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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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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The sunshine cure

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I wrote this feature for Nature Medicine after receiving a poorly-written email extolling vitamin D’s benefits. The writer was so impassioned, though, that I was intrigued. This ran in the April 2007 issue. You can view a pdf version of the article here.

Could ten minutes of sunlight a day be all that’s needed to fight multiple sclerosis, cancer and tuberculosis? Apoorva Mandavilli discovers the growing interest in vitamin D’s many virtues.

Long before antibiotics turned tuberculosis (TB) into a curable disease, a Danish scientist found an unusual way to treat it. In 1895 Niels Ryberg Finsen, then just 35, discovered that light from an electric arc lamp cured most people with TB of the skin. Over the following six years, he successfully treated 804 patients.

Nobody understood how the treatment worked, and the condition, lupus vulgaris, was relatively rare. But TB was such a fearsome scourge at the time that Finsen’s discovery won him the 1903 Nobel Prize in Physiology or Medicine. It also began the trend of sending those sick with TB to recover in sanatoriums housed in sunny locales.

It’s only now, more than a century later, that scientists are beginning to understand why Finsen’s method worked.

“It had to be through vitamin D,” says Barry Bloom, dean of the Harvard School of Public Health.

Last year, Bloom and his colleagues published evidence suggesting that vitamin D, made in response to sunlight, stimulates the production of a compound in the body called cathelicidin, which can kill various viruses and bacteria, including the TB microbe (Science 311, 1770– 1773; 2006).

It’s not often that you hear scientists of Bloom’s caliber extolling the virtues of a vitamin; that’s more commonly associated with over-anxious parents or ardent fans of alternative medicine.

Vitamin D may be best known for its role in harnessing calcium from the diet to build strong bones. But Bloom’s report is one of several in the past few years published in top journals— including the New England Journal of Medicine, Journal of the American Medical Association and Nature Immunology—that suggest a far meatier role for the vitamin in the body’s defense against diseases such as tuberculosis, multiple sclerosis (MS) and cancer.

“I think there’s an emerging mainstream acceptance of vitamin D as an immune- regulating factor,” says Eugene Butcher, professor of pathology at Stanford University. “The only people who are going to be skeptical of it are people who haven’t bothered to read the literature in the last five years.”

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Seeking care

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(This is a sidebar to The coming epidemic, an article about the AIDS epidemic in India, and part of a special package on Indian science called Nature Outlook: India.)

When you’re trying to manage an AIDS epidemic and you have limited resources, preventing infection is the logical priority. But where does that leave those who are already infected?

Treating people with AIDS is not easy. At the very least, it requires trained medical staff and the resources to make sure patients take the drugs on time. Nobody knows that better than the doctors at Tambaram Hospital.

Built in 1928 as a sanatorium for patients with tuberculosis, the government centre is 45 km outside Chennai and has more AIDS patients than any other Indian hospital. There are often more than 900 inpatients for its 776 beds, so some have to sleep on the floor. Every hallway is flooded with patients who look skeletal, with shrunken limbs and sallow skin. Outside the wards, hairy black pigs roam beneath drying laundry, accompanied by the rancid smell of sewage.

The hospital was one of eight government centres that together were meant to roll out antiretroviral drugs (ARVs) to 100,000 people over five years. In the first year, which began April 2004, it treated fewer than 1,000.

“From the outside, you may think it is a low number, but for people working here, there are a lot of problems,” says S. Rajasekar, the hospital’s deputy superintendent. Despite repeated requests, he says, the centre has the same resources it did in 1993, when it had just two HIV-positive patients. In 2004, it saw 14,991 new patients and had 140,000 hospital visits from HIV-positive patients. “With just 25 doctors,” says Rajasekar. “Amazing, right?”

By June 2005, government centres, including Tambaram Hospital, had doled out ARVs to 8,000 people. In the same time, since April 2004, small private and non-profit clinics reached an estimated 30,000 sufferers. But these clinics are in a constant struggle for survival.

One such centre is the Naz Foundation’s orphanage in New Delhi. Of the 24 children there — ranging in age from 19 months to 17 years — 10 are on ARVs. Despite one child dying two years ago, only the oldest one knows that she is HIV positive. To spare the children from stigma, their status has also been kept secret from their teachers and neighbours.

One child’s monthly supply of ARVs can cost about Rs900 (US$20). The home was funded by the Gere Foundation until March 2005, but since then money has come almost entirely from small, private donations. “Care is something no traditional donor wants to fund,” says the centre’s director, Anjali Gopalan. “They see it as a black hole, as one donor told me. There’s no return on the dollar.”

Scrambling to treat their patients, doctors at some clinics use medicines that are past their expiry date; others bring free drugs they are given in the United States or elsewhere. Staff at the YRG Care Clinic in Chennai last year began asking people to donate just $10 each. “It’s always beg, borrow, steal, donations, fundraise. That’s how we get funds for care,” says Suniti Solomon, who runs the YRG. “We cannot save the millions out there. The government has to do that.”