus is gone and all the poliovirus in these laboratories has been locked up or destroyed there will still be a risk because the poliovirus has actually been synthesised in a laboratory way back in 1991, just using the genetic sequence. It will still be possible to construct a new poliovirus. So, polio has had many challenges: and the final challenge is both when will eradication finally be completed and whether the disease will remain permanently eradicated.” 

 

Radhika Holmström is a Wellcome Trust-funded writer and communications specialist working with the WHO Global Health Histories project at the University of York. 

 

 

 

 

 

 

 

 

 

 

 

 

Panic and pandemic: learning from history

The WHO Collaborating Centre on Global Health Histories, which is supported by the Wellcome Trust produced a seminar in early March 2020, looking at the unfolding COVID-19 pandemic in the context of recent history.

 

The full seminar can be listened to here: 

COVID19: Inter-disciplinary approaches (GHH Seminar 144, March 2020) 

Speakers: Dr Owain Williams (University of Leeds), Dr Fang Xiaoping (Nanyang Technological University, Singapore); Dr Kate Mason (Brown University)

This briefing draws upon the material and presentations at that seminar. 

 

 The COVID-19 pandemic silenced the world’s cities in the first half of 2020. Nobody knew what was going to happen, as industries shut down and people were sent ‘home’ (wherever that might be and whatever hardship going home might entail). Reactions around the world to the disease were mixed; some were extremely comprehensive, some were patently inadequate, and many are still to be assessed. Compliance with public health messages was much the same, both within communities and between communities.

 

Yet this is by no means the world’s first outbreak of seemingly uncontainable disease. Dr Owain Williams of the University of Leeds describes the quarantined cruise ships sitting in south-east Asia and off the coast of Japan as “a return to the yellow flag days of previous plague events”. China, where COVID-19 first emerged, has experienced both cholera and severe acute respiratory system (SARS) in the past 60 years. How did the country respond to these three epidemics, and what themes emerge?

 

Cholera

The current cholera pandemic (the seventh in global history) broke out in south-east Asia in 1961 [https://www.who.int/news-room/fact-sheets/detail/cholera]. The following year the disease broke out in Guangdong province and rapidly spread down the south-east coast of China. By 1965 cholera in the area was contained – reduced to a very small number of cases, monitored and treated – as the result of a programme of strict quarantine and isolation.

 

“When a cholera pandemic first broke out in Yangjiang County, Guangdong Province, in June 1961, the central government mobilised medical resources and personnel across the country to impose a cordon sanitaire around the affected areas in order to prevent further spread,” explains Fang Xiaoping, Assistant Professor of History in School of Humanities of the Nanyang Technological University, Singapore. “These interventionist response schemes in Guangdong established a general framework for controlling the cholera pandemic.”

 

Fang focuses particularly on the south-eastern Zhejiang province. A week after the first cholera case was confirmed in Rui’an County in July 1962, the provincial government partitioned the whole of Zhejiang into a series of concentric circles centred on the cholera-affected Wenzhou area. Major observations stations (for identifying confirmed and suspected patients) and temporary joint quarantine stations (into which confirmed and suspected patients were expected to move) formed quarantine ‘rings’ to contain the spread of the disease. The county and city governments divided the area within each ring into further quarantine zones, down to the level of districts and communes. 

 

In addition, the provincial government set up a comprehensive inoculation campaign. On 3 August 1962 directives from the provincial party committee ruled that the entire population in each county of Whenzhou prefecture were to be inoculated against cholera before 15 August – which meant that the local health services had to inoculate nearly three million people within only 12 days.

 

It was not always easy, Fang explains. “The emergency inoculation scheme in the summer of 1962 suffered, due to the poor coordination of local cadres and chaotic information on inoculation subjects.” But from 1963 onwards it was much more of a concerted campaign, with better-organised cadres and reliable inoculation registers. 

 

Two pandemics: building a public health system

Even with the initial stumbling-blocks, this cholera outbreak occurred at a period when China’s health system had started to develop its capacity for handling mass outbreaks of disease. “The medical system (which included the epidemic prevention scheme) did not emerge until the mid-1950s, just six to seven years before the outbreak of the global cholera pandemic in 1962,” Fan explains. As a result, this pandemic presented both considerable challenges, but also the opportunity to restructure and integrate the medical and administrative systems. 

 

For instance, officials in Wenzhou City, Rui’an and Pingyang counties were issued with a detailed timetable for reporting to the provincial health department (although initially, the national reporting scheme lacked adequate staffing and equipment). In 1963, hospitals and clinics set up outpatient departments for intestinal disease, in order to identify and test suspected cases of cholera. The government also committed to establishing complete statistical data on actual and potential cholera patients.

 

And importantly this was also a period when China was very much isolated from the rest of the world’s health community. “When the pandemic broke out in 1961, the People’s Republic of China was not a member of WHO and it remained isolated from the international epidemic reporting network”, Fan explains: although it did keep informed about the global pandemic surveillance network.

 

However, the public health infrastructure in China slowly deteriorated over the following decade, after the death of Chairman Mao in 1976. Finally, in the early years of this century, the Chinese government finally began reconstructing the system and setting up new Centers for Disease Control and Prevention (CDCs). “This was an explicit reference to the US CDC in Atlanta Georgia and was intended to evoke a highly modern scientific ethos,” explains Dr Kate Mason, Assistant Professor of Anthropology at Brown University. It was, she adds, “serendipitous timing” because in 2003 the country was hit by a new epidemic. The CDCs suddenly had a very clear purpose and mandate: containing and preventing SARS. 

 

SARS

Mason was in fact caught up in the SARS outbreak herself. “On 12 April 2003, I was evacuated from my post teaching English at Georgetown University in Guangzhou. I packed my belongings into two suitcases in a duffel bag, got on a bus, crossed the border into Hong Kong and flew with my N95 mask on back to the United States. And at the time I was perplexed by how a virus that up until that point had seemed so thoroughly unimpressive to my friends and colleagues in Guangzhou – which competed with scores of other microbes to cause disease in a tiny minority of Guangzhou’s millions of citizens and that inspired my neighbours to take little more drastic action than to open the windows or repeatedly wash the floors with vinegar – had nevertheless spurred enough panic back home for my sponsor to demand my evacuation back to the United States and my family to attempt to quarantine me.”

 

China’s central government finally admitted the scope of the disease and began instituting control measures, including quarantining entire villages, setting up neighbourhood watch systems to identify potential carriers and building new hospitals in a matter of days. “The WHO praised China's control efforts and credited them in part with the success of the global containment effort.”

 

Controls, freedoms and trust

These measures in China laid the foundations for the way this country responded to COVID-19. They also expose some of the wider issues involved in controlling the pandemic, both in China and elsewhere. “A debate has emerged about whether the nature of the Chinese state has, in a sense, given it a special ability to deal with pandemic events: whether that degree of state control is in some way a positive in this story of attempts to control coronavirus,” Williams says. “We've seen the large-scale deployment of military personnel by the Chinese state, forced testing and forced quarantine of citizens; and China has been roundly criticised by some people in the human rights and health community for its abuse of its citizens’ human rights.” 

 

Mason raises a further issue. There are assumptions of what is permissible and even expected, in China but less permissible elsewhere. “One of the big takeaways that the Chinese government got from SARS is that draconian actions are necessary to control a new virus if it does occur and that China will be praised by the international community if it takes such actions – but only if it does so within its own borders.” 

 

On the other hand, both Mason and Williams point out that many Chinese people themselves do not agree with the idea that these measures are in fact permissible. “Issues of trust and secrecy and cover-ups came to a head, especially with the death of Dr Li Wenliang (the first doctor who recognised and tried to warn about COVID-19, before dying of it himself),” says Williams. In reality, Mason adds, the idea that the Chinese government operates blanket disease surveillance is also far from accurate. “China’s health system operates as a collection of thousands of little fiefdoms at the local level with very little ability on the part of the central government to compel ongoing action in any one of these. What this means in practice is that the central government does not have a lot of power to make local officials report what they are seeing, when they don't want to or feel unable to do so.”

 

Information in the social media age

There is also one glaringly obvious difference with previous epidemics: the way that information has been consumed, perpetuated and manufactured.

 

“In 2003 people whispered of a strange new virus when the news of SARS was officially released and they complained under their breaths about local government responses,” says Mason. “But this happened at a relatively slow pace through word of mouth. In 2020, with hundreds of millions of Chinese citizens cooped up at home with nothing better to do than to look at their social media accounts, there was an explosion of online information, disinformation, and serious discontent the likes of which the Chinese government has not really ever had to deal with before.” 

 

None of this has been restricted to China, as the pandemic spread across the rest of the world: Williams describes it as “a crisis replete with misinformation, with conspiracy theories abounding everywhere”. In a number of different countries distrust of government messages – especially when those messages themselves are conflicting and/or hard to understand – have led to people flatly ignoring advice or rules about masks and/or social distancing (the effects of which have been seen, for instance, in the UK).

 

Health systems and preparedness

The unfolding story of COVID-19 isn’t over yet. Nobody knows what kind of ending it will have, or when that will be reached – or indeed whether it will remain a threat in some parts of the world while others are protected against it. 

 

Williams is particularly wary about the future. “There's a political economy of chronic and continued under-investment in health systems and institutions globally, regionally and locally across the world; and the United States is very much not an exception to that story. We are seeing chronic and continued under-investment in vaccines and prophylaxis. We have neglected health and global health at our peril and I think we will pay the price for that very soon. There's a real story here of politics of fear and neglect and misinformation.”

 

Radhika Holmström is a Wellcome Trust-funded writer and communications specialist working with the WHO Global Health Histories project at the University of York

The many strands of malaria elimination

The WHO Collaborating Centre on Global Health Histories supported by the Wellcome Trust has produced a series of seminars and webinars which look at different aspects of malaria control, and at how this can only be achieved through a combination of approaches.

 

The two seminars can be viewed here:

Can malaria be eradicated? The future of malaria control

(GHH seminar 148, 21 July 2020)

Speakers: Dr Ian Graham, Director of BioYork and Weston Chair of Biochemical Genetics at the University of York), Dr Karen Barnes (Professor of Clinical Pharmacology at the University of Cape Town and Co-Chair of the South African Malaria Elimination Committee), Dr Rajitha Wickremasinghe (Professor of Public Health and former Dean of the Faculty of Medicine at the University of Kelaniya in Sri Lanka)

 

Health Diplomacy: The bases for international and global health

(GHH seminar 164, 6 March 2020)

Speaker(s): Professor Sanjoy Bhattacharya (Professor in the History of Medicine, University of York, UK and Director, WHO Collaborating Centre for Global Health Histories), Dr Lakshmi C. Somatunga Deputy Director General (Medical Services(I)), Ministry of Health, Nutrition and Indigenous Medicine, Sri Lanka)

 

This briefing draws upon the presentations at these seminars, as well as additional conversations with Professor Sanjoy Bhattacharya.

 

“We need to recover the huge amount of information on what makes it possible to implement public health programmes,” says Professor Sanjoy Bhattacharya, director of the Centre for Global Health Histories at the University of York and of the WHO Collaborating Centre for Global Health Histories. “Countries need to recognise the importance of their own implementation histories and experiences and fund the recording of that because they are disempowering themselves by not doing so and falling victim to the idea that the only important ideas were at global rather than the national level. This is a critical history that engages with policy but tries to record all sides of the argument to see which of those ideas made a difference on the ground.”

 

To date, the world has eradicated one human disease [Smallpox]. It is becoming increasingly possible that malaria may follow suit. With a new vaccine showing some signs of success in reducing malaria in young children [https://www.who.int/malaria/media/malaria-vaccine-implementation-qa/en/], and an increasing number of countries being declared malaria-free, along with advances in treatment, the discussions about malaria have moved from control to elimination to the possibility of global eradication.

 

However, the disease is still responsible for hundreds of thousands of deaths every year, almost all of them in Africa and especially among young children. And as Bhattacharya points out, when malaria is finally eradicated, this will be the result of what has (and has not) happened in different countries, specific to those cultures and needs.

 

Effective public health: Sri Lanka

Dr Rajitha Wickremasinghe, who is Professor of Public Health and former Dean of the Faculty of Medicine at the University of Kelaniya in Sri Lanka, describes the reason why the country was certified malaria-free on 6 September 2016 as “nothing but good public health practice”. Along the way, there were definite peaks and troughs: by 1963 the disease had almost vanished from Sri Lanka but then returned (and during this period Sri Lanka also experienced civil war and a huge amount of violence and unrest).  However, in 2009 the country moved from a ‘control’ programme to an ‘elimination’ one, led by the Ministry of Health and two local NGOs and targeting different malaria species in succession. “The interventions were basically universal access to diagnosis and treatment, and vector control” (the use of insecticide-treated nets and/or residual indoor spraying, to get rid of the mosquitoes which transmit the malaria parasite).

 

Much of this good practice, Wickremasinghe explains, involved comprehensive access to control measures (which includes access to education that means people adopt those control measures). “We have an excellent public health system; we have good road connectivity and transport network; we have a literate population, and also there were no counterfeit medicines in the market. Even during the separatist war malaria commodities were provided to rebel-held areas.”

 

 It also involved coordination and a degree of flexibility over how health bodies spend donated funds. And, significantly, the period when a greater proportion of funding was spent on ‘management and other costs’ – in other words, human resources and technical support – rather than insecticides and spraying materials is when the rate of malaria decreased. This is an important counter to the widespread objection to ‘spending on administration rather than frontline costs’ that many potential donors raise.

 

In reality, Wickremasinghe says, “flexible funding which enabled them to do things that government regulations did not otherwise provide was more effective. A programme must be agile and able to respond to the on-the-ground realities.”  An integrated approach is essential, everyone agrees. And that approach has to focus on the people and communities who are at risk of the disease.

 

Experts in their own realities

“Communities are not all the same and of course, because of that, you can't have the same engagement strategy for all communities. There's no ‘one-size-fits-all’,” says Professor Karen Barnes of the University of Cape Town, who is also the Co-Chair of the South African Malaria Elimination Committee. “We've got some good tools that have advanced the control of malaria and aided its elimination in some countries, Sri Lanka included. But each of these tools really depends on community buy-in and community acceptance of what needs to happen. And community engagement must be bidirectional, it's not just a case of the government or the technical experts telling communities what to do; you have to find a way of hearing what the communities think – what they like, what they understand and what they need more of.” 

 

These are the people, she points out, who are “experts in their own realities”. “These are communities that know how bad malaria is. Most people know someone who's died from malaria and they've often had malaria themselves.” (Conversely, areas where malaria rates are low, community buy-in requires a lot more work: communities have, after all, plenty of other concerns that they worry more about than malaria.)

 

Barnes was involved in the Lubombo Spatial Development Initiative (LSDI), a government initiative between Mozambique, South Africa and Eswatini (Swaziland) aimed at enhancing economic development in the area, a key component of which was malaria control. It used a combination of approaches – indoor spraying (the malarial mosquitoes in the area rest predominantly indoors) and/or the use of bed nets to prevent the disease, rapid diagnosis if someone is suspected to have malaria and combination therapies including the drug artemisinin for treatment. All of these require people at risk, or who contract malaria, to take their own action – not least because they need to finish a full course of treatment, rather than stop as soon as they feel better and save the remaining medication for later. “We also needed community engagement to support the very important surveillance necessary to understand how people respond to treatment. Are they cured? Are there factors around a homestead that might put them at more risk of malaria? Have the number of malaria-transmitting mosquitoes been reduced?” 

 

Those experts in their own realities are the people who can bring about real change: for instance,  138 community members in the LSDI volunteered to have window traps on their homes to monitor the number of mosquitoes in their area. However, that only happens if they believe that it’s worth doing and they trust the people doing it; indoor spraying, in particular, involves taking the risk of letting a stranger into the home and in other areas people may refuse this. 

 

In Mozambique, local communities have selected people to be trained as community health workers – either unpaid or with minimal pay. These health workers are trained in carrying out malaria tests, in the correct use of drug treatments, and in recognising when sick people in their community need to make the long journey to the hospital. As a result, many people do not need to leave the local area to travel to a clinic or health centre; the programme is being brought directly to them.   

 

The limitations of treatment

There is also a major concern that the major treatment on offer may become less effective. Dr Ian Graham, Director of BioYork and Weston Chair of Biochemical Genetics at the University of York, has worked on producing hybrid variants of the Artemisia annua plant which can be grown by small-scale farmers. The plant itself has been used as a fever treatment for over 400 years, but it is the specific artemisinin molecule (identified by Chinese pharmaceutical chemist Tu Youyou, who was awarded the Nobel Prize in 2016 as a result) that is usually highly effective, and needs to be produced in larger quantities. It is also most effective as part of combination therapy, and it is very important to keep it as such. 

 

“Artemisinin derived drugs are the most effective treatment for malaria but we already know that the parasite causing the disease can mutate and develop resistance to these drugs, which represents a major public health threat,” Graham explains. “The main way to combat resistance developing is to use artemisinin in combination with partner drugs, as this prevents parasites that manage to mutate and develop resistance to one drug taking hold. Herbal treatments containing artemisinin, using the drug as monotherapy or not completing a full course of combination therapy treatment can all increase the risk of resistance developing. It is essential that we do everything we can to prevent resistance from becoming established, especially in sub-Saharan Africa where local emergence of resistance has recently been reported.”

 

“Artemisinin resistance is a global threat,” says Barnes. “If artemisinins don't work well then, it’s not just that they clear the parasites more slowly. There’s also an increase in the malaria parasites (called gametocytes)that transmit malaria. That means a potential increase in malaria transmission. There’s also more pressure on the other drugs that are being used in the combination treatment, so these partner drugs start to fail too. There are some places in Southeast Asia where there are quite frightening levels of treatment failure: over half the patients treated were not cured by the recommended artemisinin combinations. And we are now getting isolated reports from elsewhere in the world. The impact on malaria cases and deaths if such artemisinin resistance spreads to the Indian subcontinent or sub-Saharan Africa or South America are quite frightening to think about. We'll stop talking about elimination for a long time if that happens.” “It is important to keep looking for alternatives,” Graham agrees. “We are in an arms race with the malaria parasite, which given the opportunity will almost certainly develop resistance.”

 

 

No scope to stand still

Artemisinin resistance is not the only reason why malaria control or elimination programmes have to be, as Barnes says, “dynamic, not static”. In areas where control programmes lose funding and support, the rate of malaria goes up – and that is in areas where communities are very happy to play their part. 

 

In addition, malaria is by definition a very mobile disease. Mosquitoes do not observe regional or national borders. In any case, the borders in many places, like southern Africa, are extremely porous – they are lines drawn up by previous imperial rulers, rather than any division that local people themselves would recognise. This is why regional collaboration like the LSDI, and collaboration between malaria programmes, is essential. 

 

The global plan for elimination is a genuine, and a realistic, goal. However, it will only be achieved if those coordinated, integrated and dynamic programmes are continued – and if they involve the people who are at most risk of malaria themselves.

 

 

 

Radhika Holmström is a writer and communications specialist working with the Global Health Histories project at the University of York.