Orders of the Day — Lariam

– in the House of Commons am 10:05 pm ar 12 Mawrth 1997.

Danfonwch hysbysiad imi am ddadleuon fel hyn

Motion made, and Question proposed, That this House do now adjourn.—[Mr. Ottaway.]

Photo of Ms Jean Corston Ms Jean Corston , Bristol East 10:07, 12 Mawrth 1997

I am grateful for this opportunity to raise a matter of urgent public health concern. One of the most remarkable phenomena of the past 30 years has been the increasing prevalence of foreign travel. People now travel to parts of the world that two generation ago were considered the preserve of the intrepid explorer. Before people travel, whether for holiday or business, they seek professional advice about endemic diseases in their country of destination and the medications or treatment that they should take—prophylaxis—to avoid contracting diseases. That is especially true of malaria.

Unfortunately, a more aggressive strain of malaria has emerged recently in some parts of the world, principally sub-Saharan Africa and parts of the far east. The previous prophylactics, chloroquine and paludrine were considered not to be effective enough. Another drug entered the market: mefloquine, which was marketed by Hoffman La Roche under the name Lariam.

I know someone in Bristol who took Lariam 10 months ago to travel to east Africa to finish some academic research. He was a highly competent professional and a married man with children. He was a young person with a great deal to give to the academic world. Just a few days after arriving in Nairobi, he collapsed in the street with total amnesia and was taken to hospital. He has since suffered psychotic attacks, and has had paranoid delusions and terror attacks. He cannot concentrate or work, and he cannot drive a car. His family life has been severely disrupted and he feels at the moment—at best—as though his life was on hold.

I have since discovered that he was not the only one. When he was in hospital in east Africa, he was told by a tropical diseases consultant that severe neuro-psychiatric side effects from Lariam were quite common. The consultant said that he saw hundreds of patients, and that the problem was that the symptoms could be diagnosed as a breakdown.

Following a BBC television programme last week in the west country, someone wrote to me to say that he had been a resident in east Africa, and now travelled there. When he was last in east Africa, he said, he consulted a doctor in the Nairobi hospital who is considered to be the leading expert on Malaria in Africa and he told me that NO doctor in East Africa will recommend Lariam as they all consider it highly dangerous. I told him my doctor had recommended it and his reply was that UK doctors do not know what they are talking about. I am in the medical business and in frequent contact with doctors and I have not yet found a single doctor in Africa who will recommend Lariam. As long ago as 1989, the World Health Organisation reported that mefloquine can cause severe mental disturbances, and that the reported side effects were a "cause for concern". Nothing to this effect was put in the product data sheet until 19 March 1996. Hoffman La Roche put out a press release on 16 March 1996 in which it blamed background depression as the cause of Lariam reaction. But the facts of acute neuro-psychiatric reactions in people with no previous history have been highlighted worldwide in many leading medical journals. The person I know certainly has no previous neuro-psychiatric history, and was an extremely fit young man.

I have since heard many instances of Lariam poisoning. An Officer of the House approached me last summer when I was tabling parliamentary questions on the matter to say that he knew a highly competent professional woman who had taken Lariam, who, he told me, was now psychotic. I have spoken to GPs who are very concerned. I met members of the Lariam support group, which is principally based in the west country but whose members come from all over the UK. I met a highly motivated young woman police officer, who has not been able to work for nearly a year and a half because of the serious side effects.

Lariam was made the drug of first choice in 1995 for sub-Saharan Africa and parts of Asia by the malaria advisory committee, which is headed by Professor David Bradley. It is also recommended as the first choice in MIMs, which gets its information from the malaria research laboratory of the Hospital for Tropical Diseases in London. The medical advisory service for travellers abroad also suggests Lariam as the first choice. British Airways travel clinic also recommends it on the basis of advice from MASTA.

On 7 October 1991, a change was made to the product data sheet with regard to the ability to drive. The recommendation was that such a task should be avoided for three weeks following therapy, because the patient may experience dizziness, a disturbed sense of balance or a neuro-psychiatric reaction. I do not know whether this is observed, and whether people who take that drug cease to drive a car for three weeks afterwards. I do not how people who go on fly-drive holidays manage.

It is interesting to ask what advice is given to travellers on the side effects. For example, somebody from the BA travel clinic said on the "Close Up West" television programme on the BBC: There are some possible side effects that have been experienced by some people. But surely people want to know how likely these are, how serious the effects might be, and how much testing has been done. On the BBC "Watchdog" programme, Dr. Peter Barrett—the MASTA director—said I have to say that personally I think I would probably tend to go for doxycycline in many of the areas where mefloquine might be used…I do find it difficult sometimes advising the use of mefloquine quite as widely. Many experts also argue that Lariam may not be suitable for two to three-week holidays.

I asked a series of parliamentary questions last June, and was told by the Department of Health that revised guidelines were still being developed by the malaria advisory committee and that no publication date had been set. I assumed that the MAC was a statutory body, but it turns out to be a self-selecting volunteer group of about 40 experts, which has met eight times since 1980. I asked again in early February when the committee would report, and was told by the Minister for Health that the consultation process was "taking longer than anticipated".

A leading figure in travel health in this country who is a member of the committee has told me that she is very impatient for the new guidelines to be published, so that she can advise practice nurses, who are often the people who talk to the traveller, and that she is keen to ensure that prophylactic drugs are taken far enough in advance so that any side effects can be ascertained. However, on BBC television on 6 March, Dr. David Bradley, the chair of the MAC, said: I have no idea when we will reach a consensus or whether we will reach one at all. It is safe to assume that there is a dispute about Lariam among acknowledged experts. The MAC held an emergency meeting on 25 March 1996, and it is right to ask whether that was because of increasing concern about neuro-psychiatric disorders. If that was when the committee last met, and if there has been no agreement nearly a year later, is the committee ever going to agree, and should not some other avenue be pursued?

It is important to ask what advice GPs give and what they say about Lariam. Dr. David Chisholm of the British Medical Association GPs committee, when asked whether he would take Lariam, said on BBC television: I would be reluctant to, because of the information that is reported to me and to all doctors about its safety profile and its side effects. Some of these side effects are serious and extremely unpleasant. It must be admitted that there are disputes about the prevalence of side effects. Hoffman-La Roche has always claimed that the rate of serious side effects, defined by the company and by the WHO as leading to death, prolonged hospitalisation or significant disability, as one in 10,000. Dr. Gordon Cook, an expert on malaria at the Hospital for Tropical Diseases, has described that as "sheer nonsense".

When doctors working at MASTA found that the number of their clients suffering from side effects seemed to belie the one in 10,000 assertion, they conducted their own trial, and found that one in 140 were so affected by Lariam as to make them temporarily unable to carry out day-to-day activities. Hoffmann-La Roche disputes those findings. Dr. Gordon Cook says that the MASTA figure is nearer the truth, but that personal experience leads me to conclude that the true prevalence is more than that". It would appear that wrangling over the definition of "serious" side effects may be another factor in the delay of the new guidelines that are awaited by travellers and all in the medical profession. My friend in Bristol would not be considered as suffering from serious effects according to the manufacturer, yet nearly a year later he cannot resume work.

A reply to a parliamentary question I tabled in July 1996 to the Secretary of State for Defence revealed that Lariam is not prescribed to service pilots and air crew, because of the possible side effects of dizziness or a distorted sense of balance. Furthermore, the Civil Aviation Authority has also stated that Lariam's significant side-effect profile makes its use in aircrew inappropriate. Surely that would lead a traveller on an aeroplane to ask, "If the pilot can't take it because it isn't safe, why should I be taking it? What is the pilot taking if he routinely flies to these areas, has stopovers and has not keeled over from malaria?"

As long ago as April 1992, the WHO removed mefloquine from the recommended anti-malarial drugs list for duty troops visiting high-risk malaria areas, on the basis of its concern about neuro-psychiatric side effects. What about people such as train drivers or brain surgeons, who have jobs in which they cannot afford to suffer dizziness, which require them to be in full command of their faculties? Those people go on holiday and take anti-malarial drugs, and the potential consequences are too awful to contemplate.

I am also concerned about the effects on children. Changes made to the precautions on the product data sheet in June 1993 included: a statement indicating that use in children below 15 kg is not recommended. However, a six-year-old girl died last year after suffering a severe reaction to Lariam, which she had been prescribed for a holiday in Nigeria. She developed a condition known as toxic epidermal necrolysis, which causes skin blisters and mucus in the eyes and nose. Her nails and hair fell out, and she died in intensive care.

Dr. Gordon Cook has said that Lariam appeared to cause an especially adverse reaction in young women. I do not know to what degree Lariam has been tested on young women, or any women. They are certainly given the same dosage as men, never mind the difference in their weight ratio, and I gather that the drug was trialled on Thai soldiers.

The statutory body that assesses data and gives product licences in the United Kingdom is the Medicines Control Agency. It also monitors and evaluates reports of suspected adverse reactions. It is worth drawing an analogy with something that was called to my attention when I served on the Select Committee on Agriculture, when we found that the veterinary medicines directorate gave product licences to organophosphate dips, and it had to monitor the suspect adverse reaction. That is asking people who guarantee the safety of a product to seek evidence that they are wrong. The Agriculture Select Committee recommended that those two functions should be separated because of potential conflicts of interest; a similar recommendation should probably be made in this case.

All the information that I have sought to date from the Department of Health regarding the number and nature of trials that have been done on Lariam before and since licensing has been refused, on the basis of section 118 of the Medicines Act 1968, on the restriction on disclosure of information. That section lays down that information supplied to the licensing authority in connection with the application for, and granting and maintenance of, a product licence or clinical trial certificate must be kept in confidence by the licensing authority and its advisory bodies.

However, a book published by the MCA in 1993 called "Towards Safe Medicines" says that section 118 is intended to protect the commercial secrets of the pharmaceutical industry. It says: But where there is a safety issue the necessary information is given because the need to protect public health takes priority. Interpretation of this section is kept under review in the light of developments in the EC Single Market to enable more information about the licensing process to be made public. An Internet trawl reveals adverse reactions and side effects reported from throughout the world.

There were three malaria deaths in the United Kingdom in 1990, and in the subsequent years there were 11, nine, four, 11, five, and 13 in 1996. The argument for retaining Lariam is based on the premise that the risk of not taking the drug are higher than those of suffering the side effects. There is anxiety that the MAC report may be being held up because of the concern that malaria deaths might increase in time if people do not take Lariam, but effectiveness must be balanced with compliance. If people suffer serious side effects, they will stop taking the prophylactic. Resistance to mefloquine is already being reported in sub-Saharan Africa and the far east.

This matter has the makings of a Government health scandal. The Government are awaiting a report from a non-statutory body, which has no obligation to report, and whose chair has cast doubt on whether it will do so. The Department of Health appears to be doing nothing while purporting to wait for others to act. The Medicines Control Agency appears to be sitting on its hands because it and the Department are responsible for a failure, first to organise and prioritise the conclusions to be drawn from research and monitoring, and secondly to ensure that those priorities and conclusions are unambiguously conveyed to the public via the organisations that I have mentioned.

The system does not appear to be working. Meanwhile, there is utter confusion and much misgiving over what advice to give travellers. There are arcane disputes over the severity of side effects. The manufacturers are involved in personal injury litigation. There are 1,000 litigants UK-wide; anyone who has practised law knows that personal injury litigation is a waiting game, and that is obviously unacceptable.

I congratulate the Lariam Support Group, some of whose members are in the Strangers' Gallery tonight. They are people who—

Photo of Mr Michael Morris Mr Michael Morris , Northampton South

Order. There is no one in the Gallery that the hon. Member and I are aware of.

Photo of Ms Jean Corston Ms Jean Corston , Bristol East

I apologise to you, Mr. Deputy Speaker. I am grateful to you for drawing that to my attention. It may be that people who have an interest in that matter will be listening intently to the debate.

These people have suffered terrible side effects and ill health after taking that drug, which they took in all good faith and on the basis of advice, sometimes for a very long time. Many of them are young, high-achieving people, who feel that their lives have been destroyed. They have suffered denial and, at times, disbelief. They have suffered the isolation of serious illness. They have been very brave in overcoming such adversity, and have joined to fight one of the giants of the pharmaceutical world.

It should not be left to them. I hope that the Minister's response tonight will give me confidence that some proper advice will be provided to people who must recommend prophylaxis for malaria, and that urgent steps will be taken to discover what it is about mefloquine that causes terrible side effects in so many people.

Photo of John Horam John Horam , Orpington 10:24, 12 Mawrth 1997

I congratulate the hon. Member for Bristol, East (Ms Corston) on raising this matter, because it enables us to discuss two very important public health issues: the prevention of malaria and the safe use of medicines. Lariam—which is otherwise known by its approved name, mefloquine—is one of several medicines used in the prevention and treatment of malaria. It has an important place in medicine, although, as the hon. Lady has made clear, its use may lead to adverse reactions.

The starting point for this debate should be a recognition that malaria is a serious disease that can lead to death. It is a major cause of ill health and death in many parts of the tropics and sub-tropics, and effective prevention of malaria is a concern to anyone who travels to areas where it is endemic. Malaria is a parasitic disease, which is transmitted by the bite of an infected mosquito. Of the four types of human malaria, falciparum malaria is the most serious.

The symptoms of malaria may include fever, chills, sweats, coughs, diarrhoea, respiratory distress and delirium. However, these can be very varied, and malaria can easily go unrecognised and be misdiagnosed. Falciparum malaria leads to bleeding disorders and failure of various organs. It may also involve the brain, leading to coma and death. Prompt treatment of malaria is essential, even in mild cases, since irreversible complications may develop rapidly.

In the United Kingdom, malaria is an imported disease. About 2,000 cases a year are reported to the public health laboratory service malaria reference laboratory, and, as the hon. Lady said, between four and 12 people a year have died of it in recent years. An increasing proportion of cases is due to the more severe falciparum malaria, which currently accounts for about 60 per cent. of the total.

The Government have long recommended that all travellers to malarious areas take appropriate measures to protect themselves against malaria. Travellers to the tropics and sub-tropics should consult a doctor before travelling. We issue recommendations on malaria and its prevention, both to the general public and to doctors.

Advice for the public is contained in the free booklet, "Health Advice for Travellers" and in a new leaflet on malaria, both produced by the Department of Health. That advice is kept up to date, and is also available on Prestel and Ceefax. The United Kingdom Health Department's book "Health Information For Overseas Travel", which every general practitioner receives, contains more detailed information for doctors. Additionally, the malaria reference laboratory has pre-recorded information on malaria prophylaxis for travellers. and provides advice on specific problems to healthcare professionals.

Prevention of malaria in travellers consists of four components: first, awareness of the risk in the area visited; secondly, preventing mosquito bites by the use of insect repellants, protective clothing after dark and sleeping under bed nets; thirdly, taking an appropriate medicine regularly throughout the stay and for four weeks after returning; and, finally, remembering that malaria can still occur despite all these precautions, and seeing a doctor urgently in the event of fever or flu-like symptoms for up to a year after returning.

As the hon. Lady said, there are several medicines available that protect against malaria, and a range of alternatives is needed, because the disease varies from one part of the world to another. This depends on the type of malaria that is predominant, and on whether local malaria parasites are resistant to particular medicines—a problem that has increased in recent years. In many countries, falciparum malaria is now resistant to chloroquine, which has been the mainstay of malaria prevention for many years.

Advice on the prevention and treatment of malaria has been provided by an ad hoc committee convened by the malaria reference laboratory. The committee's guidelines, which are aimed at health professionals, were last published in the British Medical Journal in 1995, where they are available to all those interested in the subject. Its report includes advice on the use of mefloquine.

The committee is presently producing a new set of guidelines. When consultation has been completed, its advice will be published and the Government will review the implications fully. I heard clearly the hon. Lady's impatience with the procedure. I take her comments seriously, and I shall determine when the committee intends to conduct a further review or publish work on the subject.

Once licensed, the Government closely monitor the use and adverse effects of medicines to ensure that experience from widespread use is appropriately acted upon. This work, which is called pharmacovigilance, is a top priority for the Medicines Control Agency, and an area where the UK is a recognised world leader. Our record in identifying unexpected drug safety hazards, investigating them thoroughly and taking effective and prompt action is second to none.

The yellow card scheme encourages doctors to submit reports of adverse effects to medicines to the MCA through one of the best supported reporting schemes in the world, underpinned by a purpose-designed, state-of-the-art computer system. This scheme enables us to identify important hazards as early as possible.

The Government also use a range of other methods to assess adverse drug reactions, so that effective preventive measures may be put in place. The UK has taken a lead by developing the methodology of, and guidelines for, formal post-marketing surveillance studies, and by using databases such as the general practice research database for the investigation of possible drug safety hazards.

Mefloquine is an anti-malarial drug derived from quinine, which was first authorised in the UK in 1989. It has a high level of effectiveness—between 90 and 100 per cent.—in both preventing and treating malaria. Mefloquine is an important anti-malarial drug because it is useful in areas where the parasite is resistant to other drugs, notably chloroquine.

As with any medicine, the safety of mefloquine depends on appropriate use, but adverse effects may occur even when it is used as recommended. The authorised product information for mefloquine describes the recommended uses, provides dosage schedules, indicates who should not use it, and sets out the precautions necessary for safer use, and lists the recognised adverse reactions. This is available to both doctors and patients, in the latter case supplied with the medicine in lay language. Perhaps it is not plain English, but it is understandable lay language.

The most important adverse reactions to mefloquine are those affecting the nervous system—the so-called neuro-psychiatric reactions. The most common are depression, headache, anxiety and panic reactions. When relatively mild, these reactions are distressing to the user and his or her companions, and may curtail their trip abroad. Fortunately, most such reactions are mild and short-lived, and do not lead to serious consequences or a need for hospitalisation. Rarely, neuro-psychiatric reactions are serious or more prolonged, and no one is underestimating the consequences of such reactions for the individuals concerned.

We must see the problem in its proper context. First, travellers to tropical and sub-tropical regions face an important risk of malaria, which is an illness with significant morbidity and mortality. Secondly, used correctly, mefloquine is highly effective in preventing malaria, and where there is resistance to chloroquine, it is the best treatment available. Finally, alternative anti-malarials are also associated with adverse effects, and these may also be serious on rare occasions. Overall, the balance of risks and benefits for mefloquine is favourable, and similar to alternative treatments.

Adverse reactions to mefloquine have received considerable publicity in the media, and it is right that the public should be aware that medicines may have important side effects. It is unfortunate, however, if the messages provided are not well balanced, as this may unjustifiably scare the public and lead them to take inappropriate action, such as stopping medication needed to prevent malaria. For travellers to endemic areas who do not use preventive medicines, the risks and consequences of contracting malaria are much greater than the risks of serious adverse reactions occurring with mefloquine.

The hon. Lady mentioned the number of adverse reactions. About 1,200 people are reporting possible adverse reactions in any one year. It is probable that 700,000 have taken the drug. The MCA and the committee on the safety of medicines have carefully monitored the safety of mefloquine since it was authorised in 1989. In the light of accumulating experience, product information has been amended on no fewer than five separate occasions to make 16 significant changes to the recommendations on its use and safety. That should ensure that doctors and patients are fully aware of the adverse effects of mefloquine, and know that appropriate action can be taken to minimise them.

An important further change is currently being made to recommend that people start a course of mefloquine up to two to three weeks before travelling. The effect will be that most patients who do not tolerate it will be aware of the problem before they travel, and will not experience difficulties in unfamiliar surroundings.

We have also provided doctors and pharmacists with information and guidance about neuro-psychiatric adverse reactions, in an article published in the bulletin "Current Problems in Pharmacovigilance" in July 1996. That followed a review initiated by the Committee on Safety of Medicines. Safety monitoring is a continuous process, and, as with any medicine, further action will be taken as and when new evidence becomes available that has an impact on the risks and benefits of the drug.

I assure the hon. Lady that I was impressed by what she said. I take it seriously, and I will monitor the situation in the light of it.

Question put and agreed to.

Adjourned accordingly at twenty-five minutes to Eleven o'clock.