On the trail of the killer that doctors forgot

In Britain it might keep your child off school, but in Malawi it is a killer. What turns a nasty virus into a deadly cancer? Geoff Watts reports on a medical mystery.

Scenario one. Peter, a teenager living in a comfortable British suburb, is fit, healthy and doing well at school. He wakes one morning feeling feverish, complaining of a headache. He has no appetite. His throat feels sore. The glands in his neck are swollen and tender, so his mother calls the health centre. The GP notices that Peter's armpits and groin are also swollen. A blood test confirms what the doctor already suspects: infectious mononucleosis, better known as glandular fever.

For a few weeks, Peter is off school feeling poorly. The doctor tells him there is no specific treatment but advises rest. Over the following two or three months, he has occasional bouts of depression and lethargy, but these eventually disappear. The incident - a tiresome milestone in teenage life - is closed.

Scenario two. Nyemba is younger than Peter and lives not in Britain but in a village in rural Malawi not far from Lake Nyasa. Nyemba can read and write, but his parents - subsistence farmers - are desperately poor. Their staple diet is mealie or corn flour. They have three other children, all with some degree of vitamin deficiency.

Shortly after his seventh birthday, a small swelling appears on the side of Nyemba's jaw. It grows rapidly. It is not painful, but his parents are worried. They take him to the village health worker who sends him to the local hospital. Nyemba has Burkitt's lymphoma, the commonest form of cancer in sub-Saharan Africa and certain to kill him unless he receives treatment very soon. There is no guarantee that he will.

You might imagine that these two case histories, so different in their circumstances and severity, would be entirely unrelated. Not so. They have something in common: a microbe known after its co-discoverers as the Epstein-Barr virus.

As head of the viral oncology unit at Imperial College School of Medicine, Beverley Griffin is interested in learning more about this virus and its peculiar ability to have such different effects in different settings. But her interest is more than academic. She has visited Malawi several times and seen its effects on children such as Nyemba, and she is keen to raise awareness of a problem that many people, including many doctors, wrongly believe to have been solved.

"From the mid-1960s, when the virus was discovered, through to the late 1970s there was an active programme of research," she says. "But because the tumour often responded to therapy, word got around that Burkitt's was not only curable, but had disappeared. It seems that when the people who did the early pioneering work retired, no one else picked it up. Burkitt's lymphoma was forgotten. I call kids with the disease Africa's forgotten children."

Notable among the pioneers was Dennis Burkitt, the English doctor who first described the disease in the 1950s. A lymphoma is the term for any tumour arising in the lymph nodes. The kind that Burkitt observed is mostly confined to sub-Saharan Africa. But even there its distribution is patchy. In Malawi it occurs in "hotspots", many of them areas close to Lake Nyasa.

It was in the early 1960s that English virologist Anthony Epstein and his colleagues found a previously unknown virus in a cell culture derived from a Burkitt's tumour. The same virus can also be found in cells taken from tumours of the nasopharynx, the region lying above the soft palate and behind the nose. This type of cancer is most common in southern China. Even now, Griffin says, we have to view the evidence linking the virus with these cancers as circumstantial. "We know that Epstein-Barr virus can cause cells growing in culture to proliferate and that almost all tumours can be shown to harbour it. But that is not the same as saying the virus must cause them."

It is clear that the virus does not act alone. Epstein-Barr virus is common in Britain, yet no one here gets Burkitt's lymphoma. It is common too in Africa, yet only a minority develop cancer. Even if having the virus is a necessary condition, it is not sufficient alone. Something else is involved. But what?

"We wish we knew," Griffin says. She points to five jars perched on the crowded bookshelves of her room in St Mary's Hospital, each labelled with a place and date. Their contents are bits of dried fish.

"The kids in the villages have a diet based mostly on corn meal, but they also eat fish. They are mostly the ones that are caught in the fishermen's nets but are too small to sell."

Could these fish be the answer? In the hope of detecting something suspicious, Griffin has had them analysed for the presence of chemicals known to cause cancer. The firm of analysts that is doing the work has, so far, found nothing conclusive.

Not that diet is the only possible link. "Malaria is probably involved because it depresses the immune system," Griffin says. "Also, Burkitt's is essentially a rural tumour, and it is a lower socioeconomic disease. When standards of living are higher, people do not seem to get it."

She suspects there may be a genetic component involved as well. Again the evidence is circumstantial, but Griffin believes it is significant that there is little inter-tribal marriage in the area of Malawi she has looked at. What a genetic factor might do is obviously a matter of speculation. It might damage the immune system and limit the body's innate capacity to deal with tumour cells.

The great frustration in all this is that most Burkitt's tumours respond well to one of the standard and cheaper anti-cancer drugs, cyclophosphamide. Treatment involves two or three courses of the drug over a month or so, with pauses to check for side effects. Because it needs to be given as a drip, with the attendant danger of infection, the procedure has to be done in hospital. Only two in Malawi - at Blantyre and Lilongwe - are suitably equipped. Malawi is a long, narrow country, so many patients have to make a lengthy and (for them) expensive journey. Add to this the difficulty facing a parent who has to be away from home, and it is not surprising that treatment is often unfinished, or that many children who suffer a recurrence are not brought back.

Treating cancer is never a priority in poverty-stricken developing countries. Even when funds are available, the drugs cannot always be obtained. And just a short delay may be disastrous because cell numbers in Burkitt's can double in just 30 to 60 hours, an extraordinarily rapid growth rate. That many patients are treated at all is a tribute to visiting doctors and scientists, some of whom bring supplies of drugs with them.

A couple of children's charities work with Burkitt's patients in Malawi. After drugs, says Griffin, it is money that is most needed.

Weighed against the many health problems in Africa, Burkitt's lymphoma is little more than a blip. But that is no argument for neglecting it - particularly when it is largely and quite cheaply remediable.