A killer on the wane

By Martin Johnston

Professor Diana Lennon had to abandon a study on meningococcal disease in March. Only a few children were catching the illness that has frightened parents and haunted hospitals for more than a decade.

It was to be the study to answer a key question left controversially unanswered so far by the Government's costly campaign to beat the disease; does it work?

"We were running a case-control study on vaccine efficacy in under-5s in the Auckland region," says Lennon, a Starship hospital paediatrician and the Auckland University researcher overseeing trials of the MeNZB vaccine. "That's been abandoned because we had so few vaccine-strain cases."

The scrapping of the trial encapsulates the twin dilemmas of the $222 million scheme to vaccinate more than 1 million people aged under 20 against the disease: how effective is the vaccine and would the epidemic, which has declined each year since its peak in 2001, end without immunisation?

Critics of the campaign say the epidemic was waning naturally, a notion the Ministry of Health rejects.

From 1991 to the end of last year, 5863 cases of all types of meningococcal disease were notified to health authorities; 238 people died and more than 1000 have been left with permanent disabilities such as brain damage or limb amputations.

Most, but not all, notified cases are now confirmed by laboratory tests. The rest are termed "probable" cases, based on the symptoms. Around 75 per cent of confirmed cases are of the epidemic version, a sub-type of the meningococcal B bacterium.

Others are caused by meningococcal C - 30 confirmed cases last year - or other strains.

Before the epidemic began in 1991, New Zealand had around 50 cases of all types of meningococcal disease a year. At its worst, in 2001, there were 650 cases. This dropped to 228 last year: 190 laboratory confirmed, including 113 which were of the epidemic strain.

Charlotte Cleverley-Bisman was one who paid a high price to the epidemic strain. Aged 7 months, the Waiheke Islander caught the disease in June 2004, a month before the start of the campaign that would become New Zealand's largest mass vaccination.

Her distraught family went public to urge parents to have their children vaccinated when the vaccine became available.

The illness swept through Charlotte with its characteristic lightning speed. She was flown by helicopter to Starship and her body went purple all over, just half an hour after the first spots were seen of the rash which indicated blood poisoning. Her body was shutting down. She needed a ventilator to breathe, blood transfusions and multiple drugs.

Parts of both her legs and both her arms had to be amputated and much of her skin was damaged - but she survived, and without brain damage.

Her father, Perry Bisman, describes Charlotte, now aged 2 years 8 months, as a happy, determined girl. But she is naturally frustrated at not being able do everything her peers can and she continues to suffer the effects of the disease in new ways: the remaining parts of her legs are growing at different rates, she is expected to need a wheelchair and she requires ongoing skin grafts.

According to the detective work of scientist Dr Diana Martin, programme leader on communicable diseases at the Institute of Environmental Science & Research (ESR), the epidemic strain probably arrived in New Zealand in 1990, several years after appearing in the Netherlands.

It quickly spread around the country, causing year-on-year rises leading to the epidemic's first peak, of 613 cases, in 1997.

Martin and her Dutch contacts began the search for a vaccine, work which took at least six years to come to fruition.

Vaccines existed for other strains of the disease - one was offered for a group A outbreak in Auckland in the 1980s - but none was commercially available for New Zealand's epidemic B strain, known to scientists by the name of a protein on its outer membrane called PorA type P1.7b,4.

Vaccines for strains other than B are made using the coating of the killed bacteria, but Martin says this is not possible for B group vaccines.

In 1998 the World Health Organisation arranged a meeting of New Zealand representatives and vaccine manufacturers but little progress ensued. The Netherlands produced a small quantity of experimental vaccine against the Dutch/New Zealand strain. A European trial proved it capable of producing antibodies - an immune response against the bacteria.

Cuba and Norway had developed vaccines for B epidemics in their countries, caused by different strains from New Zealand's epidemic strain. Cuba introduced its vaccine into its childhood vaccination schedule, bringing its epidemic under control; Norway did not carry out mass vaccination with its vaccine and its epidemic ended around 2001.

In the absence of a vaccine, New Zealand health authorities ran public campaigns to highlight the symptoms of meningococcal disease, urged parents to seek swift medical help, warned against "sharing spit" (as up to 30 per cent have the bugs in their throats without being sick), encouraged GPs to give antibiotics to suspected cases on their way to hospital, and commissioned research which linked the illness to overcrowding. The statistics had already shown it was more common in poor suburbs and particularly afflicted Maori and Pacific Island infants. Babies were the hardest hit.

Lennon says there was initially little progress on making a New Zealand-strain-specific vaccine after the WHO became involved, despite meningococcal disease having been identified as New Zealand's leading public health problem in 1996.

"The New Zealand Government wasn't acknowledging the problem."

But this changed after the 1999/2000 arrival at the ministry of Dr Lynne Lane, whom Lennon credits, as director of public health, with kick-starting the stalled search.

Meetings were held with the public health institutes of Norway, Cuba and other countries, but none had the capacity to make enough vaccine. The Cuban manufacturer's standards, which since met European and US requirements, were at the time considered inadequate by New Zealand. The Netherlands wanted to supply a six-strain vaccine but the ministry did not want New Zealand children given injections containing material from strains other than the epidemic version.

In 2001 the ministry chose California-based vaccine maker Chiron Corporation to develop Norway's vaccine for the New Zealand strain.

Clinical trials began in south Auckland in 2002 but, controversially, no phase three trials were held. Large phase three trials prove the effectiveness and safety (or ineffectiveness and risks) of a drug by comparing it against a placebo or existing medicines.

Vaccine authorities said phase three trials of MeNZB were unwarranted because they would have deprived the placebo recipients of the vaccine; 90 per cent of those given MeNZB could expect full protection based on the trials that were done. The parent Norwegian vaccine and related vaccines had been found to be safe and effective.

Publicity surrounding Charlotte Cleverley-Bisman and the death of 9-month-old Sakiusa "Junior" Uluvula from the disease created high expectancy before the start of mass vaccination in July 2004.

South Auckland and the Glen Innes area were the first to be vaccinated because of historically high disease rates. The three-dose programme rolled first north then south through the North Island, then northwards through the South Island. Preschoolers aged over 6 months were the first, then school children, followed by others up to age 19. In May last year the programme was extended down to 6 weeks of age and six months ago a fourth dose was introduced for babies.

Several months after the programme began, journalist Barbara Sumner Burstyn and researcher Ron Law - formerly a medical laboratory scientist who professes a "low regard for the medical profession" after years of reading medical literature - began criticising the ministry campaign in a series of magazine and internet articles and public meetings.

Law says it was a campaign of fear based falsely on the number of all cases, not just the epidemic strain. The $222 million "to try to prevent at most a handful of deaths a year" would have been better spent on improving housing.

He is proud to have dissuaded "10 to 15 per cent" of parents from having their children vaccinated and says he was never paid, "other than petrol money".

The ministry's director of public health, Dr Jane O'Hallahan, says 1 to 3 per cent were dissuaded and many of these later signed up. She says that level of indecision added a new burden for the campaign's front-line nurses. The public were badly served by the Sumner Burstyn/Laws views gaining a half share of some media coverage, when "99.9 per cent" of doctors supported the campaign.

The Government is claiming success for the campaign, both in vaccine uptake and in beating back the epidemic. The target was to vaccinate 90 per cent of those aged 6 weeks to 19 years. So far 80 per cent have had three doses. The rates are lower for 18 and 19-year-olds - and for Maori aged 1 to 4, who at 73 per cent are nearly 10 points behind the non-Maori-non-Pacific rate.

O'Hallahan says the most common reported bad reaction to the vaccine was a slight fever. One or two cases of severe allergic reactions were reported, a lower rate than for other vaccines. No deaths have been linked to the vaccine.

Vaccination remains on offer until December for those aged 5 to 19 years; after that it will be available for newborns and under-5s until 2009.

The key statistics the ministry relies on in asserting that the vaccine is killing - but has not yet killed - the epidemic are the reduction in epidemic strain cases in the Auckland-Northland region in the target age group: 84 in the year before mass vaccination started compared with 20 the year after. A 76 per cent reduction. Among Maori it is 90 per cent.

Law says the ministry graphs prove his point, that the epidemic was going away by itself.

The ministry argues that, based on the Norwegian experience, the epidemic could have lasted another 15 years and that the pre-vaccination reduction in cases from 2001's peak might have been another cyclical trough.

Martin "can't say" if the epidemic was waning on its own. She presumed the reduction in epidemic-strain cases last year was in part from vaccination; the trials, which started 18 months earlier may have helped in south Auckland too.

Lennon is more explicit: "There's been an effect from the vaccine and the continued natural waning of the epidemic. Certainly the drop in the epidemic strain in the south Auckland area ... has been dramatic in children under five."

Having scrapped what, in the absence of phase three trials, might have been the definitive study, Auckland University proposed a region-by-region review following vaccination to determine its effectiveness. The ministry liked the proposal, but awarded the study contract to Victoria University.

O'Hallahan would not reveal the study's latest findings, the "next best thing to a phase three trial", but says they are "extremely promising". The public will have to wait until July 24, when she releases them at a Chiron-hosted meeting in Siena, Italy, where the company makes MeNZB.

Get the news delivered straight to your inbox

Receive the day’s news, sport and entertainment in our daily email newsletter


© Copyright 2017, NZME. Publishing Limited

Assembled by: (static) on production apcf04 at 25 May 2017 20:58:48 Processing Time: 2722ms