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PDF Vertigo : five physician scientists and the quest for a cure

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Warren Alpert Physician-Scientist MD/PhD and Advanced Training Program

As rhythmic sounds of drums and xylophones waft through the schoolyard, three or four students at a time lie on their left sides, heads on elbows, while screeners squirt gel onto their chests, press the wands over their hearts and pull up grainy grey images that show their valves opening and shutting. Some kids crane their heads to see the splotches of red and blue that indicate the direction of blood flow. Each screening takes about a minute. About 15 minutes into the session, a lean and muscular year-old boy in maroon shorts and brown boots stretches out on a table in front of Marco Costa, a gregarious cardiologist based at Case Western Reserve University in Cleveland, Ohio.

Thanks to years of trust-building work in the region, parents welcome the care. If the diagnosis is confirmed in the clinic, the family will then have the option of enrolling their son in the next stage of the trial. Overall, the trial has screened the hearts of more than , schoolchildren, reaching its goal of finding kids with early-stage rheumatic heart disease who can be enrolled into the next stage, being randomly assigned into one of two groups. Half will get monthly shots of penicillin, which is standard treatment for patients in advanced stages of the disease but which has never been tested during early phases, when heart damage has begun but symptoms of it have yet to appear.

The other group will get education and healthcare but not antibiotics. Should the treatment work — slowing, stopping or even reversing the progression of rheumatic heart disease by preventing further strep A infections and allowing the heart to heal — it will offer powerful justification for investing in screening programmes and distributing penicillin injections. A vaccine would be one such strategy.

The hunt for a strep A vaccine began nearly a century ago, at a time when the bacteria were wreaking havoc without discrimination across the world. Faced with a major public health problem, US scientists began conducting studies for a strep A vaccine.

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But by the s, despite some alarming outbreaks of rheumatic fever among US troops, improvements in sanitation and housing meant rheumatic heart disease was starting to decline. Widespread distribution of penicillin pushed numbers down even more. By the late 20th century, even as rheumatic heart disease continued to flourish in low- and middle-income countries, rates of rheumatic fever in the US had dropped to around 5 cases per , children.

But some US researchers never lost interest in developing a vaccine, says James Dale, chief of the Division of Infectious Disease at the University of Tennessee Health Science Center in Memphis, whose own quest for a strep A vaccine began in the s. Back then vaccine development was reeling from a major setback. In , a vaccine candidate had supposedly caused acute rheumatic fever in at least two kids enrolled in a trial to test it.

By the time the FDA lifted the ban in , rheumatic heart disease had mostly been forgotten by the public — though the US National Institutes of Health has been unwaveringly supportive of work like his, Dale says. But there is a scenario that might ignite that investment: a single vaccine that would work around the world, fighting off the many illnesses strep A causes and at all socioeconomic levels. If it could simultaneously prevent rampant skin infections in Fiji, sore throats in American schoolchildren and the cascade to rheumatic heart disease across low-income countries, it might be put on the list of recommended childhood vaccines — offering drug companies a reason to dole out the money needed.

After decades of advances and setbacks, the vaccine search is gaining speed. Partly this is because rheumatic heart disease is attracting fresh attention. There has been renewed effort to study the burden of the disease, while the World Health Organization, the World Heart Federation and the African Union have made fresh commitments to controlling it, as has the government of Australia, where the indigenous population suffers disproportionately.

At the same time, technological advances have helped a small, dedicated and close-knit group of researchers make new progress against a complicated enemy. There are over known types of strep A, distinguished by their unique M proteins — structures that sit on the bacterial cell wall like fuzz on a tennis ball. Our immune systems have to respond to the different M proteins, or M-types, by producing different antibodies. By adulthood, though, strep A infections become less common, suggesting that some immunity develops with age and that a vaccine could be feasible.

In low-income countries, a larger variety of types circulate. Types also vary from region to region, and even from one neighbourhood to another: a study in the Brazilian city of Salvador found a different distribution in slums than in wealthy areas. Around the same time, a research group started to collect M-types from across the world in order to work out which types circulate where and which are most responsible for infections, says Dale.

It now appears that M-types cause about 90 per cent of strep A infections, Dale says, and that they fall into about nine clusters. Immunity to one type offers immunity to others in the same cluster. Historically, attempts to develop a vaccine have focused on getting the body to produce antibodies to one M-type at a time. But the realisation that strep A can be grouped has opened up exciting possibilities. Using modern sequencing and computational techniques, Dale and his colleagues have developed a vaccine candidate that incorporates genes from 30 strains.

These account for 98 per cent of all cases of strep throat in Canada and the US, along with 90 per cent of cases of invasive strep A in the US and 78 per cent of invasive cases in Europe. Invasive conditions can strike anyone at any time, regardless of socioeconomics. In rabbits, the vaccine, called StreptAnova, has provoked the intended immune response. He now hopes to move on to testing the vaccine in its target population: adolescents, and then younger children.

And yet, decades later, it persists in poor countries. That failure to stop a preventable disease reinforces the need for a new approach. Due to the high volume of feedback, we are unable to respond to individual comments. Sorry, but we can't respond to individual comments. Recent searches Clear All.

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