Good doctors are of no use without good discipline.
—Lieutenant General William Slim, British Corps commander, Burma, WWII
Even before the ink was dry on the desert pneumonia investigation report, we faced another crisis that pulled USAMRIID and the military infectious disease community together again.
In 2003, long before Ebola struck West Africa, a civil war raged in Liberia. The U.S. military launched the USS Iwo Jima Amphibious Ready Group to secure the Roberts International Airport outside Monrovia. The Twenty-Sixth Marine Expeditionary Unit on board arrived from recent deployments to Iraq and Djibouti. Before leaving the ship, each marine received aluminum-wrapped blister packs of mefloquine pills to take weekly on the honor system to prevent malaria. They also received the standard briefing on guarding themselves against mosquito bites: sleep under bed nets, spray your uniforms with the insecticide permethrin, and use insect repellents.
On August 14, 2003, nine helicopters took off from the ship’s deck and ferried 225 marines ashore. The marines set up their living quarters inside an abandoned, rat-infested airport warehouse surrounded by broken windows, standing water, and swarms of mosquitoes. The marines cleaned out the debris and swept the site to make it more hospitable, and some hung out on the roof. Anyone who knows anything about military history might have predicted the impending fiasco.
The marines spent a mere eleven days on the ground before returning to their ships. After one day back on the ship, a marine spiked a fever. Others with fever and diarrhea soon followed. Shipboard doctors gave them the antibiotic ciprofloxacin to treat presumed travelers’ diarrhea. Thus began the disaster.
Liberia happens to be a hot spot for Lassa fever, a deadly virus that causes a hemorrhagic fever like Ebola, but it is easier to catch. The discovery of Lassa fever in 1969 occurred after an incredible convergence of events and bad luck. Laura Wine, a nurse at the Lassa Mission Hospital in Nigeria, probably cared for an unrecognized victim before she developed a fever with severe fatigue, back pain, sore throat, and rash. Seven days later her kidneys shut down, her face swelled, she convulsed, and then she died. Charlotte Shaw, a fellow mission nurse, contaminated a cut on her finger with Laura’s saliva while caring for her. She soon came down with a 102-degree fever, headache, chills, and back and leg pains. Malaria pills didn’t help. Within eleven days Charlotte’s blood pressure plummeted, she swelled, and she also died. Penny Pinneo, a third nurse who cared for both Wine and Shaw, developed a low-grade fever, weakness, and dizziness. The mission doctors, recognizing a disturbing chain of transmission and afraid Penny might die, too, flew her emergently to the United States for treatment. After several grueling days of travel, she finally arrived for care at Columbia Presbyterian Hospital in New York City. Miraculously, she survived. The hospital doctors worked closely with the virology laboratory at Yale, which had received blood samples from all three nurses. After painstaking work over months collaborating with the CDC, they discovered a new virus, named Lassa after the Nigerian town of its first victims.
Field studies revealed that Lassa survives in West African rats that shed large amounts of virus in their urine and feces. Humans are infected in multiple ways: after eating food contaminated with rat urine or feces, eating the rats (a delicacy in parts of West Africa), or inhaling the virus in an enclosed area.
On Friday, September 5, an ocean away from Liberia, USAMRIID held a badly needed “morale day” for institute personnel, which included a raft expedition down the Shenandoah River in West Virginia. My clinic chief, Dr. Ellen Boudreau, decided to forgo the event and work instead, because she feared recent heavy rains might increase the risk of hazardous rapids. I had the opposite view, hoping the rains guaranteed extra excitement on the rapids.
Ellen spent a quiet morning catching up on her research paperwork back at USAMRIID. Around 3:30 p.m., USAMRIID’s headquarters patched in a call to her office from an air force major, the military flight dispatcher in Germany.
“How did you get my name?” Ellen asked. “They told me you would know something, and you were the best person around at the time,” the dispatcher said. “What can I help you with?” Ellen responded.
The dispatcher described a nightmarish scenario, with marines sleeping in a rat-infested warehouse. Now some were sick, and he had the two sickest loaded on a plane on the tarmac at the Monrovia, Liberia, airport. They thought it might be Lassa fever. Should he send them to USAMRIID?
Ellen pulled in colleague Dr. John Aldis, and the two of them engaged with the dispatcher in a series of phone calls that got their undivided attention. They couldn’t talk to anyone on the ship directly, but they relayed questions and answers through the dispatcher to the ship.
John is a family-practice doctor with a Tulane public health degree who spent ten years in the navy and then eighteen years as a U.S. embassy physician in the foreign service in places like Indonesia, the Philippines, and West Africa before coming to USAMRIID. His gray hair and wire-framed glasses give him a scholarly appearance.
“We were first trying to figure out what the fuck was going on,” John said. “I pictured in my mind five or six marines and two or three were extremely ill.” A couple of marines “were essentially dying. That news came through pretty quickly early on. Extremely sick marines” who were becoming “less and less responsive, less and less coherent.”
There was no one else around USAMRIID at the time to consult with. “The place was basically deserted,” John said. “We felt a bit lonely. This was Friday afternoon. Nobody was home. Nobody was answering phones. Nobody was helping us. It was unbelievable. Both of us slipped into our ‘tropical medicine’ mode and started with some questions. . . . Anyone with severe fever coming out of that area would have malaria until proven otherwise.”
Malaria, a known tropical scourge of military forces for centuries, gets its name from the Latin term for “bad air” because infections occurred around swamps, where the air smelled bad. But it wasn’t the air; it was the mosquitoes spreading the deadly parasite.
When female mosquitoes bite someone infected with malaria, the mosquito ingests male and female parasite forms that unite in the mosquito’s gut. After two weeks their offspring migrate to the mosquito’s salivary glands and the next unlucky person bitten gets injected with thousands of infectious parasites. The parasites travel to the liver and later escape into the blood stream. Like any parasite, they seek nourishment and devour hemoglobin, the molecule in red blood cells that carries oxygen in the bloodstream. After developing inside the cells for a couple of days, the parasites burst out, popping the red cell like a balloon, and seek new red cells to infect. This continues in waves of illness, causing patients to go through cycles of fever and shakes on successive days in synchrony with the parasite’s life cycle. Severely ill victims can go into renal failure, respiratory failure, or become unconscious before they die.
“Are they on malaria prophylaxis?” John and Ellen asked the dispatcher. “Yes, yes,” was the response. “Are we sure they’re taking it?” John asked, and Ellen nodded in agreement with his question. “Oh yes, direct observed therapy,” the dispatcher responded. “The sergeant was watching them take it.”
John had some skepticism from his own experience with marines. When his brother visited a clinic in Pleku, during the Vietnam War, he was amused to see numerous chloroquine pills, given to prevent malaria, scattered on the ground outside the clinic. “It looked like snow,” he said. The marines were “putting pills in their mouths and spitting them out when they got out of the clinic.”
Ellen thought, if they had Lassa, the Slammer at USAMRIID might be the best place for them. It was the only unit of its kind in the United States at the time, and its unique features could prevent spread of contagion in the hospital. But Liberia was at least eight hours away. The patients could go downhill fast during the flight and arrive at our doorstep circling the drain. Ellen recommended instead that the dispatcher send the two marines to Landstuhl Regional Medical Center, the closer military hospital in Germany.
Then the dispatcher said that the ship’s doctor, a general surgeon, “thinks on the blood smear he sees malarial parasites.”
“That just blew us away,” John said. “So, then everything shifted. The world turned upside down.” John’s voice quivers with emotion as he recalls what that meant: “We gotta save these lives and we can do it. Lassa, not much chance. We have to get them in treatment very, very soon. We can’t wait on a flight.”
He and Ellen insisted: “If they were put on a plane, they must be on treatment. Our feeling was if it was Lassa, starting them on malaria treatment wasn’t going to hurt them.”
But they got resistance. “Was it really necessary?” the flight dispatcher asked. He wondered why malaria was being considered if the soldiers had indeed been taking their prophylaxis.
John said, “He was a nice guy, but he was as terrified as the rest of us.” The dispatcher was worried about a very narrow flight window. “You know,” John says, “you don’t fight flight windows.”
The dispatcher had another problem. “I have a bunch of sick marines on board a ship off the coast of Liberia,” he said, “and they want me to take them to get care in the United States for their fevers. They feel that USAMRIID is supposed to be the place to take them. Are you a specialist in this area?”
“It could be several possibilities,” Ellen said, “but I’ll let you talk to the infectious disease doctor.” It just so happened, that doctor was her husband, Colonel Charles Hoke, who by now had retired from the army but who still worked for the army across the street from USAMRIID.
She hung up the phone and contacted Charles immediately. She gave him a brief rundown. Charles looked at his watch, and said, “Oh my gosh, it’s 4:30 on a Friday afternoon. Nobody’s going to be in the office” at the navy hospital in Bethesda, Maryland.
Charles called the dispatcher back. The dispatcher told him, “Don’t take a long time,” in a rude and pressured voice. “We’ve got a big problem. We’ve got to hurry. We need a decision here. You’re holding up a plane.”
While on the phone with the dispatcher, Charles thought—it’s an hour earlier in San Antonio, Texas, home of the Brooke Army Medical Center. He called the infectious disease consultant to the army surgeon general who worked at Brooke and kick-started the extensive military infectious disease network. But these were marines—they should go to a navy hospital instead. With Charles still on the phone, the doctor at Brooke immediately contacted his navy counterpart, Dr. (Captain) Sybil Tasker, on another line.
Sybil notified her hospital chain of command and her team at the National Naval Medical Center (NNMC) in Bethesda, Maryland, to prepare for admitting up to thirty sick marines.
When Charles got off the phone, he called the dispatcher back to let him know that the navy hospital was ramping up. The plane with the two sickest marines had just lifted off en route to Germany.
At the Landstuhl Regional Medical Center in Germany, Lieutenant Colonel Greg Deye, the new infectious disease doctor, got a call about two sick marines who were inbound. As many as thirty to forty might arrive on a later flight.
Oh Shit, he thought.
Greg had little time to prepare, but he spent much of that time fielding calls from generals wanting to hear the latest.
The extremely high attack rate didn’t jibe with malaria, especially for marines taking malaria pills. It had the classic hallmarks of a point-source outbreak from a common exposure—like when a whole church congregation develops fever and vomiting after eating the same tainted potato salad at a church picnic. Sybil Tasker worried about Lassa, with rat urine and feces in the warehouse as the common exposure.
One of Sybil’s colleagues at NNMC, Dr. (Captain) Greg Martin, got on speed dial with the surgeon on the ship and kept in close contact over the next twenty-four hours. The surgeon told him he had looked at a blood smear from one of the sick marines and thought he saw malaria parasites. Greg was dubious. After all, most surgeons wouldn’t know how to diagnose malaria, and the marines were taking mefloquine pills already.
Diagnosing malaria with a microscope requires two drops of blood smeared and stained on a glass slide and a trained eye to recognize its sinister beauty of signet rings or headphone shapes lit up in a splash of dark red, purple, and blue inside the hockey-puck shaped red blood cells. Some species of malaria develop tiny blue stipples or transform into basket, amoeboid, or oval forms with pointy antennae. But the surgeon had taken the military’s tropical medicine class a year earlier, where he learned how to identify malaria. So Dr. Greg Martin recommended treating the febrile marines still on the ship for malaria before they got on the plane, just in case.
Greg Martin then got into a tug of war with the air force, which said it wouldn’t risk carrying marines infected with a potentially dangerous agent like Lassa, thus contaminating and knocking a multimillion-dollar plane out of commission afterward. Greg dug in his heals and pushed the argument up the chain of command. There was no way he would leave up to forty sick marines stranded in Liberia or on ships. Greg prevailed.
Hours later, in Germany, just as the first two sick marines arrived, Dr. Greg Deye learned the other planeload of thirty to forty marines would be diverted to Washington. He breathed a sigh of relief.
It had been a beautiful, sunny day, and a good time with my USAMRIID colleagues on the rapids. Around 5:00 p.m. that afternoon, I was pulling my raft out of the Shenandoah River when my cell phone rang. Ellen Boudreau was on the line, and she briefed me about the impending disaster.
After hearing about the rat-infested warehouse, I said, “Shit, that sounds like Lassa.” The marines would have had plenty of opportunities to contact or inhale the virus. We had a stash of the only possible treatment for Lassa, an investigational antiviral drug, ribavirin, so we kept an active protocol for the occasional unlucky soldier or lab worker who might get infected. We hadn’t used the ribavirin protocol for several years, so I recommended my team “dust it off,” just in case we needed to use it.
Lassa had a track record for spreading in the hospital, but scientists had also learned the hard way that Lassa spreads just as easily inside the laboratory. In 1969 the chief lab scientist at Yale, Dr. Jordi Casals, became severely ill and nearly died. Convalescent serum, donated by Penny Pinneo, may have saved his life. One of his technicians, Juan Ramon, also became ill. Because Ramon had not worked with the virus, no one considered the possibility of Lassa until it was too late. He died. No one knew how Lassa got him, but as a result Dr. Casals moved further research with the virus to the national Communicable Disease Center laboratory (precursor to the CDC) in Atlanta. These events helped shepherd in a new era of studying such dangerous viruses in highly controlled “containment” laboratories at the CDC and USAMRIID.
Mindful of Lassa’s checkered history, Sybil Tasker didn’t want to raise a panic at NNMC during the weekend, but she had to prepare for the risk of spread within the hospital, just as one would for Ebola virus. If the marines on their way to Washington had Lassa, she considered the major cluster it would be to care for them safely, feed them, and set up guards for the ward. The team at NNMC moved boatloads of patients to empty out an entire thirty-four-bed cancer ward to isolate the ill marines.
A brand-new infectious disease fellow-in-training was in the doctors’ room at NNMC and thought he overhead one of the staff say there was a plane of inbound marines sick with “Wassa fever.” Not knowing what that was, he immediately looked it up online. The internet response, “Do you mean Lassa fever?” Oh, Lassa fever.
As the night wore on and the navy doctors went through their preparation checklists, they considered that if the marines on the hospital wards used the toilets, they could potentially excrete live Lassa virus in their urine. If that urine made it into the sewers, local mammals such as sewer rats could become infected and potentially establish the disease in the local area. The last thing they wanted to do was be responsible for bringing Lassa into the U.S. population.
So they decided to pour bleach, which was known to kill Lassa, into the toilets after the marines used them and let it sit long enough to decontaminate the water before flushing the toilets. However, incredibly enough, the hospital had no bleach because it was deemed a hazardous material.
Dr. Tim Burgess, a mid-grade navy infectious disease doctor with a shock of snow-white hair and a mischievous grin, got tagged to go out and get some bleach. So around midnight he drove to a grocery store in suburban Maryland and loaded up twenty-four gallons of bleach at the cash register. He says now, with a chuckle, “You get interesting looks if you show up in a military uniform at a grocery store at midnight and buy twenty-four gallons of Clorox bleach and nothing else.”
The mid-twenties male cashier at the checkout counter asked him, “Eh, somethin’ going on?” Tim responded, “Nah, I just needed some bleach.”
Today such a purchase might prompt a terrorism alert. At the time Tim wondered how he might explain what he was doing if stopped by the cops: “It’s a long story, there’s this Lassa fever thing . . . ,” but fortunately, he wasn’t. He concluded that many unusual things happen in grocery stores at midnight or after. This was just a new wrinkle.
Meanwhile, Dr. Greg Deye in Landstuhl Germany was joined by a military preventive medicine colleague and malaria expert, Colonel Dennis Shanks, who just happened to be visiting Landstuhl for other business. Their working diagnosis for the two sick marines was Lassa fever. When they met each other in the lab and looked at the blood smears together, Dennis suddenly said, “My God, they’ve got malaria!”
Greg immediately called NNMC to alert his colleagues there of the possible diagnosis in the arriving marines. The NNMC docs thought it was interesting but still doubted such a large outbreak could come from malaria.
At 4:00 a.m. Sunday morning, around ten army and navy doctors, nurses, and corpsmen descended on Andrews Air Force Base in Washington DC to meet the arriving military transport plane carrying the ill marines. They had gotten word in advance of a mix of illness severity among the marines, and they were prepared with a large evacuation bus for the “walking well” and ambulances for the severely ill ones. The team was ready, wearing blue hospital gowns, N95 respirator masks, gloves, and goggles to minimize any risk of spread. One of the infectious disease fellows recalls being excited and realizing how lucky he was to get this experience, but he wondered later whether he should have been a lot more nervous.
Tim Burgess, back from his midnight store run, recalls a “surreal moment” as the back of the transport airplane opened. The flight nurses and medics on the plane, who were wearing only flight suits and no hospital protective measures, took one look at the military doctors and ran back into the plane. Had the masked and gowned docs scared them away? Not so. Moments later, they returned—armed with cameras—and snapped pictures of the doctors covered head-to-toe in their gear.
As the doctors boarded the plane, one of them recalled that the MEDEVAC team and marines stared at them as if thinking that “either they were all screwed, or we were crazy.”
Even before doing complete assessments, the doctors drew blood from the sickest marines. USAMRIID Virology Division chief Dr. Tim Endy immediately drove the samples fifty miles up the road to USAMRIID to start the Lassa tests cooking.
Once in the hospital, the NNMC team decided to ferry the marines in groups up a single elevator to minimize the risk of spreading infection to others, with a plan to decontaminate the elevator afterward. They posted security guards and hospital medics on each floor to prevent other patients from using that elevator. Despite such preparation Greg Martin got a call from a nurse that a woman had just ridden up the elevator with a group of sick marines.
What?! Greg almost lost it. Would he have to quarantine a woman now for possible Lassa exposure?
The corpsman at the elevator was just trying to help the woman and hadn’t wanted to keep her waiting for an elevator.
The infectious disease team set to work trying to diagnose the cause of the marines’ fevers. In addition to Lassa and malaria, they considered the long list of tropical diseases that cause fever, including leptospirosis and rickettsial diseases. An experimental rapid test for malaria on ten of the marines popped up positive, providing the first indication at NNMC that some had malaria.1
Word of the disaster spread through the military channels and up to Colonel Bob Defraites, lead preventive medicine doctor at the army surgeon general’s office. Bob, who had a long track record in field operations, sent out a prescient email: “Worried about Lassa, thinking malaria.”
Later Sunday morning I received a phone call from Tim Burgess. Bad news. Some marines at NNMC were now severely ill, requiring breathing tubes, ventilators, and vasopressors to maintain their blood pressure. One marine with severe lung disease on 100 percent oxygen and a ventilator didn’t look like he would make it. The team dictated an imminent death medical board and brought his mother into the room, informing her that he would probably die in a couple of hours.2
By this time the team had diagnosed most of the marines with malaria, but not all the puzzle pieces fit yet. The marines had been taking mefloquine. Why didn’t it work? Could they have a resistant strain? Could the sickest marines be infected with both Lassa and malaria? The navy docs wanted to implement the ribavirin protocol just in case. The last thing they wanted was for the marines to survive malaria, only to die from Lassa.
I told Tim I would get the ball rolling and would meet him at USAMRIID, so he could pick up the ribavirin protocol and the drug.
It seemed simple enough . . . but not so.
I recalled approving the latest revisions to the protocol about a year earlier, and I believed that it had proceeded on its pathway through the system to approval by the FDA, which was required because ribavirin was not licensed for Lassa. However, when I asked my team for the protocol, they couldn’t find the latest version.
What the hell? Where was the protocol?
After immediate scrambling and phone calls, we figured it out. The protocol had left USAMRIID, but it got lost on someone’s desk at its next stop at the regulatory office at Fort Detrick. It had never made it to the FDA.
Damn! This was a major screwup.
I blamed myself for not tracking this, but there was plenty of blame to go around. After getting over our momentary panic and shouting numerous expletives, we regrouped to come up with a solution.
Fortunately, there was another way to use the drug. We picked up the phone and called the FDA person on call. After some back-and-forth, the FDA authorized emergency use of the drug (as an “emergency IND”). This didn’t take too long because we already had procedures for administering the drug and we just needed the FDA’s blessing. But we had egg on our faces and were embarrassed.
Fortunately we were beginning to get a better handle on what had happened. The patients started to improve on malaria treatment. One of the sickest marines at the hospital in Landstuhl appeared to have “Blackwater fever,” a known complication of severe malaria. Everything pointed to malaria. The missing piece of the puzzle fell into place when Congressman John Murtha, an ex-marine himself, visited the marines on the hospital ward and the ICU. One marine confided that he and his buddies hadn’t been taking their malaria pills.
Sunday night, when the Lassa tests on thirty-two marines came back negative, Sybil Tasker breathed a sigh of relief and felt as if a weight had been lifted off her shoulders. She no longer had to worry about the risk of infection spreading to others and all the logistic challenges that raised. The woman on the elevator Greg Martin had heard about would not need to be quarantined.
In the end thirty-six marines were treated on the ship, and forty-four marines were treated in the hospital for proven or suspected Plasmodium falciparum—the deadliest form of malaria. It was the largest outbreak of malaria in the U.S. military since the Vietnam War.
We all had dodged a bullet. No Lassa. “Only” malaria. That is like saying, “Whew, it wasn’t a pipe bomb, just a hand grenade.” Fortunately, all the marines survived—even the sickest ones, possibly because of starting malaria treatment before their arrival at the hospital.
Diseases and nonbattle injuries have caused more warrior casualties on the battlefield than bullets and bombs. Malaria usually ranks as the top or second-highest infection threat, and it has weighed heavily on U.S. military campaigns since the Revolutionary War. As a result the military has played a key role in developing all malaria drugs used in the United States—out of necessity, because of the tropical locations where military personnel are often deployed. During World War II malaria sidelined over five hundred thousand U.S. forces in Southeast Asia and the Pacific islands. General Douglas MacArthur told the army’s top malaria expert at the time, “It’s going to be a very long war if for every division I have facing the enemy, I have one sick in the hospital and another recovering from this dreadful disease.”
As Lieutenant General William Slim, the British Corps commander during the 1943 Burma campaign, observed, “Good doctors are of no use without good discipline. More than half the battle against disease is fought, not by the doctors, but by regimental officers.” By 1943–44 General Slim could measure blood levels of Atabrine, a drug to prevent malaria, so he held his commanders accountable for noncompliance among their ranks. “I only had to sack three,” he said. “By then, the rest got my meaning.”
Any military campaign in a tropical region of the world must contend with malaria. Dr. Dale Smith, historian at the Uniformed Services University, says, “Malaria will destroy an army, but it won’t stop a war. Man’s capacity to kill each other exceeds his capacity to feel ill.”
There were several heroes in this story, especially the ship surgeon who recognized the parasites, which kick-started early malaria treatment for some of the marines. Also, like the desert pneumonia story, the linkages in the military infectious disease community across the globe helped.3 Being able to pick up the phone and connect with a person you know on the other end makes a world of difference for sounding the alarm. The personal connections between army and navy physicians, USAMRIID and the hospital, and the navy hospital with its fleet all worked together to avoid what could have been a bigger disaster.
Every military disaster requires an “after action report.” Dr. Charles Hoke calls the event the “4M Disaster,” for marines in Monrovia with malaria who failed to take their mefloquine—a medical crisis “perfect storm.” The investigation into how this chain of unfortunate events happened revealed that of the forty-four affected marines queried, few used simple measures to reduce their chances of mosquito bites: only nineteen (45 percent) used insect repellent, five (12 percent) used repellent-treated clothing, and none used bed nets. This was no surprise because no bed nets went ashore with the marines, and the shipboard stocks of permethrin for treating uniforms had been depleted. Although twenty-three (55 percent) said they complied with taking their preventive malaria pills, only a shocking four (10 percent) had levels in their blood high enough to prevent malaria. Most who admitted not taking the medicine said they just forgot.4 The prior deployments to areas with lower malaria risk in Iraq and Djibouti may have lulled the marines into a false sense of security and lack of awareness of the dangers awaiting in Liberia. As General Slim in the Burma campaign recognized, getting military personnel to take malaria pills only works if you watch them.
Fortunately, we occasionally learn from our failures. During the deployment to Liberia for the 2014–16 Ebola response (“United Assistance”), our experience was significantly different from the one eleven years earlier. Unit commanders required daily enforcement of taking malaria pills. The “fear factor” probably helped. Any of our soldiers who developed a fever in-country would be labeled a “possible Ebola” patient until proven otherwise. No one wanted to risk being stuck in isolation or shipped back to the United States for not taking his or her malaria pills. Sometimes other disincentives for noncompliance can improve compliance. The result was the most successful malaria prevention campaign in the history of U.S. forces. Some of the lessons from managing the marines with suspected Lassa in 2003 helped shape future design modifications at the hospital when Ebola struck in 2014–16.
So maybe we have learned something, but I can say with confidence that this isn’t the last we’ll hear of malaria and the military. Until we have a licensed vaccine that works, as memories of the disasters fade, more seasoned experts leave the military, and the malaria parasites become resistant to more antimalarial drugs, it is only a matter of time until the U.S. military is humbled again by malaria. Guaranteed.