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Five years ago, the cost in some developing countries of testing each
transfusion of donated blood for HIV infection was estimated at $30, compared
with $1 allocated per person for health care in an entire year. Since then
the situation has improved slightly: a preliminary test on a sample of donated
blood can cost less than $1. But this is still a significant outlay for
countries where the annual health budget per person is only $2 or $3.

In industrialised countries, donated blood is now routinely screened
for HIV, making transmission by this route very rare. The same is not true
elsewhere. In Bombay, according to one speaker at a recent international
AIDS conference in Amsterdam, 172 out of a sample of 200 professional blood
donors tested were HIV-positive. They donated blood on average 3.5 times
a week, and 90 per cent had been doing so for more than five years. The
World Health Organization (WHO) estimates that in most developing countries,
between 1 and 5 per cent of new HIV infections are due to infected blood
transfusions, rising to 10 per cent in parts of sub-Saharan Africa.

When testing for HIV first began in the mid-1980s, the most commonly
used test was the enzyme-linked immunosorbent assay, or ELISA. Rosemary
Mwendapole, scientific officer in immunology at the Tropical Diseases Research
Centre in Ndola, Zambia, was involved in evaluating HIV tests for use in
26 hospitals and health centres there. ‘That is not a very user-friendly
test for developing countries,’ she says. ‘It’s all right for a well-equipped
laboratory, but the reagents are sensitive to heat and can go off very quickly.’
The test is laborious, involving adding many reagents and washing the plate
of test wells after each one. It is intended for batch-testing more than
90 samples at once, not one or two at a time, and takes two to four hours.

In the late 1980s, health workers in Africa began asking for test kits
that were not only cheaper, but also appropriate for use in small rural
hospitals and medical centres. Such kits would not rely on reagents that
needed refrigeration, would need no special skills to operate, could test
one or two people at a time rather than batches of up to 100, and give results
in a few minutes rather than hours.

These ‘rapid-simple’ tests are now on the market, though the majority
were intended for use in doctors’ surgeries in industrialised countries,
where patients would pay for an immediate answer. Many of them simply involve
adding a drop of blood to a well, followed by a few drops of different reagents,
and the result is available within a few minutes. Costs per sample range
from below $1 to $4. However, both Britain and the US have banned the
sale of such kits to private individuals to protect people from testing
without adequate counselling.

Few of these tests were designed with the needs of developing countries
in mind. One exception is a test being developed by Cambridge Biotech Corporation
in Worcester, Massachusetts. It uses the ‘latex agglutination’ method: tiny
beads of latex are coated with antigen proteins from HIV, making an initial
mixture that looks like normal milk. When the patient’s serum is added,
any HIV antibodies in it attach to the antigens, making the beads ‘stickier’,
until eventually they hook together into clumps. If a test of this kind
is positive, the final mixture will look like curdled milk.

The novel aspect of Cambridge Biotech’s test is how the latex beads
are agitated to bring them into contact with each other, an essential process
if they are to agglutinate in the presence of antibodies. A plastic slide
in the test kit is made from two pieces of plastic ultrasonically welded
together with a narrow, tube-like channel running through the centre. The
tester mixes the patient’s sample with the latex in a well at one end of
the slide, and drags the mixture to that end of the channel with a pipette.
Capillary action then draws the liquid along the channel towards the other
end of the slide, and so keeps mixing and agitating the beads. A result
takes five minutes.

The test can be read by eye, but to avoid errors, Cambridge Biotech
has developed a battery-operated slide reader small enough to fit into a
briefcase. This has a photodiode that can detect agglutinated particles,
and according to the result the reader displays a plus or a minus sign.
Cambridge Biotech says the test is very reliable, giving few false-negative
and false-positive results. The company plans to launch it in Europe and
developing countries this autumn. No price has yet been set, though the
slide reader will cost about $500.

Health workers who have used the test in Africa are enthusiastic about
it. Mwendapole says the test and slide reader are ‘simply fantastic. You
can take that little machine to the health centre, plug in the slide and
get your plus or minus.’

This method is ideal for screening donated blood, especially in areas
without blood banks where person-to-person donation is customary. Blood
that tests positive is thrown away and the donor told it is unsuitable.
However, if the person being tested is to be told the result, and the initial
test is positive, the small risk that it is a false-positive makes a second
and sometimes third test necessary for confirmation.

The WHO used to recommend carrying out an ELISA first, and then a test
called the Western blot. But while an ELISA costs only $0.75 to $1.75 per
sample, the Western blot (which requires nitrocellulose gels, radioactive
chemicals and photographic emulsions) is extremely expensive, at around
$40 each.

The new tests let the WHO change its recommendations. It now suggests
using specific combinations of the ELISA with rapid-simple assays to confirm
presence of HIV with maximum accuracy at the lowest cost (Weekly Epidemiological
Record, vol 67, p 145).

THE RIGHT PRICE

Most people working in the field agree that when used in these combinations
the rapid tests are simple and accurate. So now the problem is not devising
the technology for HIV testing in developing countries, but getting the
tests to those who need them, at an affordable price.

Both elements present difficulties. After supplies of test kits have
been imported, they can take months to reach outlying health centres, by
which time they may have already passed their ‘use-by’ date. As for cost,
John Parry, head of the retrovirus section of the Public Health Laboratory
Service in London, says: ‘The problem with finding a simple, self-contained,
rapid, robust, versatile, sensitive and specific assay for the developing
world is that there is a price to pay for each of these characteristics.
When you are demanding them all in one assay, that price is relatively high.’

Some companies charge higher prices to buyers in industrialised countries,
who thus subsidise those in developing countries. Patrick Leonard, chief
executive officer of Cambridge Biotech, says single-sample tests produced
by his company have been bulk-bought by governments and pharmaceuticals
companies and sold to developing countries for between $1 and $1.50 each,
while their price to developed countries ranges between $3 and $4. But
there is an inevitable floor to the price: apart from the cost of making
each kit, the development costs, licence payments and royalties must be
recouped.

Ingrid Van kerckhoven, who evaluates HIV tests for the Institute of
Tropical Medicine in Antwerp, a WHO Collaborating Centre on AIDS, says:
‘The rapid and simple assays are much too expensive. They can cost $4 or
$5 (per test). The only thing that most biotechnology companies are interested
in is the money.’

Supporters of this view highlight the WHO’s successful negotiation of
bulk purchase agreements which enable it to sell tests for $0.65 or $0.70
each – cutting the price by over 50 per cent. Further evidence that tests
can be produced very cheaply also comes from the Program for Appropriate
Technology in Health , a non-profit medical organisation based in Seattle.
In 1991 it developed a test that should cost about $0.20 and take 20 minutes
to give a result (¿ìè¶ÌÊÓƵ, 9 March 1991).

Milton Tam, PATH’s technical director of product development, says commercial
companies were not interested in producing such a test because they believed
it would produce an inadequate commercial return. But they may be mistaken
in thinking that the market for rapid-simple tests in the developing world
is a small one. Robert Downing of the Uganda Virus Research Institute, in
Entebbe, says there is a large potential market in Uganda among people who
want to know whether they are infected with HIV before marrying or starting
a family. But kits are not available on the local market, and many potential
users have trouble getting foreign currency. He thinks companies should
examine ways of distributing kits priced in local currency: many Ugandans
could afford to pay clinics or hospitals 2000 shillings (about $2) for
one-off tests, he says. It would up to the company to convert that money
back into dollars – easier in some African countries than in others.

With this in mind, PATH tried to set up manufacture of its test in Zimbabwe.
It was to collaborate with an African company in Harare, but the company
pulled out. ‘They had never manufactured diagnostics before,’ explains Tam,
‘so they needed substantial initial investment in expertise and equipment
and so on.’

The WHO supports initiatives such as that by PATH. Susan Holck, chief
of policy and planning at the WHO’s Global Programme on AIDS, says: ‘This
is one important way of trying to make test kits available at more affordable
prices.’ The WHO will help check the quality of locally produced test kits.

Although some private hospitals and clinics in developing countries
can afford to buy their own test kits and charge their patients for them,
many tests carried out in developing countries are paid for by grants from
research projects and international bodies such as the WHO. Mwendapole says:
‘Most people rely on projects that donate tests. The big question is whether
they will be able to carry on testing after those projects finish.’

The amount of attention focused on HIV has also brought other drawbacks.
‘A lot of them are still mouth-pipetting blood, and yet they have got nice
HIV-testing equipment, because HIV is what the donors are worried about,’
says Mwendapole. ‘What is the point of being able to screen the donated
blood for HIV if they don’t even have the equipment to establish if the
patient needs a blood transfusion?’

Sharon Kingman is a freelance journalist.