Pentavalent: The Killer is Back

The vaccine reversal
9 July, 2010 - So far, health officials remained defensive about relating the contentious pentavalent vaccine with the deaths of eight infants shortly after receiving the shots.

This week their defense seemed rather to be flagging. Which was only to be expected; as the people began to realise that no such cases surfaced, in almost a year after the vaccine was suspended.
All this while, health officials had been parroting what the world health organisation claimed of the deaths being coincidental, not one or two, but all eight infant deaths.

During the yearlong suspension of the vaccine, cases of the five infants were sent abroad for expert examination and investigation; which, without an autopsy, ruled out any connection between the vaccine with the children’s deaths.

World health organisation officials attributed the death to their history of suffering from epilepsy, viral infection and inflamed brains.

It is still a mystery if these children really had a history of such infections, which only health experts can tell. Would they have the audacity to tell the parents if it were untrue?

All they have reiterated so far is they diagnosed meningo-encephalitis, an inflammation of the membrane protecting two of the most crucial parts of a human body, brain and spine, as the cause of the death.

How derisible that children, who were all up, healthy and playful one moment, were suddenly bedridden, following shots of the vaccine; and the flaw was not with the vaccine, but the children.

Health officials and world health organisation experts went to the extent of saying an estimated 541 children would have died anyway, from some common diseases and infections, going by the country’s infant mortality rate, calculated at 40.1 for every 1,000 live births.

But the children, who died following the vaccination, wouldn’t necessarily have made that number.

It has become a robotic response for Bhutanese to blurt out that, as a developing nation, we have the advantage of learning from the flaws of other countries.

Pentavalent vaccine was introduced in Sri Lanka in January 2008, but three months later it was withdrawn, because of 25 serious adverse reactions, including five deaths.

Similar cases were reported in South Africa and our immediate neighbour India. What did we learn? We basically fell into the same ditch, others before us did.

But it is a lesson nevertheless. We will be more careful and ask some tough questions before introducing any new vaccines or drugs in future.

After all, it was not under the pressure of avoiding some disease with potential of becoming a pandemic that the pentavalent vaccine was introduced.

The remaining drugs, bought at a significant cost, meanwhile appear to be a profligate exercise in futility


Reintroduction deferred
Technical committee postpones re-launch by a year
Pentavalent Vaccine 8 July, 2010 - The health ministry’s technical committee on vaccines has decided to further postpone the reintroduction of pentavalent vaccine for a year.

“We took this decision, since no new cases of meningo-encephalitis was reported after its suspension, which couldn’t be explained either by the WHO reports or with scientific reasons,” said the public health director, Dr Ugen Dophu. “The technical committee acknowledged the WHO’s reports, but they still decided to postpone the reintroduction of the pentavalent vaccine by a year, because of this temporal relation,” said the public health director.

No case since vaccine stopped
Meningo-Encephalitis No case of meningo-encephalitis has been reported so far among children below one year, ever since the pentavalent vaccine was suspended eight months ago, said health officials. Last year, doctors at the Thimphu referral hospital and “experts” from WHO diagnosed meningo-encephalitis as the cause of death in the eight babies that died shortly after receiving the pentavalent vaccine.
However, this “temporal relation” between the vaccine and meningo-encephalitis cannot be explained either by the world health organisation’s “investigation” reports, nor with scientific reasons, said the public health director, Dr Ugen Dophu.

“Qualitatively there is not a single case of meningo-encephalitis reported after the vaccine was stopped,” Dr Ugen Dophu said.

Meningo-encephalitis is an infection that causes inflammation of the brain and the membranes surrounding the brain. WHO also recommended the health ministry to do a study on the disease burden in the country.

But the disease so far has not received much attention.

The department of public health (DoPH) told Kuensel the ministry’s research unit is doing a study on the disease burden in the country, so that decisions, such as starting a program and appointing officials could be taken.

However, the officiating head of the research unit said that they are not aware about any such study. The Thimphu referral hospital has also not received any official directives from the ministry, said the hospital’s medical superintendent.

“We’ll strengthen our adverse effects following immunisation (AEFI) system on all vaccines, by improving the reporting system, surveillance system and capability of all health workers,” said Dr Ugen Dophu.

In the past five years, records with the Thimphu referral hospital showed that Bhutan saw a total of 122 cases of meningo-encephalitis, with 24 deaths in all age groups.



The one-year suspension started in May after the committee’s last meeting.

This means the health ministry will not use the 26,000 left over doses of pentavalent vaccine that expires on January 2011. “That’s worth about USD 84,000 and we can’t return it to the manufacturers. And, if we include the disposable charges, it would come to about USD 100,000,” said Dr Ugen Dophu.

Also, the new vaccines that would be reintroduced will not be bought from the same manufacturing company based in India. For this decision also, the committee has given no scientific reasons, said Dr Ugen Dophu. “Bhutan will instead use vaccines, manufactured by a Danish company, that Nepal and Sri Lanka are today using,” he said. “These vaccines, I believe, are more expensive.”

The committee’s decision was accepted during the progress report and coordination meeting (PRCM), the health ministry’s highest decision-making body.

Meanwhile, the only document with the health ministry that recommends the introduction of pentavalent vaccine into the country’s immunisation program, is a WHO-funded rapid assessment on Haemophilus influenza (Hib), done in 2002 on children less than five years.

A copy of the assessment with the vaccine preventable disease program in the DoPH is however “lost”, said a health official. The assessment was done in three referral hospitals, said an official from the vaccine preventable disease program.

Some information from the assessment is there in the pentavalent vaccination manual for health workers. It stated, “It found that Hib meningitis cases were estimated at 80-270 cases a year, which is comparatively high for Bhutan.”

The assessment further said, “Since Hib is the predominant cause of bacterial meningitis, and Hib pneumonia is estimated to be five times more common than Hib meningitis, introduction of Hib vaccine will have a significant impact on reducing morbidity and mortality in children.”

While this may have been “enough evidence” to warrant the vaccine’s introduction, Kuensel learnt that the global alliance for vaccine initiative (GAVI) had some budget but was running out of time to spend it.

It was then decided to use the money to buy the vaccines for Bhutan, without much research on the vaccines. It also learnt that the WHO investigating “experts” did not know how to go about their investigation into the deaths.

Meanwhile, the public health director said that those with grievances regarding the vaccine could appeal anywhere they want to.

By Sonam Pelden


Technical committee to decide re-introduction



5 July, 2010 - The health ministry’s “technical committee” is meeting this week to decide on “re-introducing,” the controversial pentavalent vaccine into Bhutan’s immunisation programme.

The director of public health, Dr Ugen Dophu, said that the 11-member committee, would research, discuss, decide and then advise the immunisation program with the department of public health (DoPH), on the vaccine’s reintroduction. The health ministry suspended the use of pentavalent vaccine on October 23 last year after four deaths were reported. In all, eight deaths were reported.
“Their advice is most valuable,” Dr Ugen Dophu said of the committee that comprises “experts” in pharmacy, the drug regulatory authority, paediatrics, medical specialist and the research unit.

The world health organisation (WHO)’s investigation report in May had said the deaths of infants were not due to the vaccine. “The WHO is the technical advisor for most countries and the health ministry is convinced the deaths were not due to the vaccine,” the public health director said. “But we still need our technical committee’s decision before we start. They have good medical knowledge and we can rely on their decision.”

If the technical committee decides the vaccine’s re-introduction, he said that it would take about two months time to start it again. “All vaccines were recalled to Thimphu, so it has to be distributed again,” he said.

Unlike before, where it was said that parents would be given a choice between the tetravalent vaccine and the pentavalent vaccine, Dr Ugen Dophu said that only one of them would be in the immunisation schedule. “If the pentavalent vaccine is re-introduced, the tetravalent vaccine will be withdrawn,” he said.

This was because the health ministry, he said, cannot afford to buy both the vaccines. “Each dose costs USD 3.23 and Bhutan is paying only 0.23, while the rest of the cost is borne by GAVI,” he said. “The tetravalent vaccine we have in stock will last for only about three months,” Dr Ugen Dophu added.

However, parents would have the choice to “not” immunise their babies. “We have learnt a lesson and we won’t make it compulsory,” the public health director said.

Even after the reintroduction of the vaccine, the health ministry does expect cases of side effects like fever and swelling. “But not deaths due to the vaccine,” Dr Ugen Dophu said. “In Bhutan, there are 140 deaths in every 10,000 births and there may still be deaths from other causes even after the vaccine is reintroduced.”

To implicate that the vaccine is responsible for the deaths after it is reintroduced, an investigation has to be done again. “But it won’t be like last time, where we suspend the vaccine and all,” Dr Ugen Dophu quickly added.

This time, with the improved survellieance of meningo-encephalitis, the disease that was diagnosed as the cause of deaths in the eight infants, and health workers across the country well informed on identifying the signs of the disease, Dr Ugen Dophu said that any such case would be reported and samples tested immediately.

“Meningo-encephalitis is a national concern now,” he said. “It was always there, but before the focus was more on meningitis, which is easier to diagnose and on others like dysentery and diarrhoea.”

By Sonam Pelden


Immunisation yet to resume
Despite WHO’s go ahead, officials uncertain
Pentavalent Vaccine 5 June, 2010 - The fear injected into the minds of parents to expose their newborns to the pentavalent vaccine has left health officials unclear about whether to resume the immunisation.

Two representatives from the world health organisation (WHO) in their investigation report, however, said the vaccine should be resumed, since no evidence was found to suggest a link between use of the vaccine and the occurrence of meningoencephalitis, an inflammation of the membranes of the brain and the adjoining cerebral tissue.

Experts and health officials attribute the cause of infant deaths to meningoencephalitis, while some succumbed to epilepsy and other infections.

In fact, soon after cases of babies dying, days after the vaccination, the WHO team in November last year, looked into records maintained in the Thimphu national referral hospital of children and adults of all ages suffering from meningoencephalitis.

The first infant death was reported on September 12 following pentavalent vaccination, introduced on September 1 last year. Four more infants, vaccinated with the pentavalent were admitted to the hospital between September 10 and October 23. Health ministry suspended the vaccine on October 23 after four of the five infants died. Subsequently, three infants deaths were reported from Samtse and one from Paro.
Diphtheria, pertussis and tetanus (DPT), hepatitis B and haemophilus influenzae type b (Hib) together make up the pentavalent vaccine.


They found an increase in the reported number of children and adults with meningoencephalitis from seven and six between 2006 and 2007 to 19 and 16 between 2008 and 2009.

Although a slight drop in the case between 2008 and 2009, children in their sixth month suffering from meningoencephalitis increased to 10 in 2009 from six in 2008.

A nationwide record of the case under national health management information system, which regularly reports data on meningoencephalitis showed an increase in the cases from 165 and 152 between 2006 and 2007 to 256 and 352 between 2008 and first half of 2009 (January-June).

However, the cases among children below five years dropped to 63 and 89 between 2008 and first half of 2009 from 90 and 108 between 2006 and 2007.

“WHO team told us to strengthen the care of meningoencephalitis than worry about the vaccine,” Dr Ugen Dophu said.

He said that, besides sending two sets of four cerebral computed tomography of the nine infants, who died days after receiving the pentavalent vaccine, for experts in Australia and Canada to examine, some 40 random vials of the vaccine were sent for laboratory testing in Paris and Bangkok.

The two specialisd laboratories passed the vaccines as fit for use, which inadequate to prove much, Dr Ugen Dophu said they were experimented on live animals like frogs, rats, guinea pigs and monkeys.

“They were observed for two months and showed no signs of illnesses,” he said. “In fact, they grew stronger after receiving shots of the vaccine.”

Dr Ugen Dophu explained that vaccine production had to undergo four phases of research into appropriate viruses to use, safety, experiment on live animals before finally trying it on humans.

“All countries should be willing to try,” he said. “Not that a few countries try, so others can watch and decide whether to join.”

Countries trying a particular vaccine were normally provided with it from the factories at a highly subsidised rate throughout.

For the pentavalent vaccine, the health ministry paid USD 3.27 a dose for which USD .23 was paid from the health trust fund, and global alliance for vaccine initiative (GAVI) chipped in the rest. Launched in 2000, GAVI is a global health partnership representing stakeholders in immunisation from both private and public sectors.

Incomplete clinical data and lack of autopsy reports and specimen, the report pointed out, from the affected children was a limitation for proper evaluation to understand the causes of death.

Autopsy, Dr Ugen Dophu said, was inappropriate from the country’s cultural point of view.

On the vaccines side affects, Dr Ugen Dophu said one in 100,000 would react abnormally. “Side affects like swelling, fever and illness for a couple of days are globally accepted in the scientific world,” he said. “It’s toxicity that’s not tolerated.”

The report said that of 634,982 population size, annual birth was about 13,500. With the country’s infant mortality rate calculated at 40.1 for every 1,000 live births, the report stated that the estimated number of infant death was around 541.

“Approximately 73 infant deaths would be anticipated between September 1 and October 23, 2009 (time between introduction of the vaccine and reports of death of infants),” the report said, adding that reported number of infant deaths for 2008 and 2009 were unavailable.

Dr Ugen Dophu said the health ministry was under pressure to reduce the infant mortality rate, which, without resumption of the pentavalent vaccine, was difficult.

“Should we completely stop the use of vaccine, which may save 1,000 lives, because of five deaths not necessarily caused by it?” Dr Ugen Dophu asked.

By Samten Wangchuk



Likely to resume

Decision on the vaccination program after immunization committee consensus
Pentavalent Vaccine 29 May, 2010 - After six months of investigation into the suspected death of four infants, the pentavalent vaccine was ruled out as the cause of death and the vaccination programme will most likely resume, according to the health secretary, Dasho (Dr) Gado Tshering.

The secretary said that the decision to resume would, however, be made only after the immunisation committee, which included stakeholders from the public, discuss and decide.

“People still perceive it as dangerous so, if it is reintroduced, it will be done very judiciously,” he said.

If the vaccine were to be reintroduced, parents would be given the choice to either have their infants given the pentavalent or the tetravalent shots.

The health secretary, along with the national committee for immunisation practices, were presented with the investigation report by two representatives from the world health organisation (WHO). The report was however not fully disclosed to the media.

The findings supported that the deaths were coincidental and not linked to the vaccine, according to the representatives, Dr Patrick Zuber from department of immunisation, vaccine and biologicals, and Jayanta Liyanage, WHO regional officer in south-east Asia.

Jayanta Liyanang said that, in October, the two preliminary investigations were done, after collecting all possible information and talking to parents. The infant death sheets and reports were then sent to Dr Lloyd Morris in Australia and professor Noni McDonald in Canada for review.

The experts said that the final findings were that the vaccine was not at all related to the deaths. “It was coincidental.” When brought to the hospital, the five infants, who include one survivor, were clinically diagnosed with diseased central nervous system, said Dr Zuber. “But the investigations revealed that the causes were different.”

Dr Zuber explained that two of the infants had inflamed brains, one had a history of epilepsy, one had a history of general systemic infection and one had viral infection.

To further support their report, a data of similar deaths of infants below one year of age were also collected from 17 hospitals in the country. “There were 19 similar cases, of which seven died a sudden death,” said Jayanta Liyanage. This, according to the experts, reconfirmed that the suspected deaths were purely coincidental.

In Bhutan, the infant mortality rate is 40 deaths for every 1,000 births before becoming a year old. “Basically it means if 13,000 babies are born in a year, roughly 550 die before their first birthday,” said Jayanta Liyanage. “Even after reintroduction, such cases will happen.”

“I’d say it’s almost 100 percent safe to relaunch the vaccine,” said Dr Zuber.

Dr Zuber said, initially, even the two African countries, who had received the vaccines from the same batch sent to Bhutan, stopped the vaccination program. The programme has been relaunched,” he said.

The representatives said that, since 2001, millions of vaccines have been used with a good record of safety. “Fever and convulsions have been involved, but there were no casualties associated,” said Dr Zuber. “The specifications are the same and the vaccines had followed stringent WHO standards.”

There were two types of pentavalent vaccines. In Bhutan and other developing and LDCs the whole-cell pertussis vaccine was administered; and in the industrialised countries, the acellular pertussis vaccine was administered.

By Kinley Wangmo





Report or recall: DRA
Pentavalent Vaccine Update15 April, 2010 - The drug regulatory authority (DRA) has written to the department of public health (DoPH) and the world health organisation (WHO) in New Delhi, India, to send the experts’ reports on the suspended pentavalent vaccine by the end of this month, or else the vaccine would be withdrawn from Bhutan’s vaccination programme.

Only nine days are left for the health ministry’s six-month suspension of the pentavalent vaccine, which allegedly caused the death of eight infants last year, to be over.
DRA officials said that, after the suspension order, it sent about 300 samples of the vaccine for testing. “We need to have certain regulatory measures based on their reports, so that we can notify the health ministry accordingly,” head of DRA and drug controller, Sonam Dorji said.

He said that if the reports don’t reach them by the end of this month, they would recall the product and deal with the vaccine suppliers accordingly. Sonam Dorji said that the issue would be discussed during the board meeting on April 22.

“Biological tests do take time, unlike chemical tests, but we’ve given them enough time and this is a reminder,” he said. “We don’t know if it’s the compilation of the report that’s taking time or if it’s the report itself.”

The public health director, Dr Ugen Dophu, said that DRA has “threatened” the public health department with their letter. “What they’re doing is right and they have the authority to withdraw the vaccine,” he said.

He, however, said that the reports could reach Bhutan only by the first week of May. The five in one combination vaccine against diphtheria, pertussis, tetanus, haemophilus influenza B, and hepatitis B was suspended on October 23 last year after the deaths of eight babies, who had received the vaccine.

In a press conference earlier this month, the prime minister told the media that the government is very concerned about the issues surrounding the pentavalent vaccine.

By Sonam Pelden


No news but bad news



Pentavalent Update 23 March, 2010 - With only a month remaining for the investigations into the pentavalent vaccine to be over, parents, who lost their newborns, allegedly to the vaccine after they were inoculated with it, are restless to learn of developments.

But health officials are still waiting for updates on the tests from the world health organisation (WHO).
The combination vaccine against diphtheria, pertussis, tetanus, haemophilus influenza B, and hepatitis B was suspended on October 23 last year after the deaths of eight babies, who had received the vaccine.

Health officials said they were expecting a team from WHO, south east Asia regional office (SEARO) in Delhi only on May 26 with the reports. “The regional team will then have further discussions with the health ministry regarding the vaccine and the reports,” the WHO representative to Bhutan, Dr HSB Tennakoon said. “They were supposed to come in April but it was postponed because of the SAARC summit.”

However, Kuensel learnt that the report of the cerebrospinal fluid (CSF) has reached the WHO office in Delhi, which said the vaccine was not the cause of the deaths.

The CSF sample of one of the babies was sent to the centre for disease control and prevention (CDC), in Atlanta, USA in early December 2009. But the ministry is yet to hear from the two laboratories in France and Thailand, where vaccine samples were sent for quality testing on January 31.

Even as Bhutan awaits its reports from international experts and laboratories, the pentavalent vaccine remains a controversial issue.

Last month, a group of medical experts in India, led by a former health secretary, filed a public interest petition to the Delhi high court against the government’s plans to introduce pentavalent vaccine into the national immunisation programme without proper epidemiological studies.

The petitioners complained that, evidence from several countries did not favour the introduction of pentavalent vaccines in the country.

The petition said that the pentavalent vaccine was introduced in Bhutan, but withdrawn after eight deaths in October 2009. Before that, the, petition stated, it was withdrawn from Sri Lanka after 25 serious adverse reactions and five deaths.

“Given the grave risks from this new vaccine, it is humbly prayed that introduction of pentavalent be stayed till a thorough evaluation is complete,” the petition read. “That includes evaluation of data of strain replacement from Canada, diabetes in Finland and deaths in Bhutan.”

On February 19, this year, WHO recommended a temporary suspension of the distribution and use of pentavalent vaccine, Shan5. This action was taken as a precautionary measure, pending investigation of vaccine quality complaints from Colombia, Comoros and Nepal.

A month later, on March 12, WHO recommended all countries that had the Shan5 vaccine to stop procurement and its use. Distribution information indicated that the Shan5 vaccine had been supplied through UN agencies or by direct procurement to Central African Republic, Chad, Colombia, Comoros, Democratic Republic of the Congo, Lao People’s Democratic Republic, Mauritania, Mozambique, Nepal, Nicaragua, Pakistan, Republic of Congo and Tanzania.

By Sonam Pelden


Investigations over, reports awaited



25 January, 2009 - The World Health Organisation (WHO) has finally identified two laboratories in France and Thailand to quality test the samples of the pentavalent vaccine that the health ministry suspended four months ago after nine babies that received the vaccine died.

The testing of samples say public health officials is one of the most important and the final step in the investigation process, that would help confirm whether the vaccine had any role in the deaths of the nine infants.
The labs identified are the division of biological products, department of medical sciences in Bangkok and the Agence Française de Sécurité Sanitaire de Produits de Santé (AFSSAPS), Direction des Laboratoires et des Contrôles, Unité de Contrôle des Médicaments Immunologiques in France.

Public health director, Dr Ugen Dophu, said the testing of samples is an important part of the investigation. “The review of the patient’s history and the testing of the cerebrospinal fluid are equally important, but this would test the quality of the vaccines,” he said.

With the laboratories identified for testing, the investigation part, said Dr Ugen Dophu, is over. “Now we have to wait for the reports from the experts and the laboratories to confirm if the vaccine was or wasn’t responsible,” he said.

The investigation process began on October 29 with the arrival of an expert team from the WHO. The expert team, in their preliminary findings had categorised eight of the deaths as coincidental and linked only one to the vaccine. The health ministry suspended the use of pentavalent vaccine on October 23, after four deaths were reported.

According to the WHO letter, which was sent to the health ministry, on January 22, the drug regulatory authority (DRA) should send 85 vials to the Bangkok laboratory and 30 to France on February 1. The sample vaccines should be packed and sealed in the presence of officials from UNICEF, WHO and other health officials on January 31.

Health officials said the results would be known in about a month’s time. Meanwhile, the health ministry is yet to receive reports from the three experts, to whom the case history of the nine infants was sent, and from the lab in U.S., where the cerebrospinal fluid (CSF) was sent for testing.

By Sonam Pelden



No news on the vaccine front



23 December, 2009 - The health ministry is yet to hear from the center for disease control and prevention, (CDC), in Atlanta, USA, where a sample of the cerebrospinal fluid (CSF) was sent for testing a month ago as part of ongoing investigations into the pentavalent vaccine.

The CSF sample was taken from one of the eight babies that are suspected to have died after receiving the pentavalent vaccine. After a nationwide launch on September 1 this year, the vaccine was suspended for six months on October 23, following reports of suspected adverse effects.
Cerebrospinal fluid is the clear watery liquid that flows around the brain and spinal cord, surrounding and protecting them. Testing a sample of CSF, which is collected from the lower back, is helpful in diagnosing a variety of conditions affecting the central nervous system.

Health officials said that CDC, which is testing the CSF sample for free, is one of the best in the world. “We haven’t heard from them yet,” said the public health director, Dr Ugen Dophu.

CDC, according to press reports, is one of the 13 major operating components of the United States department of health and human services and a world authority on public health. The agency helped discover AIDS, Legionnaires’ disease, Ebola fever and Lassa fever.

A letter from the WHO’s South-East Asia regional office (SEARO) sent to the ministry on December 21 said that the preliminary report by the WHO team, who investigated the deaths, have been sent to three independent experts for analysis. “Once we receive the experts’ analysis, only then will the lab to test the vaccine samples be identified,” said the public health director. “They’ll also suggest the number of samples to be sent for testing.”

By Sonam Pelden


All articles from Kuensel on different dates