public health

Superfast TB test slashes waiting time

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(This article appeared on Nature’s news site on 1 September 2010).

Infection with tuberculosis can be diagnosed easily and accurately in less than two hours.

The new test not only identifies TB in 98% of cases, but also detects resistance to rifampicin, a first-line TB drug.

A new test can accurately diagnose tuberculosis (TB) in people in 90 minutes, compared with the six weeks needed for the current standard test.

The Xpert MTB/RIF test, described today in the New England Journal of Medicine1, identifies TB in 98% of active cases — an improvement of more than 45% on one of the most commonly used current techniques. It also detects whether the TB-causing bacteria are resistant to rifampicin, a first-line drug for TB, in nearly 98% of cases.

“It has the potential to be revolutionary,” says Richard Chaisson, director of the Johns Hopkins Center for Tuberculosis Research in Baltimore, Maryland, who was not involved with the work.

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Cholesterol drugs are prescribed for high-risk kids

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(This article was #38 in Discover Magazine’s top 100 stories of 2008.)

In July, in an update of a 1998 policy statement, the American Academy of Pediatrics (AAP) recommended dropping the age at which at-risk children should be given statins—a class of cholesterol-lowering medication—from 10 years old to 8 years. The drugs would be prescribed to children with an LDL (the “bad” cholesterol) above 190 milligrams per deciliter, or above 160 with a family history of heart disease.

“The idea is to address risk factors as early as possible because we know plaques start to accumulate during infancy,” says Nicolas Stettler, an assistant professor of pediatrics and epidemiology at the Children’s Hospital of Philadelphia and a member of the AAP’s nutrition committee.

Critics say the drugs are a risky fix to broader lifestyle problems. Darshak Sanghavi, chief of pediatric cardiology at the University of Massachusetts Medical School in Worcester, notes that although the FDA has approved some statins for use in children with a genetic problem leading to high cholesterol, there are no studies on the drugs’ long-term side effects in children.

Sanghavi and others also took issue with the AAP’s recommendation of cholesterol screening starting at age 2 for children who are overweight or have other risk factors for heart disease. In this country, that could apply to as many as 10 million children every three to five years. “The screening costs alone will be hundreds of millions of dollars,” Sang­havi says.

New insights into an old foe: TB

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(This article is part of a series of articles on tuberculosis that I wrote for the Summer 2008 issue of NYU Physician.)

WHITE PLAGUE. KING’S EVIL. WASTING disease. Phthisis. Consumption. Tuberculosis (TB) is an old disease with many names and guises. But it wasn’t until last year that scientists discovered how old this ancient scourge really is. Egyptian mummies, skeletal remains, and genetic analysis had all suggested that TB had been around for at least a few thousand years. But in a block of rock mined from a quarry in Western Turkey, anthropologists discovered the fossil of a young male dating back some 500,000 years and infected, unexpectedly, with tuberculosis. They announced in December 2007 that the young man had lesions on the inside of his skull, the imprint of brain membranes that the disease has been ravaging humans for much longer than anyone had ever suspected.

An estimated 2 billion people — nearly one-third of the world’s population — are thought to harbor Mycobacterium tuberculosis (M. tb), the bacterium that causes TB. It grows slowly, lurking in the lungs for years, and outwits the body’s immune system, in part by waiting for the host’s defenses to weaken. In most people, that opportunity never arises, and they show no symptoms of the disease. But once M. tb takes hold, it literally consumes the body from within, eating through lung tissues and the blood vessels that run through it. Every time someone with a full-blown infection speaks, sings, coughs, or sneezes, the bacteria expelled linger in the air for hours, ready to invade the next victim.

This is why TB has so often been a disease of the poor, because it is at its most deadly in overcrowded, unsanitary conditions. In 2006, TB infected 9.2 million people worldwide, claiming the lives of 1.5 million people, most in the developing world. In some parts of South Africa, as many as 70 percent of those with TB are also infected with HIV, because TB is opportunistic.

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Worst case: HIV + TB

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(This article is part of a series of articles on tuberculosis that I wrote for the Summer 2008 issue of NYU Physician.)

When HIV joins forces with TB, the results can be horrific. The neck bulges with lumps as big as an orange, filled with pus-like fluid teeming with the germs that cause TB. Occasionally, these bacteria travel through the blood and lymph vessels, forming lesions in the liver, spleen, and beyond. In chest X-rays, it looks as if the lung were studded with small nodules the size of millet seeds.

This gruesome scenario is rarely seen when TB is the sole affliction. But as HIV ravages the immune system, TB quickly and effortlessly spreads through the body. HIV’s compounding effect on TB has long been known, but recently scientists have discovered that this pernicious partnership works both ways. TB, in turn, eases the path of HIV, dismantling the system that keeps the virus under control in the lungs, allowing it to mutate and multiply.

“If you have HIV and TB, then TB 
will kill you much more rapidly,” notes Michael Weiden, M.D., associate professor of medicine and environmental medicine. In fact, TB is the leading cause of death among people who are HIV-positive, accounting for one-third of AIDS deaths worldwide.

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Fighting drug-resistant TB in New York City

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(This article is part of a series of articles on tuberculosis that I wrote for the Summer 2008 issue of NYU Physician.)

For a few weeks last summer, Americans were riveted by news that Andrew Speaker, then a 31-year-old Atlanta native, may have been flying on commercial airplanes, exposing hundreds of people to a virtually untreatable type of tuberculosis (TB).

They could be forgiven for having thought of TB as strictly a third-world disease. In 2006, 13,767 people in the U.S. had TB — the lowest prevalence in the country recorded since 1953 — while elsewhere 1.5 million people died of the disease.

Speaker was diagnosed in early May 2007, but against medical advice he flew to Greece for his wedding later that month. Tracked down in Rome on his honeymoon, he was told he had extensively drug-resistant tuberculosis (XDR-TB) and was asked to stay put.

Instead he and his wife, Sarah, flew to Prague and Montreal and then drove to New York City. On May 24, officials from the Centers for Disease Control and Prevention directed Speaker to report to Bellevue Hospital, where he was served with a federal warrant that isolated him for medical evaluation, the first such order issued in 44 years.

Bellevue is no stranger to TB. The hospital’s Chest Service, established in 1903 to treat the disease, has contributed a great deal of knowledge about its pathophysiology, clinical behavior, and treatment. In the late 1980s and early 1990s, Bellevue endured a long bout with this familiar foe, grappling with nearly 4,000 cases in New York City, many of them homeless people addicted to drugs and infected with HIV.

“I came here and I found everything was all TB and AIDS,” recalls William Rom, M.D., M.P.H., director of the Chest Service.

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Hope grows for new TB test

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(This article is part of a series of articles on tuberculosis that I wrote for the Summer 2008 issue of NYU Physician.)

To confirm that you have TB, the doctor will ask you to cough up at least a teaspoonful of phlegm, or sputum. You’ll have to come back to the hospital twice more to provide samples, and technicians will painstakingly culture the slow-growing bacteria from the sputum.
 A few weeks after that third visit — by which point you may have exposed others — the doctor should be able to tell you whether you have TB.

This crude sputum diagnostic test is 100 years old. “The situation is fairly horrendous,” says Dr. Suman Laal, Ph.D., associate professor of pathology and mircrobiology.

There are a
few expensive alternatives: fluorescent microscopy, automated culture systems, and tests for the bacterial DNA. But 90 percent of the disease is concentrated in the poorest parts of the world, where these options are not feasible.

Clinically, TB symptoms can be difficult to distinguish from those of
 other bacterial or fungal infections, pneumonia, or certain tumors. Diagnosis with X-rays is subjective and all but useless 
in people who are HIV-positive, and
 a commonly used skin test gives false positives in anyone who has been immunized with the BCG vaccine or 
has been infected with the TB bug’s bacterial cousins.

The ideal test for TB would be fast, cheap, and would deliver a simple Yes or No answer — much like a dipstick pregnancy test. But developing a test like that has proved challenging.

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Controversy over cervical cancer vaccine

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(This article was #26 in Discover Magazine’s top 100 stories of 2007.)

This past year, several countries and at least 24 states in the United States introduced laws to mandate vaccination against cervical cancer for preteen girls. Although the vaccine was initially hailed as a breakthrough, urgent proposals to make it mandatory quickly triggered a backlash. “In the long term,” says Susan Wood, a former director of the FDA Office of Women’s Health, “the rush to get this mandated immediately has done more harm to the issue.”

The FDA approved Merck’s Gardasil vaccine in 2006, after clinical trials showed that it protects against four strains of human papillomavirus (HPV), which together cause about 70 percent of cervical cancers and 90 percent of genital warts. HPV is the most common sexually transmitted virus among Americans (and cervical cancer is the second most common cancer in women worldwide). Because the vaccine doesn’t reverse existing exposure, the CDC recommends it be administered before the age of sexual activity—specifically to girls ages 11 to 12. As for women who already have HPV, two separate studies published in May in the New England Journal of Medicine reported that the vaccine’s effectiveness in preventing cervical lesions dropped to 20 percent or less.

Some conservative groups oppose targeting preteens, arguing that because the virus is sexually transmitted, the vaccine will encourage promiscuity. Meanwhile, bioethicists who are skeptical about compulsory vaccination laws note that all other mandated vaccines protect against diseases easily transmitted in schools. “In my opinion, there’s not a compelling ethical reason [to mandate],” says Richard Zimmerman, professor of family medicine at the University of Pittsburgh. “The ethics is the opposite: to strongly recommend, but not to mandate.”

Male circumcision: A new defense against HIV

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(This article was #15 in Discover Magazine’s top 100 stories of 2007.)

Male circumcision cuts the risk of HIV transmission in men by about 60 percent and should be scaled up in countries hardest hit by the epidemic, the World Health Organization (WHO) announced in March, citing compelling evidence from three large trials in Kenya, Uganda, and South Africa.

Since the 1980s, dozens of smaller studies have suggested that countries with high rates of circumcision, like the Muslim nations of western Africa, have lower rates of AIDS, whereas southern* Africa, where circumcision is rare, has been ravaged by the epidemic. There, a 2006 study suggests, circumcision could prevent about 6 million HIV infections and 3 million deaths over 20 years. Still, the WHO held back its recommendation until 2007, citing the need for randomized clinical trials.

“Circumcision was ignored for ages,” says Daniel Halperin, an AIDS researcher at the Harvard School of Public Health, who laid out the case for circumcision in The Lancet as far back as 1999. “What I mainly criticize the WHO for is that, even with dozens and dozens of powerful studies, they refused to even talk about it.”

Circumcision is thought to prevent infection because the underside of the foreskin is rich in immune cells that are particularly vulnerable to HIV. Small tears in the foreskin during intercourse can also allow the virus to slip into the body.

Circumcision could reduce the odds of an infected man’s transmitting the virus to a female partner by 30 percent or more. For all its benefits, though, the WHO cautions that it should not replace standard methods of prevention like the use of condoms.

Unreasonable doubt

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(This Opinion column ran on Nature’s website June 15, 2007. You can see the original post here.)
A ‘vaccine court’ case on autism could have disastrous consequences if people confuse its verdict with scientific consensus.vaccine-mercury

Why are there so many more cases of autism now than there were 30 years ago? It’s a question the best scientific minds have been unable to answer. But I’m afraid a US court now looking at that question may settle it on the basis of emotion rather than science.

The parents of thousands of autistic children think that the routine measles-mumps-rubella (MMR) vaccine and the mercury-based vaccine preservative called thimerosal damaged their healthy children’s brains and made them autistic — and they’re now suing the US government for damages. On Monday, three ‘special masters’ of the US Court of Federal Claims began hearing testimony in the first of nearly 5,000 such cases, some of which have been pending for years.

I sympathize with these parents and can understand their need to find a reason for their children’s suffering. But I trust in science, and I can’t ignore the fact that so many peer-reviewed studies — and every scientific panel entrusted with evaluating those studies — has come to the same conclusion: neither the MMR vaccine nor thimerosal is associated with autism.

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Don’t rush your vaccines

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(This Opinion column ran in Nature’s news site on May 17, 2007. You can read the original post here.)

The ethical debate about a vaccine for a sexually transmitted disease has been premature, says Apoorva Mandavilli; we don’t even know how well it works.

Here’s a good lesson: before you start pushing for a controversial vaccine to be made compulsory, HPV vaccinebest wait for the research — and I mean all the research — to come up with results.

For more than a year, we’ve been hearing that there is a vaccine that is 100% safe and effective in protecting young girls and women from the deadly viruses that cause cervical cancer.

Merck’s Gardasil, a vaccine against human papilloma virus (HPV), has been hailed as perhaps the biggest boon for women since the contraceptive pill. Across the world, including many American states, politicians and activists have proposed laws to make Gardasil mandatory for girls in their early teens or younger. Australia has already started a national programme of free vaccines for young girls.

All that sounds a bit premature — and rightly so. As we find out more about this vaccine, including new studies in last week’s New England Journal of Medicine1,2, it’s clear we simply don’t know enough about it to be giving it to young girls en masse.

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