PRETORIA,
South Africa – It's 8 a.m. and Dr. Theresa Rossouw is already drowning behind
a cluttered desk of handwritten HIV charts — new, perplexing cases of patients
whose lifesaving drugs have turned against them.News (Updated
January 3, 2010)
[Home]
[Previous
news]
3 January 2010
Scientists seeking to
understand how to make an AIDS vaccine have found the cause of a major
roadblock. It turns out that the immune system can indeed produce cells with the
potential to manufacture powerful HIV-blocking antibodies – but at the same
time, the immune system works equally hard to make sure these cells are
eliminated before they have a chance to mature.
"These studies show that a potentially protective neutralising antibody
against a viral disease is under the control of immunological tolerance,"
said Barton Haynes, MD, director of the Center for HIV/AIDS Vaccine Immunology (CHAVI)
at
Over the years, scientists
have assumed that B cells – one of the first lines of defense against
infection – are simply not able to "see" the HIV virus. HIV has the
ability to hide its most vulnerable parts from immune system surveillance, and
researchers generally assumed that helped explain why B cells often took weeks
and even months to arise following infection.
But several years ago,
Duke researchers hypothesised that the antibodies required to broadly neutralize
HIV may not be produced in the first place because the immune system
"sees" them as a potential threat – due to their similarity to
antibodies that promote autoimmune disease – and destroys them.
To see if this is indeed
what happens, Laurent Verkoczy, PhD, assistant professor of medicine at Duke and
the lead author of the study, and Haynes genetically engineered a mouse that
could only produce B cells containing a rare but potent broadly neutralising
human antibody that is able to block HIV infection.
Researchers found that the
mouse's immune system produced plenty of early stage B cells bearing this human
neutralising antibody on their surface but eliminated most of them before they
had a chance to fully evolve into more mature B cells capable of secreting the
antibody.
"This work may mean
that we need to think and act very differently in envisioning how a successful
vaccine may work," said Verkoczy. "The good news is that while about
85 percent of the "right" kind of B cells are eliminated, about 15
percent survive and wind up in circulating blood, but are turned off. One goal
in vaccine design may be to figure out how to wake them up so they can go to
work."
"We have now unveiled
a major reason why members of this class of neutralising antibodies are not
routinely made: Our own immune systems block their production because they are
perceived as potentially harmful, when in reality, they are not," said
Haynes. "This is a very unusual way the virus has developed to evade the
immune system."
Haynes says researchers
plan on using the new mouse model to test ways to teach the immune system to
enable the production of powerful neutralising antibodies capable of blocking
HIV.
(Source:
By Nora Proops
Jan 2, 2010
One study monitored
mortality rates and causes of death in HIV-infected children from 1993 to 2006,
a period of time when highly active antiretroviral treatment (HAART) was
introduced.
The other study estimated
life expectancy and average years of life lost in adults following HIV
diagnosis.
Researchers found that
pediatric death rates significantly decreased between 1994 and 2000, from 7.2 to
0.8 per 100 person years. Rates remained steady through 2006.
Average adult life
expectancy after HIV diagnosis in 2005 was 22.5 years compared with 10.5 years
in 1996.
Average years of life lost
in adults also improved, from 32.9 years in 1996 to 21.1 years in 2005.
In children, the causes of
death were mainly end-stage AIDS and pneumonia. Deaths due to opportunistic
infections declined from 37 percent to 24 percent.
Previous studies have
found HAART to be associated with improved survival among HIV-infected patients.
In a study published in December, Swiss researchers found decreased suicide
rates in patients after the introduction of HAART (see related AIDS Beacon
news).
Both JAIDS articles report
negative trends as well. The pediatric study shows that mortality rates in
children with HIV/AIDS are still 30 times higher than in children in the general
In adults, life expectancy
for females improved less than in males (women gained 11 years, while men gained
12.1 years). Additionally, minorities live shorter lives than Caucasians. Life
expectancy for African-American males was the shortest, followed by Hispanic
males and then Caucasian males.
These findings emphasize
the importance of addressing quality-of-life issues specifically in female and
minority patients.
The study tracking death
rates among HIV-positive children followed 3,553 subjects participating in the
Pediatric AIDS Clinical Trials Group (PACTG) 219/219C from 1993 to 2006 for a
median of 5.3 years. The majority of children were under three years of age upon
entering PACTG.
The researchers observing
the mortality rate among HIV-positive adults relied on national HIV surveillance
data since 1996 from 25 states.
JOHANNESBURG,
31 December 2009 (IRIN) - A new technology being pioneered in South Africa may
make screening for tuberculosis (TB) faster, cheaper and more reliable – and
it's all based on technology found on a typical trip through airport security.
The new computer
diagnostic system known as TBDx takes digital pictures of sputum samples and
searches them for TB's structural "fingerprint." Some airport scanners
work in much the same way, searching luggage for the structural fingerprints of
plastic explosives, for example.
The system is being
pioneered by health research organisation, the Aurum Institute in partnership
with
A prototype is already in
the works and once fully automated will be able to run independently 24-hours a
day. It has already proven 10 percent more effective at identifying TB bacilli
than conventional TB tests which rely on laboratory technicians to manually load
slides and look for the bacilli under a microscope.
With its combination of
sensitive diagnostic technology and labour-saving automation, TBDx could
revolutionize TB testing in high burden countries like South Africa that have
seen a resurgence of TB in the last decade on the back of the HIV/AIDS epidemic.
About 70 percent of South
Africans diagnosed with TB are co-infected with HIV and, despite being curable,
the disease is the country's leading natural cause of death and one of the main
factors behind
"The diagnosis of TB
is fraught with difficulties," Dr David Clark, Deputy CEO of the Aurum
Institute told IRIN/PlusNews.
He noted that current
methods of TB diagnosis continue to rely on technology developed by Robert Koch,
the German physicist who discovered TB a century ago. "If we were going to
fight a war today with equipment we used 100 years ago, we'd be mad," he
said.
Testing the possibilities
TBDx can be operated by
personnel with no special skills, freeing up a scarce supply of lab technicians
to do other important work. It may also greatly improve working conditions for
lab technicians who currently spend hours hunched over microscopes searching for
tiny TB bacilli.
"Out of 100 slides
that come to you...maybe six percent will be positive," said
The new technology does
not entirely do away with the need for skilled technicians. It can be set to
flag slides that are difficult to diagnose – a function that
South Africa's NHLS is
waiting for the new technology to be costed before making a decision about
whether to adopt it nationally, but TBDx is likely to be more cost effective
than the current labour-intensive method of TB testing which costs about US$3
per slide.
"We will have to do
the operational research and cost-effectiveness studies, but it's very
promising," said Gerrit Coetzee, head of the National TB Reference
Laboratory of the NHLS. He added that TBDx's potential to increase lab
productivity, and improve and standardise diagnosis were among its main draws.
If the NHLS does choose to
adopt the technology, a national rollout is still at least three years away,
according to Coetzee. The system would most likely be piloted in high volume
laboratories before being scaled-down for use at lower levels of the health
system.
By MARGIE MASON and MARTHA
MENDOZA, Associated Press Writers Dec 30, 2009
PRETORIA,
South Africa – It's 8 a.m. and Dr. Theresa Rossouw is already drowning behind
a cluttered desk of handwritten HIV charts — new, perplexing cases of patients
whose lifesaving drugs have turned against them.
Her cell phone chirps. Her
desk phone bleats. She scribbles notes on a planner, spins in her chair, juggles
requests about labs and drug regimens.
Rossouw is on the front
lines of a new battle in the fight against HIV: The drugs that once worked so
well are starting not to work. And now the resistance is showing up in
sub-Saharan
Ten years ago, between 1
percent and 5 percent of HIV patients worldwide had drug resistant strains. Now,
between 5 percent and 30 percent of new patients are already resistant to the
drugs. In Europe, it's 10 percent; in the
In sub-Saharan
The story of HIV mirrors
the rise worldwide of new and more deadly forms of killer infections, such as
tuberculosis and malaria. These diseases have mutated in response to the misuse
of the very drugs that were supposed to save us, The Associated Press found in a
six-month look at soaring drug resistance worldwide.
In Rossouw's shabby little
HIV clinic, the tragedy has arrived. She's increasingly bombarded with
drug-resistant cases, and there's nothing in her arsenal of medicines to throw
at them.
"For the first two or
three years I was not seeing it. It was rare," she said, rifling through a
patient's tattered record. "Now it is really daily. I think in the next
five years, we are going to have such a need."
____
It's midmorning and
Rossouw's first patient slips inside from the crowded hallway where up to 200
others wait on wooden benches. Monica, who only wishes to be identified by her
first name for fear of discrimination, takes a seat.
Rossouw, 37, greets her
warmly in their native Afrikaans. She is the only doctor — out of the six at
Monica, 45, looks and
feels healthy. It's hard to believe she's had HIV for nearly a decade. Now she's
faced with a new threat, one Rossouw isn't sure the patient fully understands.
Monica has widespread drug
resistance — everything has stopped working. But she's not feeling the sting
yet, and it's hard for her to believe a piece of paper that says her meds aren't
working.
In sub-Saharan
The United Nations
estimates $25 billion will be needed to fight AIDS worldwide in 2010, but
probably only half that sum will be available. That estimate doesn't account for
drug-resistant strains, which could cost $44 billion by 2010.
Monica's slip came in
2004, when, distraught over her mother's death, she went off of her treatment
for two months.
"I took the death
badly," she said softly. "I had an appointment with the doctor and
decided that now that my mom has died, I must die as well."
The HIV drugs used in
Rossouw found an obsolete
HIV drug at another hospital and hopes it will keep Monica alive. But she's
experimenting at this point.
Each year more drug
resistant strains are detected. There were 80 different documented strains in
2007; 93 in 2008, according to
_____
By noon Rossouw, who also
teaches, studies and researches at the University of Pretoria, has taken a dozen
phone calls and dispensed advice to nurses, doctors, students and patients
inside and out of the hospital.
Now crisis is hitting: A
patient has been admitted after her HIV drugs began poisoning her system. Her
pancreas is damaged, her life at stake. The HIV regimens used in
Rossouw orders the woman
off the meds. If she survives, Rossouw figures she'll be adding her name to the
black binder atop her desk, a list with names of about 200 patients failing at
least one round of therapy. A few, like Monica, have reached the end of the
line.
"What if they start
spreading that resistance in the community?" Rossouw says, shaking her
head. "I don't think any of us actually sat down and thought about the
consequences of widespread resistance in the population. We don't have enough
money as it is."
There are 8,000 patients
who crowd into the clinic. Of those, 5,000 are taking antiretrovirals. The rest
are forced, under South African guidelines, to wait until their immune systems
weaken more.
Rossouw came to this
battered public hospital in 2005, after realizing she was bored with a
comparatively tranquil private practice. What she saw there leads her to blame
private doctors who mismanage patients for the rising resistance. They prescribe
the wrong meds, she says, and miss failing therapy.
"They just start them
on treatment and hope it's going to solve all of their problems," she says.
Rossouw monitors
everyone's blood in her clinic for changes in the virus so she'll know if their
drugs are losing potency. In smaller private practices or poor neighboring
countries like
A study published earlier
this year found widespread drug resistance in
"Right now, treatment
rollout is in the honeymoon of success and we haven't treated enough people for
long enough to start seeing some of the consequences of what we're doing,"
said Dr. John Mellors, an HIV drug resistance expert at the
_____________
Down a dingy hall and
outside across a concrete walkway is the pediatric unit where some of Rossouw's
most stubborn resistance cases are treated. One 6-year-old girl does not respond
to any drugs, despite taking them properly. It's a mystery case that baffled
some of the world's leading drug resistance experts.
This afternoon it's time
for 4-year-old Mashamaite's appointment. Born HIV free, this toddler's diabetic
mother died when he was 4 months old. His aunt, who had also just given birth,
offered to breastfeed and raise the baby. But she didn't know she was
HIV-positive. She infected Mashamaite and then she died. Before he ended up back
with his dad and stepmother, his treatment was stopped for two to three months,
allowing drug resistance to build.
Now first-line HIV drugs
don't help Mashamaite, so they're trying the second and last option.
Rossouw and her colleagues
say kids are perhaps the hardest to treat because they depend on someone else to
make sure the meds are swallowed. Often, because AIDS has ravaged so many South
African homes, the child bounces among surviving relatives. Sometimes teenage
siblings are tasked with diluting the pills and squirting them into the little
mouths with syringes.
Mothers are another
difficult category. In a country where nearly 30 percent of all child-bearing
women are infected, drugs given during delivery have helped prevent many babies
from being born with HIV. But moms in
In Rossouw's office, the
phone hasn't stopped ringing and the nurses haven't stopped interrupting her. A
signature here, a prescription there. As the afternoon sun begins to sink, the
clinic's hallway has cleared. Rossouw is the last one to leave.
She locks the door and
strides across the campus, up three flights of stairs into the main hospital.
"Hello!" she
calls to Freddy, an aging patient, gaunt and weak.
He tells her he stopped
taking the pill, 'the big one,' that was causing nonstop diarrhea. He took the
others, he says, until they ran out.
"Sometimes I take
them and sometimes not," he says, his voice faint. "If my stomach
isn't running, I'm strong, strong, strong. When I run out of drugs, there's no
money for transport to the clinic."
Rossouw grips his hand
while sitting on his bed.
"I'm worried that we
don't have any options left. You look to me now like you looked without
treatment," she says. "Do you think maybe there might not be any more
treatment?"
"No," he says,
looking away. Understanding. "Those ones that make me sick ... maybe if I
can get others, I'll feel better. I'm always vomiting. I want to try everything
that can help me."
This small rally of hope
is all the doctor needs. She orders tests to determine if there are any drugs
left that might work. She will attempt to resurrect him, choosing from her slim
selection of pills.
It's now evening and
Rossouw heads for dinner, relaxing at a restaurant with her husband and their
7-year-old daughter. But just as the pizzas arrive, the doctor's tireless cell
phone sings again.
She answers. Her voice
cracks. The tears come before she can push her chair back.
For the first time in her
hectic day, she takes a moment alone to grieve for a patient even she couldn't
save.
By MARGIE MASON and MARTHA
MENDOZA, Associated Press Writers Margie Mason And Martha Mendoza, Associated
Press Writers Mon Dec 28, 8:34 am ET
PAILIN,
Just off a muddy
rutted-out road, it is nothing more than a handful of Khmer-style bamboo huts
perched crookedly on stilts, tucked among a tangle of cornfields once littered
with deadly land mines.
Yet this spot on the
Thai-Cambodian border is home to a form of malaria that keeps rendering one
powerful drug after another useless. This time, scientists have confirmed the
first signs of resistance to the only affordable treatment left in the global
medicine cabinet for malaria: Artemisinin.
If this drug stops
working, there's no good replacement to combat a disease that kills 1 million
annually. As a result, earlier this year international medical leaders declared
resistant malaria here a health emergency.
"This is not business
as usual. It's something really special and it needs a real concerted
effort," said Dr. Nick White, a malaria expert at
Malaria is just one of the
leading killer infectious diseases battling back in a new and more deadly form,
the AP found in a six-month look at the soaring rates of drug resistance
worldwide. After decades of the overuse and misuse of antibiotics, diseases like
malaria, tuberculosis and staph have started to mutate. The result: The drugs
are slowly dying.
Already, The Associated
Press found, resistance to malaria has spread faster and wider than previously
documented. Dr. White said virtually every case of malaria he sees in western
Mosquitoes spread this
resistant malaria quickly from shack to shack, village to village — and
eventually, country to country.
And so O'treng, with its
45 poor families, naked kids, skinny dogs and boiling pots of rice, finds itself
at the epicenter of an increasingly desperate worldwide effort to stop a
dangerous new version of an old disease.
_______
Bundled in a threadbare
batik sarong, 51-year-old Chhien Rern, one of O'treng's sick residents, sweats
and shivers as a 103-degree fever rages against the malaria parasites in her
bloodstream.
Three days ago Chhien Rern
started feeling ill while looking for work in a neighboring district. So she did
what most rural Cambodians do: She walked to a little shop and asked for malaria
medicine. With no prescription, she was handed a packet of pills — she's
unsure what they were.
"After I took the
drugs, I felt better for a while," she says. "Then I got sick
again."
The headaches, chills and
fever, classic symptoms of malaria, worsened. Chhien Rern's daughter persuaded
her to take a motorbike taxi past washed out bridges and flooded culverts to the
nearest hospital in Pailin, a dirty border town about 10 miles from O'treng.
Doctors say there's a good
chance Chhien Rern was sold counterfeit drugs.
People generate drug
resistant malaria when they take too little medicine, substandard medicine or
— as is all too often the case around O'treng — counterfeit medicine with a
pinch of the real stuff. Once established, the drug-resistant malaria is spread
by mosquitoes. So one person's counterfeit medicine can eventually spawn
widespread resistant disease.
Yet in most parts of the
world, people routinely buy antimalarials over the counter at local pharmacies
and treat themselves.
A recent study out of
neighboring Laos found 88 percent of stores selling artemisinin-based drugs, the
same ones scientists are desperately trying to preserve, were actually peddling
fakes. Worse, nearly 15 percent of the counterfeits were laced with small hints
of artemisinin, which could prompt resistance. The researchers found indications
that some were made in
The counterfeits, along
with outdated drugs, are jumping continents. In
WHO and Interpol formed a
task force three years ago to try to stop counterfeiters, seizing millions of
fake malaria, tuberculosis, HIV and other pills in Southeast Asia and
"One of the problems
is that there's not really any enforcement, so what happens when they find a
drug that's counterfeit or substandard?" says David Sintasath, a regional
epidemiologist at the nonprofit Malaria Consortium in
Countless unlicensed shops
in
"The drug has been
around for a long time and misused for a long time and this is all encouraging
the parasite to develop resistance," says Dr. Delia Bethell, of the U.S.
Armed Forces Research Institute of Medical Science, whose research has been at
the forefront of identifying emerging resistance on the border.
Back in western
But Nop Chen, a former
Khmer Rouge medic, points to a small Cambodian seal on the boxes and says he
feels confident the drugs are the real deal. Still, he acknowledges he is not
licensed to sell the pills and he's unsure where they originated.
"I'm not concerned
because it's got the sticker and the stamp," he says, squinting at the
Khmer script on the labels. "Because of the logo, I trust it to not be fake
— it was made in
_______
Walk past O'treng's
cluster of sagging huts, cross another cornfield and hike a twisted mile on a
dirt track to a wooden shack where a string of smoke is curling through the
wooden floor planks in a largely futile effort to keep mosquitoes away. It's
here that skinny 13-year-old Hoeun Hong Da wakes up on the floor nauseous and
burning with fever.
Hong Da recovered from
malaria two months ago, but now the dizziness and headaches are back. He's been
sickened by the disease six or seven times in his short life — too many to
remember. He knows that if he doesn't get to a hospital soon, he could die.
With no new treatments in
the pipeline, normally reserved scientists are quick to use words like
"disaster" or "catastrophe" when asked what might happen if
they don't contain the disease that's ravaging young Hong Da before it spreads
to
For the past 50,000 years
the malaria parasite has been evolving, and migrating, alongside humans. It
moves within the huts of O'treng, and into neighboring towns when men like Hong
Da's father and older siblings float from job to job.
Some work is close enough
for them to return home at night, but other jobs keep them away for stretches of
time. They sleep in tight rows, sweating and weary, in disintegrating bamboo
huts with workers who are also traveling, and possibly infected with malaria.
The concept of containing
drug resistance has never been tried before. Scientists wonder: How do you
control the spread of a resistant parasite transmitted by mosquitoes that bite
people who live and work in infested jungle areas, then scatter in all
directions, all the time?
This area, the former
stronghold of the murderous Khmer Rouge, has a notorious history. Burmese
migrant workers who once mined rubies and sapphires in these now deforested
hills are believed to have helped transport strains resistant to the drug
chloroquine back to Myanmar a half century ago. From there it spread to
A decade later, history
repeated itself when resistance to the drug sulfadoxine-pyrimethamine followed
the same path.
Now, in western
But grants haven't stopped
lines of Cambodians, sick or not, from queuing up every morning at
And grants haven't stopped
the parasite from spreading in the O'treng area, despite widespread bednet
distribution, awareness campaigns and enhanced surveillance systems. Some
scientists say the only sure way to fix the problem is to eradicate malaria
entirely from western
"It's really
dangerous," says Dr. Rupam Tripura, who's conducting a study in Pailin for
the Wellcome Trust-Mahidol University-Oxford Tropical Medicine Research Program.
"What will happen to the mosquitoes? Can you kill those living in the
jungle? No, so you cannot kill the strain."
_______
If O'treng is the
epicenter of this emerging disease, Phoun Sokha is the point man aimed at
controlling it.
At 47, Phoun Sokha is the
village malaria worker who lives at the mouth of the hamlet and proudly displays
an orange plastic kit that resembles a tackle box.
Phoun Sokha is serious
about his packets of medicine and his rapid tests to prick blood from sick
villagers' fingers to determine if they have malaria and if so, what type. He
makes sure patients are taking their free medicines and checks to see if they're
improving. If not, Phoun Sokha can even arrange transportation to the hospital.
But treating O'treng's
malaria patients can be frustrating.
"Some of the
patients, when they went to the hospital, after one month, maybe they get
malaria again," he says.
Today Hong Da, the village
boy who has fought malaria so many times before, heads home from the hospital
after a few days of treatment. He clutches a new mosquito net he hopes will
prevent yet another infection. Together, the recovering boy and his weathered
mom shuffle past sick neighbor Chhien Rern's shack before disappearing among the
tassels of the cornfield toward their home.
But all is not well.
Under a tattered quilt,
Hong Da's 9-year-old sister Hoeun Chhay Meth is curled on a thin mattress atop
the wooden floor inside the family's open-air home.
She had malaria alongside
her brother two months ago. They share a mosquito net that she burned a hole in
when she stayed up one night reading by the light of a makeshift candle. Her
brother thinks that's how the mosquitoes infected them.
"Very afraid of
dying," says Chhay Meth, who has started taking medicine provided by the
village malaria worker. "I feel worse than before. I cannot walk myself or
stand up by myself and cannot eat well."
Hong Da understands. He
gently lifts his little sister's limp body, scooping her up, his strength
returning. Chhay Meth reaches weakly for her mother.
Like her big brother, this
child doesn't know about counterfeit drugs or antimalarials.
She only knows she's sick.
And the medicines don't seem to work as well any more in this little village she
calls home.
_______