Measles outbreaks in the US are the result of choice. To get vaccinated or not.

But
there’s another vaccine-preventable disease that’s making a global comeback—
whooping cough or pertussis.
Since 2011, whooping cough has become the most common cause of hospitalisation and
death in infants in the UK. Australia, too, saw a particularly severe epidemic between
2008-10. In 2010-11, California experienced its largest whooping cough outbreak in 50
years. Similarly, the incidence of whooping cough has increased in
both Norway and Canadaas well.

All from a disease that is potentially preventable through a routine vaccination.

The signs of resurgence are fast becoming evident in India, too. Although there is no
officially reported nationwide data on incidence of pertussis till date, Indian doctors
have begun to raise red flags. Like Arjun Padmanabhan, a specialist in respiratory
diseases at the Kerala Institute of Medical Sciences in Thiruvananthapuram, Kerala.
Every now and again, one of Padmanabhan’s patients let out a worrying noise while
coughing—the ‘whoop’ sound associated with pertussis.

“Over the last few years, I have started diagnosing cases of whooping cough once or
twice a year,” he says. And each time, he wonders why an ‘ancient disease,’ preventable
with a vaccine used in the government-funded universal immunisation programme
(UIP) since the seventies, is still showing up. After all, India’s UIP has been largely
successful in controlling most vaccine-preventable diseases, such as polio, due to its
reach in the public health system.
What is whooping cough?
Whooping cough or pertussis is a bacterial infection leading to a nasty cough. It can last
for up to three months in adults. In children, it spreads very easily and can even be
deadly. While government programmes using effective and long-lasting vaccines also
offer herd immunity to the entire population, less effective, short-lived vaccines can
compromise this.
When he looked deeper, he found that this resurgence, too, is born of choice. Not about
whether to vaccinate, but rather what vaccine to use. The older, more painful vaccine
used in the UIP or the newer, second generation vaccine sold by pharma majors
GlaxoSmithKline (GSK) and Sanofi Pasteur. Almost counter-intuitively, it is the latter,
introduced in developed countries in the 1990s and later in private markets of
developing countries, that is being linked with the global resurgence of pertussis.
In developed countries, this makes sense. Governments in these countries have
overwhelmingly favoured the second generation vaccine. In India, however, the story is
different. The Indian government has continued to favour the older vaccine for its UIP.
Instead, India’s private market is to blame for the continued popularity of the newer
vaccine and, potentially, the resurgence of pertussis. Despite the government shunning
it, the newer vaccine is more popular in India’s Rs 1,992 crore private or self-pay
vaccine market. The question is, why?
What’s up, doc?

Despite being vastly smaller than the public vaccine market in terms of volumes, the
private market is far more lucrative. For example, the government’s UIP, which caters to
the vast majority of citizens—well over 85% by industry insider estimates—had a total
budget of Rs 3,500 crore in 2017-18. The private market, despite accounting for
comparatively meagre volumes, was still worth a shade under Rs 2,000 crore. And the
king-maker in the private market is the 25,000-strong Indian Academy of Pediatrics
(IAP). The private market is founded on its recommendations.

So, if you’re a vaccine manufacturer, you can either go through the painful process of
evangelising individual paediatricians to prescribe and sell your vaccines or convince
the association itself to make a recommendation. And even though the Medical Council
of India (MCI) bars individual doctors from receiving gifts or perks from drug or vaccine
manufacturers so that commercial interests don’t influence prescriptions,
paediatricians have favoured the newer vaccine. And it’s easy to see why.

GSK and Sanofi’s pertussis vaccine is marketed as ‘pain-free’. The older vaccine, though,
which many of us will remember from the Diphtheria Pertussis Tetanus (DPT) vaccine
which leaves a tiny scar on the arm, is anything but. The older pertussis vaccine also
causes babies to cry for hours and often leads to cases of fever and rashes as well.
Adding to the allure of the newer vaccine is the fact that it offers higher margins—up to
100%—than vaccines which contain its older counterpart.
Unsurprisingly, doctors were an easy sell. This, despite the proven track record of DPT,
which is responsible for bringing down cases of whooping cough in India from over
320,000 in 1980 to about 24,000 in 2017.

The IAP, though, proved a tougher nut to crack. One of IAP’s office bearers at the time—
Dr Vipin M Vashishtha—studied the pertussis resurgence in developed countries and
found that the effectiveness of the GSK/Sanofi vaccine waned faster than that of the
older vaccine. He recommended that Indian paediatricians prescribe the older vaccine
instead of the newer one—effectively seeking to establish the same standard for both
the private and public market. Following on from this, the IAP issued guidelines
advocating against the newer vaccine.
Two kinds of vaccines
Whole-cell pertussis (wp) vaccines are first generation vaccines and were originally
available in combination with diphtheria and tetanus vaccines. Immunisation with wp
vaccines was considered effective, but is frequently associated with minor adverse
reactions such as redness and swelling at the site of injection, along with fever and
agitation. To address the adverse reactions observed with wp vaccines, the acellular
pertussis (ap) vaccine—a second generation vaccine—was developed in Japan in 1981.
“For a vaccine to be successful in the Indian retail market, it needs two approvals. One
from the Drug Controller General of India (DCGI), and a second from the IAP,” says a
former marketing executive with Sanofi, who promoted vaccines for the MNC until
2009. IAP’s guidelines are followed very seriously by most paediatricians, which is why
a company can not launch a vaccine in the retail market without their recommendation,
he said.
However, in a curious about-turn, the IAP made it official in 2018 that its paediatricians
could choose between either of the vaccines. Vashishtha, who was the convener of IAP’s
committee on immunisation from 2011 till 2016 and had recommended the older
vaccine, has been kicked out of the IAP’s immunisation committee. All of this with a little
help from an MCI loophole.
The art of giving
Today, Vashishtha is a director with Mangla Hospital and Research Center, Bijnor, in
Uttar Pradesh. He minces no words when talking about his experiences advocating
against the newer vaccine. His recommendation, he says, was met with resistance from
IAP’s members, including office bearers and key opinion leaders.
“People were not willing to make such a huge change even after we studied the data that
resurgence of pertussis in Western countries was associated with the vaccine
(manufactured by Sanofi and GSK),” he said. “WHO data clearly shows that the whole-
cell vaccine (older vaccine) has been efficacious in bringing down the incidence in India,
but the newer vaccine that has no data to prove efficacy in India was being used in the
private market.” It just relied on the word of the vaccine manufacturer and followed the
lead of developed countries that had adopted this vaccine.
The reason for all this, Vashishtha alleges, is that multinational vaccine manufacturers
offer the IAP a host of perks. Yes, despite the MCI barring vaccine and drug
manufacturers from offering gifts and perks to doctors, manufacturers still have a way
to influence choices, both at an organisational as well as an individual level. Through
sponsorships for events like annual conferences or individual research grants,
respectively. This loophole that has led to the entire vaccine marketing strategy being
focused on the IAP as well as targeting individual paediatricians to indirectly promote
their products, Vashishtha alleges.
Pedicon 2018 sponsorship rate list
Rs 5 crore for one titanium sponsor,
Rs 4 crore each for two platinum sponsors,
Rs 3 crore each for three gold sponsors,
Rs 2 crore each for four silver sponsors
According to an IAP member, who asked not to be named, Sanofi along with other
vaccine manufacturers sponsor more than 50% of the costs of Pedicon, the annual IAP
conference. Sanofi did not respond to a detailed set of questions sent by The Ken. IAP’s
president-elect Digant Shastri also refused to talk to The Ken and IAP did not respond to
emailed questions sent by The Ken.
GSK, however, stated that it “participates in various scientific congresses organised by
medical associations (e.g. IAP, FOGSI) where latest scientific updates are shared.” GSK
India’s spokesperson also stated that, although it does not pay doctors to speak at
events, GSK does fund research by doctors on its vaccines and engages with doctors in
an advisory capacity on a need-basis.
Spare the rod and spoil the child
Seems like an open-and-shut case, right? Not quite. To imagine that the IAP is wholly
influenced only by financial incentive is both cynical as well as simplistic. At the end of
the day, it also comes down to the motivation of consumers in the self-pay market, and
this is something that the multinationals have been able to play to.
By 2010, Sanofi’s five-in-one pentavalent vaccine—which included inactivated
poliovirus (IPV), HiB, diphtheria, tetanus and pertussis—dominated the Indian private
market. It played right to the concerns of the private market. As Vashishtha explains, the
priorities of the government and private customers are very different. The government
cares about cost, efficacy, and safety (adverse events like fever, rash, etc.) in that order.
This is why it continues to use the older, cheaper pertussis vaccine. Paying parents,
however, care most about the adverse events, then about the efficacy, with price being
an afterthought.
Sanofi’s promotional campaign understood this well. The marketing campaign for
Pentaxim—its pentavalent vaccine launched in 2007—centred around the vaccine’s
ability to not only protect the child from five diseases but also ensure that babies would
cry less and get no fever or rash as a result of the vaccine, says one of the former
marketing executives with Pune-based Serum Institute of India. Serum is the world’s
largest vaccine manufacturer.
Serum launched its own pentavalent vaccine in 2010, which included the older
pertussis vaccine. With Sanofi dominating the market, Serum went all out to dismiss the
importance of Sanofi’s USP of painlessness. It even put out brochures like this one:
It was a necessary promotional campaign as Serum’s medical representatives (MR) had
to convince paediatricians to choose the efficacy of Serum’s vaccine over its more pain-
free counterpart, said the former Serum marketing executive, who was part of Serum’s
2010 efforts. But this proved to be an uphill task. Paediatricians were concerned about
the low rate of adverse events caused by the second generation vaccine and parents
wanted the pain-free option. “It was a no brainer which vaccine would sell when a
paediatrician calls one painful and another pain-free,” says the vaccine business head of
a south India-based vaccine major that is one of the few that produces a
pentavalent vaccine.
As such, the market continued to be dominated by Sanofi even after Serum launched its
pentavalent offering with the older pertussis vaccine. Until 2013, that is, when IAP took
a cue from global outbreaks of pertussis and recommended the first generation vaccine
over the newer one.
Doctor’s orders
The 2013 guideline from IAP wasn’t taken lying down though. In fact, as the former
Serum marketing executive recounts, it was the start of strong pushback from
individual paediatricians. “Paediatricians obviously wanted to use the Sanofi vaccine as
its price was 3X of ours with margins of up to 100% and was preferred by parents,” he
says.
Vaccine margins are the bread and butter of paediatricians with private practices. At the
time, the former marketing executive says, the pentavalent vaccine sold by Sanofi was
priced at Rs 4000 (The Ken could not independently verify this. Today, it’s priced at Rs
2,495.) It also offered margins of over 80%. Serum’s pentavalent offering, meanwhile,
was priced far lower—about Rs 400—and provided maximum margins of 50%.
Understandably, individual paediatricians felt they were being short-changed.
Adding weight to their stance was the fact that Sanofi’s pentavalent vaccine also
contained IPV, which inoculates children against polio. The Indian pentavalent vaccines,
however, substituted IPV with a vaccine for Hepatitis B, as Sanofi held a monopoly over
IPV.

Coincidentally, 2013 was also when India began facing an IPV shortage. As such, Indian
parents were insistent on the vaccine that protected against polio. IPV is the reason that
Sanofi’s pentavalent vaccine became a Rs 150 crore-plus single brand in India in just
three years, says the vaccine business head quoted above. On its own, Sanofi’s
pentavalent vaccine brought it more money than the government’s entire bid for 14.5
million doses of the rotavirus vaccine, which amounted to just Rs 104.13 crore.
As a result, while IAP’s recommendations did lead to a marginal rise in the sales of
Indian pentavalent vaccines, the IPV shortage meant Sanofi’s pentavalent vaccine
remained indispensable. And eventually last year, the IAP itself caved and withdrew its
earlier guidelines against the newer vaccine.
Point of no return
Since the IPV shortage began in 2013, the retail market has been dominated by GSK and
Sanofi’s hexavalent vaccines—a hepatitis B vaccine has been added to the pentavalent
offerings. Indian vaccine manufacturers, on the other hand, remain stuck with their IPV-
less pentavalent vaccines and have focused on the public market or UIP. Barring IPV and
Pneumococcal Conjugate, which the UIP procures from Sanofi and Pfizer, respectively,
all other vaccines used in the UIP are either supplied by public companies or private
Indian ones.

Can Indian vaccines with the older pertussis vaccine mount a comeback in the private
market? Only if they can produce hexavalent vaccines with IPV, believes the former
vaccine business head quoted above.
But if the newer vaccine is leading to a resurgence of pertussis, is there a way back for
the older vaccine in today’s private market? Ashish Bavdekar indicates there isn’t.
Bavdekar, a consultant paediatrician at 550-bed multi-specialty KEM hospital in Pune, is
looking for the incidence of pertussis among infants under one year of age. He is trying
to determine whether the second generation pertussis vaccine can be marketed to
pregnant Indian women, so as to protect the infant as well. Bavdekar has received a
grant from Sanofi for the same.
“Vaccines for pregnant women are coming in a big way in the West. In the UK and
US, the pertussis vaccine is recommended to pregnant women. We will know if
India needs them if we collect data on incidence of pertussis among infants”
ASHISH BAVDEKAR, PAEDIATRICIAN
Bavdekar believes the only way for the Indian private vaccine market is forward. He
points to developed countries sticking with the newer vaccine rather than reverting to
the older one. Instead, these countries have introduced additional—booster—shots of
the newer vaccine to extend the duration of protection from pertussis. In time, he
expects the IAP will make a similar suggestion. More data will only help. Bavdekar
would not reveal how many cases of pertussis he has found in the four months since the
study started. However, he does mention that he has found cases across four hospitals
in four regions across the country. He remains mum on whether these babies had
received the newer pertussis vaccine, the older one, or neither.
In the same vein as Bavdekar’s suggestion, both GSK and Sanofi are in favour of
additional doses of the vaccine. GSK India’s spokesperson accepts that the immunity to
pertussis provided by their vaccine wanes over time, and says that booster vaccination
is needed to maintain protection. The spokesperson, though, rubbished any suggestion
that the efficacy of GSK’s vaccination was to blame.
The World Health Organisation (WHO), for its part, acknowledged both vaccines as
having “excellent safety records” in 2015. The WHO suggestedthat countries could use
either. However, it said that national programmes currently administering older
vaccines should continue to use it, while nations using the second generation vaccine
should also continue using it, but should consider the need for additional booster doses
as well as additional strategies such as maternal immunisation in case of a resurgence of
pertussis. A diplomatic solution for a war with no clear bad guy.