The attack followed more American casualties over the weekend that pushed the U.S. military's death toll for the 11-year-war above 2,000 - a figure that has climbed steadily in recent months as attacks on the so-called "partnering" initiative have risen.
Joint patrols between NATO and Afghan forces, like the one targeted Monday, have been limited following a tide of attacks by Afghan soldiers and police on their international allies. Last month, the U.S. military issued new orders that require units to get approval from superiors before conducting operations with Afghans. Two weeks later, U.S. officials said most missions were being conducted with Afghans again, though the system of approvals remained in place.
The close contact - coalition forces working side by side with Afghan troops as advisers, mentors and trainers - is a key part of the U.S. strategy for putting the Afghans in the lead as it and other nations prepare to pull out their last combat troops by the end of 2014.
But the rising death toll for international troops has raised troubling questions about whether they will achieve their aim, boosting calls inside the alliance for a pullout as soon as possible and jeopardizing the goal of training the Afghans to fully secure their country.
In the latest attack, the bomber struck the mixed police and military patrol shortly after they got out of their vehicles to walk through a market area in the eastern city of Khost. It was a reminder that the insurgency is still fighting hard after 11 years of a U.S.-led war to defeat the militants.
In addition to three Americans and their translator, six civilians and four police officers were killed in the explosion, provincial government spokesman Baryalai Wakman said. The police officers were part of a specialized quick-reaction force, he added.
Blood could be seen on the market road as Afghan police and soldiers tried to clean up the area after the blast. Slippers and bicycle parts were strewn about.
"I heard the explosion and came right to this area. I saw the dead bodies of policemen and of civilians right here," said policeman Hashmat Khan, who ran to the site of the blast from his job as security for a nearby bank.
Coalition spokesman Maj. Adam Wojack would only confirm that three NATO service members and their translator died in a bombing in the country's east, without giving an exact location or the nationalities of the dead.
The international military alliance usually waits for individual nations to announce details on deaths. Most of the troops in the east and in Khost province are American. The translator was an Afghan citizen, Wojack said.
More than 60 Afghan civilians were also wounded in the bombing, the governor's office said in a statement. The city's hospital alone was treating about 30 people injured in the explosion, said Dr. Amir Pacha, a physician working there. He added there could be other victims being treated at nearby private clinics.
Taliban spokesman Zabiullah Mujahid said in text messages to media that the insurgent group was behind the attack.
The weekend firefight that led to the 2,000th U.S. death occurred in a gunfight between Afghan and U.S. forces, although both sides have conflicting accounts. It may have been sparked by a disagreement between the troops, or confusion over the source of an insurgent mortar or grenade, according to various Afghan and international officials.
Regardless of the exact catalyst, the incident illustrates how tense relations have become between international troops and their Afghan allies. So far this year, more than 50 U.S. forces have been killed in insider attacks by Afghan troops or insurgents who have infiltrated their ranks.
The insider attacks are considered one of the most serious threats to the U.S. exit strategy from the country. In its latest incarnation, that strategy has focused on training Afghan forces to take over security nationwide - allowing most foreign troops to go home in 27 months.
As part of that drawdown, the first 33,000 U.S. troops withdrew by the end of September, leaving 68,000 still in Afghanistan. A decision on how many U.S. troops will remain next year will be taken after the American presidential elections. NATO currently has 108,000 troops in Afghanistan - including U.S. forces - down from nearly 150,000 at its peak last year.
The program to train and equip 350,000 Afghan policemen and soldiers has cost the American taxpayer more than $22 billion in the past three years.