infectious disease

Superfast TB test slashes waiting time

writing

(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.

Continue reading →

New insights into an old foe: TB

writing

(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.

Continue reading →

Fighting drug-resistant TB in New York City

writing

(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.

Continue reading →

Hope grows for new TB test

writing

(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.

Continue reading →

New vaccine blocks bird flu

writing

(This article was #12 in Discover Magazine’s top 100 stories of 2007.)

Although avian flu made few headlines in 2007, the virus continued to claim lives in Asia, particularly in Indonesia. The good news is that this year the FDA approved the first bird flu vaccine and announced plans to stockpile it for emergency use during a crisis.

The H5N1 strain of bird flu first appeared in Hong Kong in 1997 and since then has infected more than 330 people, killing more than 200. In 2007, the virus—which normally infects birds and occasionally jumps from birds to humans—affected seven countries, prompting experts to warn that it could gain the ability to jump from person to person and trigger a pandemic.

In April, the FDA approved a two-shot vaccine made by Sanofi Pasteur. In a clinical trial, this vaccine protected 45 percent of the adults who received the highest dose against infection from H5N1. The government said its goal was to stockpile enough doses of the Sanofi vaccine to protect 20 million people as a stopgap measure until a more potent vaccine is available.

Continue reading →

Don’t rush your vaccines

writing

(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.

Continue reading →

Science on trial

writing

(This post appeared on Nature Medicine’s Spoonful of Medicine blog on May 1, 2007.)

It’s always frightening when matters of science are settled in a court of law. And a relief

Robert Gallo

when reason prevails.

Last week, an Australian judge declared that yes, HIV does exist and that it causes AIDS.

The criminal case was filed against a HIV-positive man, Andre Chad Parenzee, for knowingly exposing his sexual partners to the virus. In his defense, he maintained that “the existence of HIV has not been proven” and that “there is no scientific evidence that AIDS is caused by a unique infectious agent.”

The case dragged on for months and although it wasn’t covered much outside the US, did create waves in Australia. Robert Gallo, who established the link between HIV and AIDS in 1984, appeared (by videolink) for the prosecution and was grilled by the defense about his research and his notorious squabble with French virologist Luc Montagnier. AIDS denialism has its supporters even among scientists and the dissident Perth Group, led by two Australian doctors, appeared as “expert witnesses” for the defense.

Parenzee had been convicted on three counts of endangering lives and had appealed. Justice John Sulan said last week that the Perth Group witnesses lacked credibility and threw out the appeal.

The two doctors continue to be employed by the Royal Perth Hospital, although AIDS Truth, a loosely banded group of scientists and activists, and other are calling for their dismissal. As I’ve written here before, AIDS denialism has serious consequences in some parts of the world and is not simply an academic debate. It’s time Australian scientists joined these activists in making sure science prevails.

DDT is back

writing
(This article was #29 in Discover Magazine’s top 100 stories of 2006.)

More than 30 years after the use of DDT was abandoned in many countries, the much-maligned pesticide is making a comeback. In September the World Health Organization openly endorsed indoor spraying of DDT, saying it is not only the best weapon against malaria, it is also cheaper and more effective than other insecticides. The announcement followed a similar move in May by the United States Agency for International Development (USAID).

One of the reasons for the more aggressive stance is President Bush’s Malaria Initiative, launched in 2005 after Congress reproved USAID for spending the lion’s share of its budget on operational costs—and less than 8 percent on the insecticides, bed nets, and medicines that would actually save lives. In 2007, USAID plans to spend more than $20 million on indoor spraying—up from less than $1 million spent in 2005.

Many environmental groups support the use of DDT for malaria—but only in the short term. Meanwhile, USAID representatives say that, when used properly, the chemical poses little risk to the environment or to human health. “Until we find that it is hazardous,” says Admiral Tim Ziemer, coordinator of the President’s Malaria Initiative, “it’s unconscionable not to use something that can save lives.”

FDA approves vaccine for cervical cancer

writing

(This article was #27 in Discover Magazine’s top 100 stories of 2006.)

The cervical cancer vaccine—the second vaccine after the hepatitis B vaccine to target a sexually transmitted disease—debuted this year. In June the Food and Drug Administration approved the vaccine, distributed under the brand name Gardasil, for girls and women ages 9 to 26. The European Union and Australia have also approved the vaccine, and a similar product to be manufactured by GlaxoSmithKline is in the works.

The vaccines work by inducing antibodies to the human papillomavirus, or HPV, which can cause genital warts and cervical cancer. In large clinical trials, the vaccines were more than 99 percent effective in preventing HPV infection. Like most vaccines, however, they are most effective among people who have not yet been exposed to the virus. An American government advisory panel therefore recommended that Gardasil be given routinely to 11- and 12-year-old girls—and in some cases to girls as young as 9.

Every year cervical cancer kills more than 230,000 women worldwide, about 80 percent of them in developing countries. In the United States, the disease claims the lives of roughly 4,000 women each year. Based on a mathematical model, GlaxoSmithKline claims that immunizing every 12-year-old girl with the vaccine would reduce U.S. cases and deaths from cervical cancer by 70 percent. But some conservative groups have opposed the vaccine, saying it might promote sexual activity.

Poor countries also face a more practical obstacle. The full course of the vaccine—three shots over a six-month period—costs about $360. “The biggest issue will be price,” says John Schiller, a senior investigator at the National Cancer Institute, who did some of the early work that led to the vaccine’s development. “It’s the most expensive vaccine we have.”

Polio’s return traced to lapses in India

writing

(This article was #60 in Discover Magazine’s top 100 stories of 2006.)

In May a 39-year-old man in Namibia tested positive for poliovirus, marking the country’s first case in 10 years. Since then, the outbreak there has reached 20 confirmed cases.

This year 10 other formerly polio-free countries are once again battling the disease. Genetic sequencing has traced cases in five of the countries, including Namibia, to a polio strain in India, where the virus remains endemic. As of October 2006, a total of 358 cases have occurred in the poor, densely populated north Indian state of Uttar Pradesh alone, up from 29 in 2005.

The World Health Organization has taken India to task, saying its outbreak is endangering efforts worldwide to keep the disease at bay. To protect a high-risk community from polio, at least 95 percent of the children must be vaccinated; but in late 2005 and early 2006 the vaccination rates in Uttar Pradesh dipped to between 85 and 90 percent.

The Indian government, vowing to eliminate polio by 2007, has discussed a pilot project using an injectable vaccine in addition to oral drops. The injectable vaccine is thought to offer better protection against polio infection in children with diarrhea, which is common in the area.