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Doubts about vaccines

Are strong-arm immunisation campaigns justified in the name of ‘public good’, asks Prabir Chatterjee. What is the ethical responsibility towards those who fall ill despite vaccination -- or because of it? Why is there no notion of parental consent in India? In a shocking instance of unethical practice, the human papilloma virus vaccine for cervical cancer was administered to poor children in boarding schools without their parents’ knowledge and consent

Vaccines are a part of our daily lives today. In India, all children are meant to receive the BCG at birth and be immunised against diphtheria, pertussis, tetanus, measles and polio by the age of 1. The universal immunisation programme is promoted by governments and international agencies. Rules also exist to ensure that travellers are immunised against common vaccine-preventable diseases before they enter certain countries.

India’s immunisation programme costs around Rs 900 crore; our total health budget is Rs 22,300 crore. Clearly, vaccines are widely accepted as playing a critical role in public health. Why then are there disagreements about vaccines -- which ones to use, how they should be promoted, how much the public should know, and their role in public health programmes?

The technology and developments

Antibodies are the body’s response to fighting infection. They are produced by the body when reacting to a virus, bacteria or toxin. Antibodies can be produced by natural exposure to the virus, or by vaccination. Newborn children receive a certain amount of protective antibodies from their mothers, and the first milk, or colostrum, provides the first immunisation. But these early ‘acquired’ antibodies soon wear off. We can prevent some diseases by ‘challenging’ the child with small amounts of the live virus in weakened or ‘attenuated’ form (such as for poliomyelitis), or the dead virus, or a part of it. We prevent others by giving a weak chemical that resembles the toxin (such as tetanus toxoid).

There have been major changes in vaccine technology in recent times, which make them safer, more effective, and easier to administer. For example, ‘multivalent’ vaccines, or combined vaccines for more than one disease, simplify the job of immunising hundreds of thousands of infants for five different diseases. And now, instead of getting the virus to grow on animal cells we use ‘recombinant genetic engineering’. This involves cutting and splicing parts of different cells together. This is believed to be safer than vaccines from ‘cell cultures’ that may be contaminated by viruses from the original animal. New technologies in the preservation of vaccines will replace the mercury compound thiomersal currently used in many vaccines. While small quantities of thiomersal do not cause a problem, there is an additive effect with repeated vaccination (opponents of thiomersal happen to include many non-allopaths). Thiomersal has been phased out in vaccines in developed countries as new technologies are developed and used. But it continues to be used in government programmes in India. Indeed, one possible ethical issue in the development of vaccine technologies is that better technologies may also cost more, and may not be available to everyone. 

Technological developments also introduce new technological challenges. For example, the conjugate pneumococcal vaccine uses an advanced technology, but its large-scale use may create new problems -- a shift from the most common types of infection to less common serotypes -- which will need new solutions.

Vaccine technology is used on healthy people to prevent an illness that may develop. But, like all other drugs, every vaccine can cause problems for a certain number of people, and some vaccines can be a problem for many people. When taking a drug for treatment, the person may weigh the known benefit of the drug against the possible harm. For a vaccine, the person must weigh the possible benefit of the vaccine against the possible harm. For the individual, what is the risk of acquiring the disease compared to the risks associated with the vaccine itself? Then, while the vaccine may harm a few people, it may benefit many more. At the public health level, one therefore has to consider how to balance the risk to a few people with the benefit to many.

How many people should be benefited in order for a vaccine to be acceptable? How many people can be harmed before a vaccine becomes unacceptable? Older, cheaper vaccine technologies may have higher risks, but may be used in public programmes because they are cheaper. What are the ethical implications of such a choice?

Then, there is the concept that if sufficient children are immunised against, say measles, the virus cannot circulate in the community. So individuals who refuse to get vaccinated, because of the risks -- real or perceived -- will benefit from the majority who accept the risk of vaccination.

Finally, many vaccines are given in early childhood and the recipients cannot make an informed decision on whether or not to accept the vaccine. So a proxy -- the parent or guardian -- decides for the child.

Such questions may provide us with a context in which to discuss various controversies about the way in which vaccines are made available and promoted in our society.

Eradication campaigns and their consequences

The first category of vaccine controversies concerns some vaccines that are accepted as useful by the World Health Organisation and the United Nations Children’s Fund and used by governments throughout the world. While there is little controversy within medical circles about the importance of the diphtheria, polio tetanus (DPT) vaccine or the oral polio vaccine (OPV), questions are asked about the highly publicised campaigns to eradicate or ‘eliminate’ (reduce the number of cases to a certain level, as opposed to eradicating the disease from the face of this planet) various diseases using these vaccines on a massive scale. Campaigns such as the polio eradication programme have been questioned because they use a lot of manpower, time and money and may deflect attention from other important tasks. The campaign consists of ‘pulses’ in which all children below the age of 5 are administered the oral polio vaccine with the intention of flooding the environment with a weakened polio virus. The vaccine is thought to replace the wild polio virus circulating, in the hope that the wild virus will eventually be eradicated as it is believed that the virus cannot survive outside the human body for a long period. All government schools and health centres are taken over during the ‘pulse’, disrupting routine health and education programmes. These eradication and elimination programmes raise hopes extremely high but are not necessarily as successful as expected. The pulse polio campaign is more than a decade-and-a-half old (it started in December 1995, in India), but outbreaks of polio continue to occur in parts of the country. At the time of writing, a case has surfaced in Birbhum after a gap of six years, and there are four cases near Farakka in Murshidabad district of West Bengal. Stories are created to boost the image of the campaign, but little transparency is shown when there are setbacks.

Another important ethical concern about the polio eradication campaign stems from the fact that a minuscule number of children getting the oral polio vaccine will get vaccine-associated polio paralysis (VAPP). But, though every child taking OPV faces a small risk of VAPP, a much larger number have been protected from the disease up to now. There is an injectable polio vaccine, which is much safer. But it is more expensive and protects only the immunised child; it will not offer the possible public benefit of the OPV ‘pulse’ that passes through the child’s digestive system and floods the environment with the weakened virus. So the oral polio vaccine is promoted as a public programme.

Should children who develop VAPP receive compensation for the injury they suffered by participating in a public programme? As far back as 2001, the Indian Expert Advisory Group spoke of doing something for all polio victims. However, no such policy has been implemented so far. It is estimated that over 100 children get VAPP in India every year.

In fact, such eradication campaigns build up pressure to get vaccinated. Pressure also builds during epidemics, and the publicity surrounding H1N1 is one example. However, non-epidemics can also be ‘hyped’. Thus, there has been a debate as to whether H1N1 was ever as serious a threat as it was made out to be.

Informed consent and freedom of choice

The belief in ‘public good’ can be very strong. But strong-arm tactics in campaigns usually result in resistance from the public. The best example is in polio campaigns in Uttar Pradesh. Today, there are often six pulse polio rounds a year in Uttar Pradesh, and children may get 21 doses before they are five years old. If a parent objects on the 21st dose, the health department and administration try to penalise the family.

In some countries, parents must give consent for their children to be vaccinated. They are given vaccine information sheets that contain phone numbers to contact if the child falls ill after being vaccinated. Parents may refuse to let their child be vaccinated, though there are rare occasions when the government can appeal to the courts that not immunising a child would endanger a whole community.

There is no notion of parental consent in India. In a shocking instance of unethical practice, the human papilloma virus vaccine was administered to poor children in boarding schools without their parents’ knowledge and consent. At least two of these girls died, though the link to the vaccine is not established.

Inappropriate promotion of useful vaccines

The hepatitis B vaccine is useful in a small section of society that is at risk of infection from the hepatitis B virus (HBV): those in the medical profession, patients who receive multiple injections, those with multiple sexual partners, and children of mothers with hepatitis B. However, companies have allied with social organisations to sell the vaccine at camps. The risk of hepatitis B has been highlighted, even exaggerated. And the vaccine is promoted for people who are not at risk: monogamous, healthy adults who do not work in medical care.

The incidence of HBV infection is not very high: only about 2% of Indians are chronic carriers at risk of further complications and can transmit the infection. In fact a study in the January 2010 issue of the Indian Journal of Community Medicine found that less than 1% of patients at a Jaipur hospital were HBV-positive. Yet, there is pressure to include the vaccine in the universal immunisation programme. At one time, WHO said that large-scale immunisation programmes for hepatitis B made sense only when at least 4% of a country’s population is hepatitis B-positive. Yet, universal hepatitis B vaccination for children has been introduced in some states in India, though the cost doubles the cost of the vaccine programme. Further, researchers Ashok Kale and Anant Phadke have calculated that a lower dose of hepatitis B vaccine, injected just under the skin, is as effective as the full dose that must be given in the muscle. The intra-dermal dose would reduce the cost of immunisation by 80% and be both effective and affordable as a public health programme. However, our government has taken the support of external funding organisations and opted for the larger, much more expensive dose.

Likewise, the haemophilus influenzae B (HiB) vaccine, meant for a particular type of influenza causing meningitis, is used in many western countries and is now being promoted in India though there is no reason to believe that rates of HiB meningitis are as high in India as they are in other countries. (In one Indian study, of 3,400 suspected cases, less than 60 had HiB.) The HiB vaccine is a useful vaccine, but is it a priority in India yet? Still, in April 2009, the government declared that the HiB vaccine would be promoted for the prevention of pneumonia, with the support of the Global Alliance for Vaccines and Immunisation.

Haemophilus influenzae is not the only cause of pneumonia. Another common cause of pneumonia is pneumococcus and there are some 90 types of this bacterium -- but only 23 types of pneumococcus have vaccines. Of these types, some are common in India and others are more common in other countries. At present, there is an effort to introduce a pneumococcal conjugate vaccine (a combination of vaccines against seven sero types of pneumococcus) into the country’s immunisation programme. Community medicine expert Chandrakant Lahariya points out, in the May 2008 issue of Indian Paediatrics, that while childhood pneumonia is a serious problem in India, the actual burden of disease in India is not known. The point here is: should vaccines against a particular influenza, or against a few types of pneumonias, be given priority in our immunisation programme when we don’t know how common these particular illnesses are in our country? Are efforts to introduce these vaccines based on epidemiology or commercial interests?

GAVI

In the July 2010 issue of the Indian Journal of Medical Research, paediatricians Zubair Lone and Jacob Puliyel refer to the “visible and invisible pressures brought to bear on governments to deploy expensive new vaccines”.

The Global Alliance for Vaccines and Immunisation (GAVI) is a consortium of international agencies, set up in 2000, that provides some funds to governments of poorer countries to use newly developed vaccines. Vaccine manufacturers have argued that they must keep the prices of new vaccines high as few countries buy them for the first 20 years or so. GAVI therefore identifies potentially useful vaccines and subsidises their purchase by countries with large populations and low incomes. The argument is that this ensures that the price of the vaccine drops soon, and also motivates companies to research useful vaccines. GAVI was set up with a $750 million donation from the Bill and Melinda Gates Foundation. However, not too long after it was established, criticism emerged that it overemphasised high-tech vaccines, lacked sustainability and transparency, and relied too heavily on private funding.

That criticism is made even 10 years later. GAVI is the principal organisation deciding what vaccines national immunisation programmes will use. It has pressed repeatedly for the expensive rotavirus, pneumococcal and HiB, and hepatitis B vaccines. Such vaccines are irrelevant when DPT has not reached many parts of the world, including India -- just 47% to 65% of the 2.7 crore babies born every year in India get all their shots.

Further, there are still shortages of OPV and DPT. This can be because international donors focus on the pulse polio programme, and there is plenty of evidence of this. In another case, government vaccine units that make DPT at a low price were closed down on the argument that they didn’t meet standards. GAVI then stepped in to fund a private company that would supply the pentavalent (DPT plus HiB plus hepatitis B) vaccine. It then turned out that the private company’s low prices would remain only for a few years. Moreover, the private company was found to have links to friends of political party leaders and acquired vaccine seed cheap from the government laboratories that were closed down.

Unnecessary, low priority, or of questionable value

Though international agencies and our government do not promote or use the herpes zoster (chickenpox) vaccine, the government has allowed its sale. Advertisements in newspapers and on TV for the chickenpox vaccine create unnecessary hype. However, chickenpox does not have the effects of other vaccine-preventable diseases. And the vaccine does not prevent outbreaks, though it reduces the effects (it doesn’t prevent infection, only reduces the severity for the patient).

Recent investigations on an HPV vaccine project in Andhra Pradesh led to the government halting all projects with this vaccine. The report and related discussions on the vaccine have highlighted a number of issues with ethical implications: is the HPV vaccine effective, safe and of public health value? Is it a priority for India? Is it being promoted for public health or other interests?

The HPV vaccine is meant to prevent cervical cancer due to HPV infection, which in turn is usually transmitted by sexual intercourse. A large number of cases of cervical cancer are due to HPV. But even in the West, few countries other than the US and UK have started using the HPV vaccine widely. There are questions about its value. Will it give a false sense of complacency? Will people think that they are no longer at risk of HPV infection or uterine cancer and therefore neglect testing? Will they be careless about having unsafe sex? Will testing for cervical cancer decrease? Screening for cervical cancer is as important as the vaccine, and cannot be replaced by it. Further, 30% of all cervical cancers are not covered by the current HPV vaccines that work only against HPV types 16 and 18. The manufacturer is aware of the limitations of the vaccine but it is promoted aggressively, and this promotional campaign has now started in India.

Programme responses to adverse events

There are proven adverse effects as well as contraindications for all vaccines. The pentavalent vaccine against DPT, hepatitis B and HiB was introduced in Bhutan in July 2009 but was withdrawn from use in September 2009 after six children died following vaccination. A similar problem had arisen earlier in Sri Lanka. Also, there is a fear that the vaccine may increase the risk of asthma.

India has an adverse event reporting system and all reports of illness or death following administration of a drug or vaccine are to be investigated; not all such events are necessarily due to the medicine. The systematic collection of information about possibly-drug-linked events has helped uncover serious side-effects and harm such as the effect of thalidomide on foetuses. Collection of information also helps uncover any weaknesses in the vaccine delivery system. Finally, it helps reassure caregivers and the community when an event is found to be unrelated to the vaccine.

Standard procedures for AEFI reporting were prepared in 2005 and, starting 2006, a large number of cases were investigated for the first time. However, in certain cases it has been left to the media to bring these reports to light. It is sometimes difficult to persuade medical staff that it is to everybody’s advantage to inform state or national authorities about these events. Transparency is not considered important.

The Japanese encephalitis vaccine

One example was in the immunisation campaign against Japanese encephalitis. JE is a mosquito-transmitted viral infection affecting the brain. After it caused a large number of deaths in Uttar Pradesh, in 2005, the Indian government acquired a vaccine from China. The SA-14-14-2 vaccine appears to be safe and effective and may soon be approved by WHO. The number of doses to be given is two, according to the manufacturer. However, experience in Nepal led to the Indian government using a single dose. When the government introduced it in mass campaigns in 2006, there was fear among the public and the press and some doctors opposed the campaign. A number of incidents of illness around the time of vaccination were attributed to the vaccine, and the media highlighted every mistake in the programme. The government’s response was not smart. For instance, when expired JE vaccines were supplied at a campaign centre, one official was quoted as saying that they couldn’t check the batch numbers of all the vaccines. Of course, this is not correct; all health workers know that they have to check the expiry date on the label before giving medicines. This particular official was speaking under pressure from opponents of the vaccine, but such matter-of-fact replies to public doubts and fears are not uncommon.

Place that vaccines have as a technology in public health

Should governments promote the rotavirus vaccine instead of providing clean water? Clean water prevents rotavirus; it also prevents other diseases. Polio, cholera, typhoid are all faeces- or waterborne diseases and can be reduced if our water supplies improve. In the 1970s, a researcher called Thomas McKeown studied mortality due to various diseases in England and Wales over the previous century. Over 90% of reduction in TB, measles and other diseases occurred before vaccines or treatments for these diseases had been discovered.

Further, initiatives like clean water will reduce more than one disease. But the rotavirus vaccine can only prevent some types of rotavirus. It is probably as costly as providing clean water to the community. And there may be risks associated with the vaccine. An older version of the rotavirus vaccine was found to be associated with life-threatening intusussception of the intestines (a potentially fatal situation in which part of the intestine slides into another section, leading to the bowels getting blocked completely) after it was introduced. The newer versions appear to be safer but are very costly.

Conclusion

These are not just armchair debates. In July 2010, the Delhi High Court was expected to hear a case challenging the government’s plans to introduce the pentavalent vaccine into the universal immunisation programme. A pilot project will be conducted in Himachal Pradesh, Kerala, Tamil Nadu, Jammu and Kashmir and Karnataka. The vaccine will cost Rs 350 per dose, against the current Rs 15 for the DPT alone. The petitioners have argued that the vaccine’s safety has not been established -- it has been linked to deaths in Sri Lanka and Bhutan and has been removed from Bhutan’s immunisation programme. Moreover, there is no evidence to justify including the hepatitis B and HiB vaccines in the universal immunisation programme.

It is time for all interested Indians to join the discussion on vaccines.

(Prabir Chatterjee is a medical officer at Bochadanga gram panchayat in North Dinajpur district of West Bengal and a member of Medico Friend Circle. He has also worked in the field of immunisation in Jharkhand and Tamil Nadu)

Infochange News & Features, December 2010