KARACHI, Pakistan — Usman, who limps on a leg bowed by the polio he caught as a child, made sure that his first three children were protected from the disease, but he turned away vaccinators when his youngest was born.

He was furious that the Central Intelligence Agency, in its hunt for Osama bin Laden, had staged a fake vaccination campaign, and infuriated by American drone strikes, one of which, he said, had struck the son of a man he knew, blowing off his head. He had come to see the war on polio, the longest, most expensive disease eradication effort in history, as a Western plot.

In January, his 2-year-old son, Musharaf, became the first child worldwide to be crippled by polio this year.

“I know now I made a mistake,” said Usman, 32, who, like many in his Pashtun tribe, uses only one name. “But you Americans have caused pain in my community. Americans pay for the polio campaign, and that’s good. But you abused a humanitarian mission for a military purpose.”

Anger like his over American foreign policy has led to a disastrous setback for the global effort against polio. In December, nine vaccinators were shot dead here, and two Taliban commanders banned vaccination in their areas, saying the vaccinations could resume only if drone strikes ended. In January, 10 vaccinators were killed in Nigeria’s Muslim-dominated north.

Since then, there have been isolated killings — of an activist, a police officer and vaccinators — each of which has temporarily halted the campaign.

The war on polio, which costs $1 billion a year and is expected to take at least five more years, hangs in the balance. When it began 25 years ago, 350,000 people a year, mostly children, were paralyzed. Last year, fewer than 250 were, and only three countries — Afghanistan, Nigeria and Pakistan — have never halted its spread at any point.

While some experts fear the killings will devastate the effort here, Pakistan’s government insists that they will not, and has taken steps to ensure that. Vaccinators’ pay was raised to $5 a day in the most dangerous areas, police and army escorts were increased and control rooms were created to speed crisis responses.

But the real urgency to finish the job began earlier, for a very different reason. Two years ago, India, Pakistan’s rival in everything from nuclear weapons to cricket, eliminated polio.

“Nothing wounded our pride as much as that,” said Dr. Zulfiqar A. Bhutta, a vaccine expert at Aga Khan University’s medical school.

Bill Gates, who is the campaign’s largest private donor and calls beating the disease “the big thing I spend the majority of my time on,” said that Pakistan’s desire to not be further humiliated “is our biggest asset.”

After India’s success and hints from the World Health Organization that it might issue travel warnings, Pakistan’s government went on an emergency footing. A cabinet-level “polio cell” was created. Vaccinators’ routine pay doubled to $2.50. More than 1,000 “mobilizers” were hired to visit schools and mosques to counter the ever-swirling rumors that the vaccine contained pork, birth control hormones or H.I.V., the virus that causes AIDS.

Mullahs were courted to endorse vaccination. They issued 24 fatwas, and glossy booklets of their directives were printed for vaccinators to carry.

Perhaps most important, local command was given to deputy commissioners, who have police powers that health officials lack.

Pakistan is closer than ever. Although cases will not peak until after the summer monsoons, there have been only 21 so far this year. A few years ago, 39 substrains of the polio virus circulated; now only two do. About 300,000 children live in areas too dangerous for vaccinators, but almost all the sewage samples from those areas are clear of the virus.

Ultimately, though, success will depend on more than political will and the rivalry with India. In the wake of the recent killings, it will rely most of all on individual acts of courage, like those by prominent imams who pose for pictures as they vaccinate children.

Or by Usman, who appeared with his polio-stricken son, Musharaf, in a fund-raising video asking rich Persian Gulf nations to buy vaccines for poor Muslims elsewhere.

Or by volunteers, like the women of the Bibi family, in Karachi, who formed a vaccination team. Two of them, Madiha, 18, and Fahmida, 46, were gunned down in December. Television news showed female relatives keening over their bodies. Not only are those women still vaccinating, but Madiha’s 15-year-old sister also volunteered for her spot.

“All the children of Pakistan are our children,” said Gulnaz Shirazee, 31, who leads the team. “It’s up to us to eradicate polio. We can’t stop. If we’re too afraid, then who will do it?”

A Moving Target

If there is one spot on earth where polio may make its last stand, it is a cramped slum called Shaheen Muslim Town No. 1 in Peshawar, a hotbed of anti-Western militancy. Since sampling began, its sewers have never tested negative for the virus.

It is a neighborhood of migrant Pashtun families who rent rooms briefly and move on, looking for menial jobs picking fruit or making bricks. On a recent sunny afternoon, its alleys were full of carts drawn by donkeys whose faces were decorated with the red prints of hands dipped in henna. Many women wore the full burqa popular in Afghanistan.

In this part of the world, virtually all those with polio are from the Pashtun tribe, in which resistance to vaccination is highest. It is Afghanistan’s largest ethnic group and the wellspring of the Taliban, but a minority in Pakistan. Pakistani Army sweeps and American drone strikes have driven many Pashtuns from their mountain valleys into crowded cities.

Peshawar worries even Dr. Elias Durry, a normally optimistic polio specialist with the W.H.O. “You can get 90 percent vaccine coverage, and come back a few months later, and it’s 50 percent,” he said. “People just move so quickly.”

Shaheen’s sewers are concrete trenches about a foot deep, into which wastewater, rendered milky white by dish soap, flows from pipes exiting mud-brick houses. A child reaching into one for a stick to play with showed how easily the virus, carried in fecal matter, could spread.

Though the area has clean water from a well, the steel pipe it flows through at times dips inside the sewerage trench. It has dents where trucks have banged it, and it is pierced by connectors, some attached just to rubber hoses.

“Piped water with sewage mixed in is worse than no piped water,” said Dr. Bhutta of Aga Khan. “Sometimes rural populations have it better. They carry water from the river, and they defecate in open fields, so there’s no mixing.”

Pakistani children suffer diarrhea so often that half the country’s young are stunted by it. Polio immunity is low, even in vaccinated children, because other viruses crowd the gut receptors to which the vaccine should attach.

At the clinic in Shaheen, the doctor running the polio drive, an ophthalmologist, complained that he got too little police help.

“I have 28 teams, so I requested 56 constables,” he said. “I was given 12.”

He said the underpaid officers inevitably knocked off at midday because their station house serves a hot meal.

The same problem was echoed in Gadap Town, a Karachi neighborhood where vaccinators were killed in December. As a team worked its way from house to house with a reporter, it had every reason to feel secure: because the visit was arranged by an official, six officers with AK-47s came along.

But another team passing by was guarded only by an aged sergeant with a cudgel.

“Yes, we have a security problem,” Dr. Syed Ali, a local official, said quietly on a side street. “What is a stick in front of a gun?”

The isolation and poverty of the Pashtun tribe underlie its resistance. Many of its imams are from Islam’s fundamentalist Deobandi sect, which emerged in the 19th century as a reaction to the British conquest.

Many Pashtun neighborhoods receive few government services like health clinics, paved streets or garbage pickup, but get shiny new billboards trumpeting the polio fight paid for by Western donors.

“People tell us, ‘We need schools, we need roads, we need housing, and all you bring our children is polio, polio, polio,’ ” said Madiha, a black-veiled Gadap vaccinator.

In the middle of last year, it became known that in 2011, the C.I.A. had paid a local doctor to try to get DNA samples from children inside an Abbottabad compound to prove they were related to Bin Laden.

Even though the doctor, Shakil Afridi, who is now serving a 33-year sentence for treason, was offering a hepatitis vaccine, anger turned against polio drops.

Leaders of the polio eradication effort could not have been more frustrated. They were already fighting new rumors that vaccinators were helping set drone targets because they have practices like marking homes with chalk so that follow-up teams can find them. Now, after years of reassuring nervous families that the teams were not part of a C.I.A. plot, here was proof that one was.

“It was a huge, stupid mistake,” Dr. Bhutta said.

Anger deepened when American lawmakers called Dr. Afridi a hero and threatened to cut off aid if he was not released. The W.H.O. and the Unicef, afraid of offending the United States, did not protest publicly. Unicef’s executive director, Anthony Lake, is a former White House national security adviser, which put the agency in an awkward position, an agency official said on the condition of anonymity because of the sensitivity of the issue.

But the deans of a dozen top American public health universities wrote a letter of protest to the Obama administration. Mr. Gates said he endorsed it, though he was not asked to sign. He also said he discussed the issue with Tom Donilon, the former national security adviser, though he would not give details of the conversation.

Fistfuls of Rupees

New opposition has forced the adoption of new ground tactics.

Dr. Qazi Jan Muhammad, the former deputy commissioner of Karachi East, called his approach “a mix of carrots and sticks.”

Whole apartment buildings were missed, he discovered, because Pashtun watchmen were shooing away vaccinators.

“I had the police tell them: ‘Either you let them in, or you go behind bars,’ ” he said.

He had traffic circles blocked so teams could approach each car, and he led some teams himself holding fistfuls of rupees, worth about a penny each.

“I saw a girl, about 11, carrying her 2-year-old sister,” he said. “I gave her a 10-rupee note and said, ‘Will you allow me to give drops to your sister? You can get sweets for yourself.’ ”

“She told all the children, ‘A man is giving away 10 rupees,’ and they all came rushing. I vaccinated 400 kids for only 4,000 rupees.”

The sewers of his district, which has several million inhabitants, are now virus-free.

At the Front Lines Again

The country’s new determination has also brought Rotary International back to the front lines.

The club, founded in Chicago in 1905, started the global polio eradication drive in 1988. It has had chapters in what is now Pakistan since 1927, and is now led by Aziz Memon, a hard-driving textile magnate.

Mr. Memon, 70, and other Rotary-affiliated executives have used their money and political connections to keep the pressure on. They compensated the killed vaccinators’ relatives and held news conferences at which the families urged others to continue fighting.

Rotarians also work in places that terrify government officials. In an industrial neighborhood in Karachi, where both gangs and the Taliban hold sway after dark, Abdul Waheed Khan oversaw a Rotary polio clinic in his school, Naunehal Academy. A big, gregarious man, he angered the Taliban by admitting girls to his academy and offering a liberal arts education instead of only Koran study. His only security was local teenagers who ride motorcycles beside his car to keep anyone from pulling up alongside.

In March, he hosted Dr. Robert S. Scott, the 79-year-old Canadian chairman of Rotary’s polio committee, who flew in to vaccinate children to prove that the fight would go on despite the December killings.

“I had a fatwa put on my head,” Mr. Khan said in April as he led a tour of the clinic. “They said I was Jewish. I had a friend issue a counter-fatwa saying I was a good Muslim.”

On May 13, Mr. Khan was killed by gunmen who also wounded his 1-year-old daughter.

His clinic will not close. “No one can replace Waheed, but life has to go on,” Mr. Memon said.

‘This Is Good Work’

Rotary also sponsors a tactic used to reach children from areas too dangerous for home visits: “transit point” vaccinating.

At a tollbooth on the highway into Karachi, Ghulam Jilani’s team takes advantage of an army checkpoint. As soldiers stop each bus to search for guns, Rotary vaccinators hop aboard. On a typical day, they reach 800 children.

Yes, Mr. Jilani said, the soldiers’ presence may intimidate some resistant families into complying. Also, he added brightly: “We scare them a little. We say, ‘You are entering a city with the disease. Don’t you want your children safe?’ ”

About 90 percent comply, he said, sometimes after a public argument between a father who believes the rumors and a mother, outside their home and at times backed by other women on the bus, insisting the children be protected.

Near the Afghan frontier, where thousands of children live in valleys under Taliban control, teams do the same at military roadblocks. At hospitals, which are usually guarded by soldiers, nurses will pack extra doses of the vaccine on ice for families willing to smuggle it to neighbors.

Some frontier clan chiefs have lost their government stipends for opposing vaccination, and officials have threatened to deny national identity cards to their clans. But the chiefs are in a bind; the Taliban have assassinated many for cooperating with the government.

Mr. Memon of Rotary opposes what he called “these coercive gimmicks.”

“We can’t twist arms,” he said. “We want to win them over with love and affection.”

Among hundreds of men wearing turbans and topees at Karachi’s main train station, Muhammad Arshad stood out in his blue baseball cap with Rotary’s bright yellow gearwheel.

Threading his way through the crowd squatting on Platform 1, he picked out children under age 5.

“What a nice boy,” he said to Sohail Ameer, chucking his infant, Abadur Rahann, under the chin. “May I give him drops against polio?”

Mr. Ameer agreed, and it was over in seconds. Abadur looked nervous, but he did not howl and squirm like some.

After the December killings, Mr. Arshad worried briefly, he said. “But then I thought: This is good work, and God will protect me.”

Friendly strangers came up to the Rotary table to suggest he play it safe and quit. He replied that the railroad police would protect him.

His wife tried the hardest.

“But I told her,” he said. “If a man has to die, he can die even at home. I’m going back to work.”