It started with a cough, an autumn hack that refused to go away. Then came the fevers. They bathed and chilled the skinny frame of Oswaldo Juarez, a 19-year-old Peruvian visiting the United States to study English. His lungs clattered, his chest tightened and he ached with every gasp. During a wheezing fit at 4 a.m., Juarez felt a warm knot rise from his throat. He ran to the bathroom sink and spewed a mouthful of blood.

Doctors say Juarez''s incessant hack was a sign of what they have both dreaded and expected for years — this country''s first case of a contagious, aggressive, especially drug-resistant form of tuberculosis. Juarez''s strain — so-called extremely drug-resistant (XXDR) TB — has never before been seen in the U.S. XXDR tuberculosis is so rare that only a handful of other people in the world are thought to have had it. Forty years ago, the world thought it had conquered TB and any number of other diseases through the new wonder drugs: antibiotics.

Today, all the leading killer infectious diseases on the planet — TB, malaria and HIV among them — are mutating at an alarming rate, hitchhiking their way in and out of countries. The reason: overuse and misuse of the very drugs that were supposed to save us. Just as the drugs were a manmade solution to dangerous illness, the problem with them is also manmade. It is fueled worldwide by everything from counterfeit drugmakers to the unintended consequences of giving drugs to the poor without properly monitoring their treatment. For example:

-          In Cambodia, scientists have confirmed the emergence of a new drug-resistant form of malaria, threatening the only treatment left to fight a disease that already kills 1 million people a year.

-          In Africa, new and harder to treat strains of HIV are being detected in about 5 percent of new patients. HIV drug resistance rates have shot up to as high as 30 percent worldwide.

-          In the U.S., drug-resistant infections killed more than 65,000 people last year — more than prostate and breast cancer combined. More than 19,000 people died from a staph infection alone that has been eliminated in Norway, where antibiotics are stringently limited.

This April, the World Health Organization sounded alarms by holding its first drug-resistant TB conference in Beijing. The message was clear — the disease has already spread to all continents and is increasing rapidly. Even worse, WHO estimates only 1 percent of resistant patients received appropriate treatment last year. TB germs can float in the air for hours, especially in tight places with little sunlight or fresh air. Tuberculosis is the top single infectious killer of adults worldwide, and it lies dormant in one in three people, according to WHO. Of those, 10 percent will develop active TB, and about 2 million people a year will die from it.

Simple TB is simple to treat — as cheap as a $10 course of medication for six to nine months but if treatment is stopped short, the bacteria fight back and mutate into a tougher strain. It can cost $100,000 a year or more to cure drug-resistant TB, which is described as multi-drug-resistant (MDR), extensively drug-resistant (XDR) and XXDR. There are now about 500,000 cases of MDR tuberculosis a year worldwide. XDR tuberculosis killed 52 of the first 53 people diagnosed with it in South Africa three years ago.

In December 2007 Juarez was sent to A.G. Holley State Hospital. Holley is the nation''s last-standing TB sanitarium, a quarantine hospital that is now managing new and virulent forms of the disease.

Tuberculosis has been detected in the spine of a 4,400-year-old Egyptian mummy. In the 1600s, it was known as the great white plague because it turned patients pale. In later centuries, as it ate through bodies, they called it "consumption." By 1850, an estimated 25 percent of Europeans and Americans were dying of tuberculosis, often in isolated sanatoriums like Holley where they were sent for rest and nutrition.

Then in 1944 a critically ill TB patient was given a new miracle antibiotic and immediately recovered. New drugs quickly followed. They worked so well that by the 1970s in the U.S., it was assumed the disease was a problem of the past. Once public health officials decided TB was gone, the disease was increasingly missed or misdiagnosed and without public funding, it made a comeback among the poor. Then immigration and travel flourished, breaking down invisible walls that had contained TB. Drug resistance emerged worldwide. Doctors treated TB with the wrong drug combinations. Clinics ran out of drug stocks and patients cut their treatment short when they felt better, or even shared pills with other family members.

There are two ways to get drug-resistant TB. Most cases develop from taking medication inappropriately but it can also be transmitted like simple TB, a cough or a sneeze. In the 1980s, HIV and AIDS brought an even bigger resurgence of TB cases. TB remains the biggest killer of HIV patients today.

For decades, drug makers failed to develop new medicines for TB because the profits weren''t there. With the emergence of resistant TB, several private drug companies have started developing new treatments, but getting an entire regimen on the market could take 24 years. In the meantime, WHO estimates each victim will infect an average of 10 to 15 others annually before they die. A.G. Holley was back in business. Only 50 beds are funded today, but those are mostly full. More than half the patients are court-ordered into treatment after refusing to take their meds on the outside. Juarez came voluntarily.

Early on, Juarez''s treatment was similar to chemotherapy. Drugs were pumped into his bloodstream intravenously three times a day, and he choked down another 30 pills, including some that turned his skin a dark shade of brown. He swallowed them with spoonfuls of applesauce, yogurt, sherbet and chocolate pudding, but once they hit his stomach, waves of nausea sometimes sent him heaving. He would then have to force them all down again. After 17 years of handling complex cases — including TB in the brain and spine — the hospital had never seen a case so resistant. It was believed that they would have to remove part of Juarez''s lung.

About 60 million people visit the U.S. every year, and most are not screened for TB before arrival. The results are startling among those tested, said Dr. Angel Contreras, who screens Dominicans seeking to enter the U.S. on immigrant visas. The high rate of MDR-TB in the Dominican Republic coupled with high HIV rates in neighboring Haiti are a health crisis in the making.

Peru is also a hotspot for multidrug-resistant TB. DNA fingerprinting linked his disease to similar strains found there and in China, but none with the same level of resistance. Doctors grappling with these new strains inadvertently give the wrong medicines, and so the TB mutates to become more aggressive and resistant.

Poor countries also do not have the resources to determine whether a patient''s TB is drug-resistant. That requires sputum culturing and drug-susceptibility testing — timely, expensive processes that must be performed in capable labs. WHO is working to make these methods more available in high-risk countries as well as negotiating cheaper prices for second-line drugs. Experts argue if wealthy countries do not help the worst-hit places develop comprehensive TB programs, it puts everyone at risk.

Juarez spent a year and a half living alone in a room. There were days when he simply shut down and refused his meds until his family convinced him to keep fighting. His treatment cost Florida taxpayers an estimated $500,000, a price tag medical director Ashkin says seems like an astronomical amount to spend on someone who''s not an American citizen but he questions how the world can afford not to treat Juarez and others sick with similar lethal strains.

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