drug resistance

Nature Outlook: Leukaemia

editing

The leukaemia Outlook is out!

I spent much of April and May working on this special magazine supplement on leukemia for Nature. I came up with the article list, commissioned and edited the articles, worked with the art department on the photos, graphics and cover, and oversaw the production. And I wrote the editorial introducing the contents (below.) You can see the supplement on Nature’s website here.

leukemia

Of all of the cancers that can wage war on the body, leukaemia — the general term for cancers of the blood — has a reputation for being among the least malevolent.

Most solid cancers are riddled with dozens of mutations, making it impossible to know which mutation set a cell on the wrong path, or which one to target. Leukaemia seems simpler: one type of the disease, chronic myeloid leukaemia (CML), can be traced to a single gene fusion (page S4). Scientists were able to develop a drug, imatinib, that exploits the errant gene, increasing the five-year survival for CML to more than 95%. Most children with acute lymphoblastic leukaemia (ALL) also survive

As we show in this Outlook, however, these headline statistics belie the reality for many patients.

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 →

Worst case: HIV + TB

writing

(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.

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 →

Held to ransom

writing

(This Opinion column ran on Nature’s news site on March 26, 2007. You can download a pdf of the original post.)

A pharma giant’s decision to withhold new drugs from Thailand will only hurt patients, says Apoorva Mandavilli.

Is there ever a good enough reason to deny life-saving medicines to an entire country’s citizens? I say no. But it seems pharmaceutical giant Abbott begs to differ.

The Chicago-based company decided on 14 March not to introduce in Thailand any of its seven new drugs — including an antibiotic, an important AIDS drug called Kaletra and medicines to treat blood clots, kidney disease and high blood pressure. Without this crucial registration, the drugs cannot be imported to or sold in that country.

It seems to me that Abbott is, in effect, holding millions of Thais’ lives hostage to force their government to respect its patents. This is good business?

The price of drugs varies from place to place.

The price of drugs varies from place to place.

What’s shocking to me is that the company is making no bones about the fact that its decision is retaliation against Thailand’s decision in January to issue ‘compulsary licenses’ allowing some locals to import or make cheap copies of Abbott’s new version of Kaletra. “This matter is about intellectual property and the integrity of the patent system,” Abbott spokeswoman Melissa Brotz said in a statement.

Lofty words, but I’m reminded more of a schoolyard fight.

Continue reading →

Finally: hints of HIV turnaround in South Africa

writing

(This Opinion column ran on Nature’s news site on November 3, 2006. You can see the original post here.)

It’s about time that this country hard-hit by AIDS promised help for the afflicted, says Apoorva Mandavilli.

aids-in-southafrica-grafitiHIV causes AIDS. That’s not news to you or me, but shockingly it has taken years for the government in South Africa — where about 1,000 people die of AIDS every day — to acknowledge that fact and pledge to provide medicines.

In the past few weeks, the country’s deputy president Phumzile Mlambo-Ngcuka has publicly promised to expand access to AIDS tests, antiretroviral drugs and prevention programmes to those who most need them.

That sounds sensible — if a rather obvious thing for a politician to say — but it’s a far cry from what South Africans had heard until recently.

Health minister Manto Tshabalala-Msimang has extolled the virtues of beetroot, lemon juice and garlic in fighting AIDS. At the international AIDS conference in Toronto this August, her booth prominently featured those items. Six years earlier, at the same conference in Durban, President Thabo Mbeki said he didn’t know anyone with AIDS and questioned its link to HIV.

It’s about time the government changed its tune. As the richest country in Africa, South Africa is in a much better position to combat AIDS than its poorer neighbours. But thanks to the government’s appalling neglect, it hasn’t seen any decline in the rate of new infections.

Continue reading →

The coming epidemic

writing

(Reporting on this article was one of the most emotional experiences of my career. I met many, many sex workers, drug addicts, activists, truck drivers and housewives who had never heard the word AIDS before they were told they were dying from it. As someone born and raised in India, I found the many individual stories heartbreaking, and the denial of the officials deeply sad and scary. This article appeared in Nature in July 2005 as part of a special package on Indian science called Nature Outlook: India. A couple of years after the article appeared, the Indian government revised its numbers drastically downward. I’m deeply skeptical of its estimates, but haven’t yet been able to dig into the truth. You can download a pdf of this article.)

A staggering 5.1 million people are estimated to be HIV positive in India. Apoorva Mandavilli finds a country on the brink of a crisis.

Our son was born in June 1998. He was healthy but after eight months, he had diarrhoea and fever all the time. He was in the hospital many times. The sixth time, they diagnosed him with AIDS. That was when we found out that my wife and I have HIV. Our son died 12 July 2002. I also started to get sick. I didn’t take my medicines regularly; they didn’t tell me not to do that. Now my health has become worse. I haven’t worked in six months.We’ll be paupers. I don’t know what we’re going to do.

— Suresh, air-conditioning technician

Suresh is sitting in a small, dark room at an AIDS clinic in the southern Indian city of Chennai. This city is where the first cases of HIV in India were discovered in 1986 after a police sweep of sex workers. Nearly 20 years later, there are an estimated 5.1 million cases in India, a number second only to that in South Africa. The difference is that in India the epidemic has not yet peaked. According to the CIA, the number of cases in India could top 20 million by 2010.

Continue reading →

Seeking care

writing

(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.”