Lassa fever and the first “Hot Zone”

Long before anyone ever heard of Ebola virus or nervously read Richard Preston’s

gripping 1995 account of Ebola outbreaks in darkest Africa and nearby Virginia, there was Lassa

fever, and dead missionaries, and dying Yale scientists, and a dramatic book called Fever: The

hunt for a new killer virus. The two tales, told 25 years apart, have much in common. A

mysterious illness. Sudden, gruesome deaths. The scientific search for the culprit and a cure.

Accidents and heroics. It’s a twice-told tale that surely will be repeated.

In 1969, Lassa was an obscure village in northeast Nigeria. It probably would have

remained obscure, but for three desperately ill nurses at the mission hospital. Two of them,

Laura Wine and Charlotte Shaw, died. The third, Lily Pinneo, was airlifted to New York. Blood

samples from her and her two dead colleagues were sent to the famous Yale Arbovirus Research

Unit (YARU) in Connecticut.

In an ironic twist, those blood samples eventually would reveal a new and deadly virus,

kill a lab technician and save the life of a Yale physician.

The virus found by the YARU researchers turned out to be a new RNA virus normally

found in West African rats. The virus is transmitted to people through contact with rodent urine

and droppings, contaminated aerosols, and direct person-to-person contact. That last route is

common is hospitals and clinics where staff may come in contact with bodies, blood and vomit.

That’s how the three missionary nurses were infected: caring for patients and

participating in autopsies. But how Juan Roman (the lab tech) and Jordi Casals (the YARU

physician) were infected is still a mystery. They had used the nurses’ blood to inoculate mice in

an attempt to grow more virus for experiments. At some point they may have been exposed to

virus-laden aerosols created by the caged mice. In any case, Roman died from Lassa fever.

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Casals was saved by Lily Pinneo’s blood serum, which contained neutralizing antibodies against

the virus.

The accidental infections scared everyone and halted YARU’s work on the virus. On

February 10, 1970, Lawrence Altman’s normally staid New York Times headline screamed, “New

Fever Virus So Deadly That Research Halts.”

The mortality rate from Lassa is estimated to be 15-20%. Symptoms include fever as

high as 107F, mucosal ulcers, a hemorrhagic rash, pneumonia, back pain, vomiting, and cardiac

and kidney complications. Survivors often experience some degree of deafness. Intensive care

and an antiviral drug called Ribavirin are the only treatments available.

If this story seems like ancient history, it’s not. Just last month, an outbreak of Lassa

killed seven people in northern Liberia. The World Health Organization estimates there may be

300,000 to 500,000 annual cases and 5,000 annual deaths across West Africa.

And if it seems like an African problem, it’s not. It’s a potential worldwide problem

caused by jet planes.

In 1989, for example, a 43-year-old Nigerian engineer living near Chicago flew home

from his mother’s funeral in Nigeria. She had died from an unidentified febrile illness. After

returning to the U.S., he began to feel ill and visited a clinic. It was flu season and no one paid

much attention to his symptoms. Days later, he returned to the clinic in much worse shape.

Eventually, a history of his travels and his mother’s death led a few people to suspect Lassa. The

man died before he could receive Ribavirin. Lassa was later confirmed, and the 102 people he

came in contact with during the time he was infectious were tracked down. Fortunately, none of

them were infected.

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 It happened again in New Jersey in 2004. A 38-year-old businessman traveled through

Liberia, Sierra Leone, the U.K. and the U.S. Within hours of arriving home in Newark, he was

hospitalized and died several days later. After Lassa was confirmed, the Centers for Disease

Control (CDC) issued a health advisory and tracked down 188 people who might have had

contact with him on the flight or on the ground. Five “high risk” family members were

monitored for any signs of illness, but again, no one else fell ill.

It’s a small world and we crisscross it in hours in the company of stowaway microbes.

Germany imported a case of Lassa from a 68-year-old Sierra Leone resident last July and

two cases in 2000. Other cases have been imported into the Netherlands and the U.K.

A quarter of a century after Lassa fever broke out of Africa and the YARU labs there is

now an experimental vaccine that protects against the virus. It is effective in protecting lab

monkeys. Whether it is ever licensed for use in humans is uncertain, but the people who lived

through the harrowing months of 1969-1970 in Nigeria and Connecticut would probably like to

see the vaccine licensed.