|
|
|
|
|
|
A
native of South Africa, Keith Klugman remains committed to improving
health conditions there. His landmark pneumonia vaccine study of
South African children concluded that the pneumonia vaccine could
save thousands of lives. |
|
|
|
|
|
SOUTH AFRICA is a place of
contradictions—extreme natural beauty and stark urban landscapes,
an infrastructure as modern as any in western Europe in some places
and conditions as primitive as the poorest countries in others. |
|
|
|
|
|
The
incongruent, sometimes surreal nature of things in South Africa
shaped Keith Klugman, a physician and microbiologist born and raised
there. Growing up in Johannesburg could offer anyone a unique perspective
on disease and disability in the developing world. And Klugman,
the world’s premier expert on antibiotic resistance among
pneumococcal bacteria, has put his insider knowledge to good use
on the world stage. Recently named the first William H. Foege Professor
of Global Health at the Rollins School of Public Health (RSPH),
Klugman is a prolific scientist, a mover and shaker on the international
public health funding scene, and a congenial fellow on top of it
all.
Even though he now lives and works
in Atlanta, he never loses sight of what developing countries are
up against in their often losing battles against death in children.
So many young South Africans die every year of respiratory infections
that he decided to make preventing and treating those infections
his life’s work. The AIDS epidemic has made this work more
important than ever.
“Pneumonia is a big problem
at the extremes of life everywhere in the world,” he says,
“but it is astonishing in South Africa. Plotting age against
incidence of pneumonia typically produces a U curve. But now in
South Africa, the curve is like a W, because of the huge burden
of HIV. Huge numbers of people are dying of AIDS-related pneumonia
at the prime of their life, and because of it, the average life
expectancy is dropping into the 30s.”
From 1995 to 2000, Klugman served as director of the South African
Institute for Medical Research, the country’s parallel agency
to the CDC. In 2001, he decided to plant his flag at Emory.
“His presence has placed our
school at the cutting edge of infectious disease research in Atlanta
and around the world,” says Dean James Curran. “A real
scientific force, he has more than 300 publications in major peer-reviewed
journals, and his studies are supported by many government, foundation,
and industry sources. He is a world leader and is helping make our
school a world leader as well.”
Leaving the top public health job
in South Africa was largely a matter of politics, says Klugman.
“Like our current CDC, South African health agencies have
become more politically oriented, and the top job became a political
appointment. The government in South Africa decided that the head
of it should be a financial business person rather than a scientist.
So there was a parting of the ways. I decided to retain my research
unit in South Africa but look for opportunities in global health
internationally.”
Klugman remains deeply committed to
improving health conditions in South Africa. He maintains a cohort
of almost 40,000 children in Soweto and directs the University of
Witwatersrand Respiratory and Meningeal Pathogens Research Unit
in Johannesburg. Although he returns often to South Africa for work,
coming to Emory has given his work a more global reach.
He travels literally around the world several times a year. Klugman’s
latest trip took him to South Africa, China, and then London for
an interview for the BBC and a meeting with the Wellcome Trust,
for which he chairs the Tropical Interview Committee. |
|
|
|
|
|
|
|
|
|
SELLING
HARD SCIENCE |
|
|
For
many years, the president of South Africa denied that HIV causes
AIDS, and a clear “anti-science bias” emerged within
the government. Although the climate is improving, thanks to lawsuits
brought by HIV-infected people demanding treatment, the place where
politics and science intersect remains murky in South Africa. Klugman
was recently mystified, but not too surprised, by a letter thanking
him for his services to a South African government vaccine advisory
group but notifying him that the group was being dissolved. The
news came on the heels of Klugman’s landmark pneumonia vaccine
trial published in 2003 in the New England Journal of Medicine.
The study of almost 40,000 South African children concluded overwhelmingly
that the pneumonia vaccine could save thousands of lives among HIV-positive
as well as HIV-negative children.
“Vaccine use must be directed
by good science, and developing countries like South Africa with
a high burden of disease have enormous challenges to meet,”
Klugman says. Once people are sick, diagnosing and treating pneumonia
can be expensive, requiring tests like X-rays not readily accessible
in developing countries. Lack of access to diagnostic tools is a
key barrier to appropriate care, he says. |
|
|
|
|
|
|
|
|
|
He
is a member of an international group of researchers who recently
received a Grand Challenge grant from the Bill and Melinda Gates
Foundation. The program seeks creative, yet scientifically sound
solutions to obstacles to overcoming disease and death in developing
countries. The proposition submitted by Klugman and his colleagues
was among 43 selected out of more than 1,500 submitted by scientists
in 75 countries. The group hopes to design an end point for clinical
trials that would act as a substitute for more expensive vaccine
trials for prevention of pneumonia.
Since the leading cause of pneumonia
is pneumococcus, Klugman wondered if prevention of carriage of the
organism in the back of the nose in young children might indicate
vaccine-attributable prevention of pneumonia. “We wanted to
work out whether just demonstrating the impact of vaccine on carriage
could be a surrogate for demonstrating protection against pneumonia.
Our group and others are conducting new studies to define the relationship
between carriage of pneumococci—in which a person carries
the bacteria in the back of the throat but isn’t sick—and
the development of pneumonia. So far, it seems that carriage is
a necessary precursor to invasive disease. It could well be that
the impact of the pneumococcal vaccine on pneumonia is through its
ability to protect against carriage.”
Why the normally benign physiologic
state of carriage leads to pneumonia is another question Klugman
is seeking to answer. “We have really good evidence that viral
infections such as influenza can upset the immunologic balance that
keeps the bacteria in check,” he says. “If pneumococci
are present, then influenza can allow the bacteria to invade. It
does this in many ways but mainly seems to disrupt the integrity
of the epithelial lining of the back of the nose, making it vulnerable
to bacterial invasion.”
Klugman’s paper in the August
2004 issue of Nature Medicine shows that the new pneumonia vaccine
decreases the number of severe influenza-related hospitalizations
among young children. Some people die of the actual influenza viral
infection, but a large proportion of deaths stem from the secondary
bacterial infections that follow influenza. “So this paper
showed that children who got the pneumococcal vaccine had less influenza-related
pneumonia,” says Klugman.
The study showed that a nine-valent
pneumococcal vaccine prevented 31% of pneumonias associated with
any of seven respiratory viruses. It thus confirmed a role for the
pneumococcus in virus-associated pneumonia. |
|
|
|
|
|
|
|
|
|
COMPLICATING
MATTERS |
|
|
HIV
infection, however, drives the incidence of pneumonia out of kilter
everywhere in Africa, and particularly in South Africa.
“Even in communities where HIV
is very common in adults and even where there are programs to halt
transmission from mothers to children with the use of antiretroviral
drugs during pregnancy, you still get about 10% transmission, so
at least 3% of all kids born are HIV infected,” says Klugman.
That small fraction of children carry
such a huge burden of pneumonia that the total burden of pneumonia
has increased about three-fold in the community at large because
this group of children has 100 times increased risk of getting pneumonia.
“That’s a 300% increase in the burden of pneumonia in
the community,” says Klugman.
“In our vaccine trial we found
that the pneumococcal vaccine prevented pneumonia in HIV-positive
and HIV-negative children. That was a landmark finding and establishes
a good foundation for inoculating all HIV-positive children with
the pneumococcal vaccine.”
And HIV amplifies the need for all
measures to prevent infectious disease. |
|
|
|
|
|
|
|
|
|
Klugman’s
work to prevent pneumonia through vaccines also includes a vaccine
to protect against Hemophilus influenzae type B (HIB),
the second leading cause of pneumonia in children in developing
countries. This vaccine is commonly available in the United States
and other western countries but is largely unavailable in the developing
world. “I’m trying to find strategies for both of these
vaccines to be more affordable and to be introduced more rapidly
into developing countries,” he says.
Surveillance of infectious diseases
is another important area of Klugman’s work. “Infectious
diseases are pliable—they can change and adapt, as in the
case of antibiotic resistance. There is also the real threat of
new emerging infections,” he says. “We must help developing
countries develop the capacity for surveillance. My research unit
in South Africa pioneered surveillance for a lot of important diseases
including pneumococcus, HIB, and Neisseria meningitidus,
which is the third leading cause of meningitis. We also have surveillance
there now for opportunistic infections such as cryptococcal disease—a
severe kind of fungal meningitis particularly associated these days
with HIV infection.” |
|
|
|
|
|
|
|
|
|
LEVERAGING
PUBLIC RESOURCES |
|
|
Now
that solid infectious disease surveillance programs are established
in South Africa, Klugman hopes to spread them to the rest of the
developing world. In July 2005, he was appointed chair of the International
Committee of the American Society for Microbiology (ASM), a group
with more than 40,000 members and a large full-time staff in Washington,
D.C. He hopes to leverage this role to increase surveillance capacity
and improve training for microbiologists in developing countries.
For example, the ASM recently collected more than $30,000 to boost
infectious disease surveillance in the wake of the tsunami in Banda
Aceh, Indonesia.
No matter where Klugman goes, he knows
that politics are part and parcel of all public health work. Like
Bill Foege, the namesake of the chair he holds, he values leveraging
public resources to gain the most public good. He is now lending
his experience and expertise to the U.S. government. This past year,
his ASM committee received funding from the President’s Emergency
Plan for AIDS Relief, a five-year, $15 billion initiative to combat
the HIV/AIDS pandemic worldwide. The program aims to provide antiretroviral
drugs for 2 million HIV-infected people, prevent 7 million new infections,
care for 10 million people, including orphans, affected by the disease,
and build health care capacity in Africa and the Caribbean.
Klugman is well qualified to advise
the government on how to accomplish such sweeping goals. Indeed,
he knows how to move on the ground, adapt to changing times and
conditions, and make a lot out of a little. These skills, honed
in the turbulent dust of South Africa, now reach out to the world
from a corner office in the Hubert Department of Global Health.
Although this thoroughly modern scientist has found a home in the
richest country in the world, he remains, at heart, a true son of
Africa. |
|
|
|
|
|
Valerie
Gregg is a freelance writer in Atlanta and former editor of this
magazine. |
|
|
|
|
|
|
|
|
|
|
|