Travel vaccines no passport to safety

The first of a two part special report on the real effectiveness and dangers of the major travel vaccines and the best alternatives.

Government policiy for travellers abroad appears to be a case of massive overkill. A handful of vaccines are urged and sometimes even forced on you anytime you venture much beyond our shores. If you were to listen to the UK Department of Health's recommendations "Health Advice for Travellers" or the Center for Disease Control and Prevention in the US, you'd get vaccinated against polio every time you stepped foot outside Europe, North America or Australia, even though the disease is virtually non existent in many of these recommended areas.The problem with this "just in case" mindset is not only that it creates a paranoic view of the world, but also that it offers travellers a false assurance that a simple jab can take the place of careful precaution when heading off to remote areas. Furthermore, it rests on the assumption that these jabs actually work. Of all the vaccines, travel vaccines have the poorest record of success. The old cholera vaccine has such a dismal track record that it may be one reason the World Health Organization (WHO) has dropped it from the list of required immunizations and no country requires it anymore.

With malaria there is not only no vaccine, but a dangerous and growing resistance to the drugs used to treat it.

With travel vaccines, more than any other, it's vital to find out how necessary, how safe and how effective each one is, even before you make your travel plans, particularly to less well trod areas. Here, in the first of two parts, are the available studies to date about malaria, cholera, typhoid and yellow fever.

Malaria

Of all infectious diseases abroad, malaria is perhaps your greatest risk. WHO estimates that there are 300-500m people infected with malaria, the parasitic disease carried by the Anopheles mosquito (JAMA, 1996; 275 (3): 230-233). Each year in Britain, 2000 people contract malaria and 12 people die, a higher figure than from any other tropical disease. (In America, where presumably fewer people travel to Asia and Africa, several hundred patients contract it every year.) There is no reliable vaccine for malaria, so the rationale has been that taking the drugs which treat malaria as prophylaxis (just in case measure) before, during and after your stay in the infected area will also somehow ward off the disease.

Several synthetic drugs developed during World War II to be taken against malaria used to be effective. The problem is that most strains of the disease have developed active resistance to the drugs. Few tropical countries are now unaffected by strains resistant to chloroquine, often used with proguanil (Paludrine), the former drugs of choice; resistance to quinine, an earlier favourite, is also now increasing. Consequently, doctors and even tropical vaccine experts are finding it difficult to tell patients which types of drugs work where any more. They tend to rely on a quick change scheme of swapping schedules of drugs frequently in the hope of outwitting resistant strains. The same applies to patients who return with malaria; the choice of treatment depends on the parasite's resistance to the drug in the area where you got the infection (New Eng J Med, 1996; 800-6).

The general rule of thumb at the moment is to use combinations of drugs in areas where resistance is known not to be high (BMJ,1993; 307: 1041; New Eng J of Med, 996; 335: 800-6).

There is also the fragile balance which must be maintained between the risk of the disease and the risk of the drugs. There are a number of toxic effects with all these drugs, such as nausea, vomiting, severe gastrointestinal disturbances, and even psychotic reactions. Chloroquine can cause bone marrow suppression, heart problems, a neuropsychiatric syndrome and brain dysfunction. The British Compendium of Data Sheets 1996-7 also lists skin eruptions, itching, hair loss and skin depigmentation. Prolonged high doses of chloroquine can lead to damage to the retina of the eyes, ringing of the ears or convulsions. One doctor reported that his 6 year old son had a grand mal seizure after taking the drug (BMJ, 1996; 312: 1421).

Other sulphur drugs such as sulphadoxine purimethamine are effective but also cause rapid development of resistant strains (The Lancet, 1996; 347: 244-8).

The natural compound quinine, made from cinchona bark, remains more than 85 per cent effective nearly everywhere and has been a mainstay of malaria treatment for three centuries. Nevertheless, it is starting to lose its effectiveness in Southeast Asia.

It also can be toxic, causing dysphoria, tinnitus and high tone deafness, hypoglycemia and even serious cardiovascular or nervous system effects (New Eng J Med, 1996; 335: 69-75 and 800-6).

As drug resistance grew, so tropical disease experts turned to mefloquine, marketed as Lariam by Swiss pharmaceutical giant Hoffman-La Roche. Besides its effectiveness, this once a week anti malarial quickly became popular because of its convenience (The Lancet, 1996; 348: 344). However, because it tends to stay in the system for a long time, the potential for adverse reactions also appears heightened (see box below). And now holfantrine is being looked at as a possible new drug, although there is evidence of toxicity of the heart (Lancet, 1993; 341-1044-49).

Another problem is the potential for drug interactions between the drugs, particularly as more than one are often taken (New Eng J Med, 1996; 335: 800-6).

Many hopes had been pinned on trials of SPf66, a new vaccine developed by a team in Colombia. After a series of studies, protectiveness was found to be only 31 per cent, but was nevertheless considered encouraging (The Lancet, 1994; 344: 1172-3). However, a later randomized double blind trial study of infants in the Gambia showed that the vaccine was useless, as did a study of children in northwestern Thailand (Lancet, 1995; 346: 462-7 and 1996; 348: 701-7).

Thechances of getting malaria varies a great deal from area to area, and it also depends on when and how you travel.

Travellers to Africa are at risk in most rural and many urban areas, particularly during the evening. Most travellers to Asia and South America, however, spend most of their time in towns or resorts where there is limited, if any, risk of exposure, and they travel to rural areas mainly during daylight hours when there is also limited risk of infection.

Cholera

Cholera (Vibrio cholerae) infection is caught from contaminated food or water and usually results from poor sanitation. In a 1991 epidemic in Peru of over 16,400 cases and 71 deaths, the epidemic was traced to drinking unboiled water, or water from a household water storage container (Lancet, 1992; 340: 28-33).

Cholera vaccination is no longer recommended for the current outbreak in South and Central America. There have been some instances in African countries where a vaccination certificate has been requested at the border, but this is not common. In any case, cholera doesn't appear to pose a serious threat to Britons, since only about 30 contract it every year, according to the Public Health Laboratory Service. Risks are higher in America, with its proximity to South America, where 10 cases were reported in only three states, following the big epidemics in South and Central America in the early 1990s (JAMA, 1991; 265: 2658-9).

The main reason for dropping the recommendations could be tacit admission that there is no effective vaccine to date. The killed injected vaccine, which offered protection (if at all) for only a few months (Ind J Biochem & Biophys, 1994; 31: 441-8), is now being replaced by a number of whole cell and live vaccines. Some studies of the killed oral WC/rBS vaccine were promising, showing a protection of 85 per cent after six months, but largely among patients with type O blood (Lancet, 1994; 344: 1273-6). A 1993 Vietnamese trial of the killed oral cholera vaccine showed an effectiveness of only 60 per cent, leading doctors to experiment with a single dose of the live oral CVD vaccine. Nevertheless, experience demonstrated the vaccine only offers protection against certain strains (Lancet, 1997; 349: 957 and 1992; 340: 689-93). It's known, for instance, that the vaccine doesn't protect against a new strain, known as Bengal cholera, that has emerged in southern Asia.

In July 1994, in one of the worst cholera outbreaks in recent times, 12,000 Rwandan refugees died in Goma (eastern Zaire). This strain was also resistant to tetracycline and doxycycline, used to treat cholera (JAMA, 1996; 276 (5): 348). Other multiple drug resistant strains have emerged in Honduras (Lancet, 1997; 349: 924).

Besides fever, you can experience serious allergic reactions to this drug, nerve damage, and even mental problems (Infection & Immunity, June 1996; 64 (6): 2362-4). In one study, cholera vaccine may be responsible for transverse myelitis (J Royal Society of Med, 1990; 83; 653).

Other studies have shown pancreatitis (Br J Clin Pract, 1986; 40: 300-1); hepatitis B (Presse Medicale, 1986; 15: 1331); immune complex disease (Trans Royal Soc Trop Med & Hygiene, 1984; 78: 106-7); stroke (Lancet, 1985; 2: 1372); sudden death (Forensic Science Inter, 1984;

24: 95-8); myocarditis (Deutsche Med Wochenschrift, 1984; 109: 197-8); and psychiatric complications (Acta Neurological, 1974; 29: 520-33). Occasionally side effects are heightened when cholera has been given with typhoid vaccine (Beitrage zur Pathologie, 1976; 158: 212-24). The live (oral) form is purported to have fewer side effects (BMJ, 1993; 307: 1425).

Simply obeying certain hygiene rules, particularly concerning water and uncooked food, and replacing lost fluids may protect you against all forms of cholera; studies have shown that a healthy person can have more than a billion cholera bugs in their body without developing the disease (Times, June 3, 1993).

The most important element is to avoid the effects of severe diarrhea, which is what eventually kills you. A patient with cholera can lose virtually twice their weight in fluid in a single day (see Alternatives, p 6, for tips on rehydrating after diarrhea).

Some data has suggested that getting cholera and yellow fever vaccines simultaneously will decrease the response of both. Although this data is disputed, Wyeth-Ayerst, who produce the injected cholera vaccine, recommends that each be given in no less than a three week interval of the other.

Typhoid

Typhoid fever (caused by Salmonella typhi) is also spread by contaminated food and water. In Britain, some 200 people come home from holiday each year with typhoid. Typhoid vaccine is recommended for those travelling to areas where they may be exposed to contaminated food and/or water, particularly where the disease is common or sanitation particularly primitive. In practice, if you follow the lists put together by the Department of Health, you can end up getting shots even if you are heading off for a first class holiday in the Caribbean.

The heat phenol inactivated injected whole cell shot has an effectiveness rate of 65 per cent but causes severe adverse reactions in one quarter of patients (Infect Control & Hosp Epidemiology, 1991; 12: 168-72).

The typhoid vaccine should not be used in children under one year, and its harmful effects are worse in people over 35. The interaction of the fever (caused by the shots) and an underlying heart condition can cause shortness of breath, dehydration and fever (Washington Times, February 23, 1993).

Pasteur Merieux's new live Typhim VI vaccine, a polysaccharide vaccine, is purported to work better and cause fewer side effects than previously available vaccines (Military Medicine, 1990; 155 (6): 272-4). In practice, this means an effectiveness rate of between 64 per cent and 81 per cent in countries where the disease is endemic (GP, May 22, 1992). The manufacturer warns that Typhim's effectiveness could be lowered if you have an immune disorder or are already receiving treatment that lowers your immunity. As with any vaccine, if you've already had a severe reaction to Typhim VI you should not receive it again, and it shouldn't be administered to children over 6 (Infec Con & Hosp Epid, March 1991; 12 (3): 168-172).

Side effects from the oral vaccine include abdominal discomfort, nausea, vomiting, fever, headache, and rash. The most common side effect from the injection is redness, hardening and tenderness in the skin, which occurs in most patients. Fever, nausea, headache and flu like symptoms have been reported in 8 per cent of patients. People who receive the shot have fewer side effects if it is given into the skin (ie, intradermally), rather than under it (J of App Phys, June 1992; 72 (6): 2322-8). Other reports of side effects include loss of consciousness, abdominal pain, vomiting, hypotension, arthralgia, kidney problems, neutropenia (lowering of blood cells) and allergic shock.

Yellow Fever

This is a well known disease that has plagued the tropics relentlessly. Yellow fever is a viral disease transmitted to humans by mosquitoes. You may not be able to avoid it if you are travelling to certain parts of Africa or South America, since you need a certificate of vaccination upon entry. The vaccine must be given at least 10 days before entering a country requiring it.

If you are dead set against the shot, it may be wise to avoid any areas requiring the certificate. Eastern and southern African states have hitherto been free of epidemic yellow fever, hence routine vaccination is not a policy in these countries.

On paper, the shot seems effective. In one study, the shot produced antibodies in 93 per cent of adults (J Biol Standards, 1986; 14: 289-95), although this fell to 60 per cent in babies (W Afr J Med, 1990; 9: 200-3).

This vaccine, which is given live, can cause encephalitis (inflammation of the brain), especially in children under nine months, although a four year trial among pregnant women and its effect on their newborn children showed no significant side effects (Transactions of the Royal Soc of Trop Med & Hyg, May-June 1993; 87 (3): 337-9).

The vaccine has also been shown to cause urticaria, bursitis, jaundice, neurititis, myalgia and low grade fever. About a quarter of patients react, and 11 per cent suffer post vaccine syndrome of multiple pains and fever (Bul Soc Path Exotique et de Ses Fil, 1986; 79: 772-6). In one African study, a number of patients developed gangrene of the arm just a few hours after being inoculated at Shaki, Nigeria in May, 1987 (Revue Roumaine de Virologie, Jan-Jun 1994; 45 (1-2): 25-30). Five went into a coma and died. Nevertheless it may have been that poor hygiene and possible contamination played a part.