The world’s first rabies patient cured: suspended for 10 days and deceived a 100% lethal virus

Wisconsin Children's Hospital, Dr. Willoughby sits at his desk, frowning.

He must make a difficult decision, and this decision will immediately affect the life and death of a girl in the ICU.

Tremors, limp body on the left side, drooling, persistent high fever, viral infection... the girl got rabies. Without vaccination, once rabies develops, the fatality rate will be 100%.

But Dr. Willoughby was reluctant to give up easily. He had a bold idea: hibernation.

Drugs allow the brain to enter a "low energy consumption" state, thereby effectively reducing the incidence of rabies complications in the brain and reducing nervous system damage. At the same time, the patient's immune system continues to function. If during this time, the patient's immune system can produce enough anti-rabies antibodies, the virus can be eliminated. In other words, he wants the girl to "fake death" to conduct an "immunity race" to deceive the virus.

However, this method has never been tried by humans, or even tried in animal experiments, and the chance of success is almost slim. Patients are still very likely to become "vegetative" and bear the risk of serious complications.

Is it to wait quietly for death, or to give it a go?

Fight against 100% lethality

Back to Halloween a few days ago, Milwaukee had already ushered in the first snow.

On such an ordinary day, Willoughby met an unusual patient, Jenna.

Jenna noticed occasional tingling pains in her left hand and double images in front of her eyes; then dizziness, nausea and nausea appeared again. Jenna's parents also noticed that their daughter's eyes were getting more and more awkward, and it looked like the picture below.

Bilateral abducens nerve palsy (Source: Reference 8)

The family doctor performed an MRI for Jenna and found no abnormalities. But Jenna's condition deteriorated further: a high fever suddenly appeared, and the left half of her body could not move.

When Dr. Willoughby first saw Jenna, she appeared in a wheelchair. After physical examination, Willoughby found that Jenna had tremor and paresis on the left side of her body. Routine and biochemical tests of cerebrospinal fluid showed that she was infected with a certain virus, but all the virus test results were negative.

Jenna, who was getting worse, was admitted to the ICU, and her mouth began to gurgle bubbles.

Between lightning and flint, Dr. Willoughby suddenly realized: extremely atypical neurological symptoms, drooling, fever, viral infection-Jenna got rabies!

Indispensable to the diagnosis of rabies is the medical history, but Jenna's parents denied that their daughter was bitten by a dog.

Not a dog bite, what is that?

It turned out that more than a month ago, Jenna went to church as usual. A bat hit the ground. Out of curiosity, Jenna picked up the bat and carried it to the church door.

Just as she was about to release the bat, the bat left a mark on Jenna's left index finger that changed her life: a bloodstain of 5 mm long.

The CDC found antibodies to rabies in Jenna's cerebrospinal fluid and blood, and Jenna was diagnosed.

5 mm bite mark (Source: YouTube)

Rabies has shocked countless doctors.

After being infected by a diseased animal, the patient showed symptoms after an incubation period as short as one week and several years. At the onset of the disease, the patient will be extremely excited and even violent, as well as a specific "hydrophobia".

Rabies patients usually die from organ failure caused by damage to the nervous system. However, pathological studies at the time found that the brain damage of rabies patients was not caused by the direct attack of the rabies virus on the brain, but was a complication of the disease.

If there is a switch that can suspend the function of the brain and protect the brain from complications, while maintaining the normal functioning of the immune system and attacking viruses, is there any hope for Jenna to be saved?

One of the hypotheses about the death of rabies is "neurotransmitter disorder." The core view is that the biological molecules in the patient's brain cannot balance each other and cause death. Animal experiments have shown that ketamine, which is an NMDA receptor antagonist, seems to be a bridge to balance the neurotransmitters of rabies patients.

Faced with a 100% fatality rate, Willoughby had the bold idea at the beginning of the article: hibernation.

To bet or not, Dr. Willoughby gave the decision to Jenna's parents.

Dr. Willoughby (Source: YouTube)

An "immune race" to deceive the virus

The parents who love their daughter eagerly choose radical therapy, and give it a go for their daughter.

As the injections of midazolam and ketamine slowly entered the bloodstream, Jenna's "hibernation" began.

The beginning of treatment does not mean smooth sailing, on the contrary, it is actually the beginning of violent storms.

Jenna in "Hibernation" is like a boat floating in a calm sea, and may die at any time because of the sudden attack of the "big wave" of rabies.

Not long after the treatment started, Jenna developed metabolic acidosis and hemolysis caused by overdose, accompanied by autonomic disorders.

In order to prevent Jenna from being completely overwhelmed by the drug and becoming a vegetable due to excessive sedation, Willoughby must always pay attention to the changes in the EEG. With the adjustment of the drug dose, Jenna's vital signs return to stability.

The turnaround occurred on the 7th day, and the titer of anti-rabies virus antibodies in Jenna's serum began to rise gradually.

Willoughby reduced the amount of ketamine on the 8th day and replaced the short-acting midazolam with the more long-acting diazepam. He wanted to make the last effort for the victory of this gamble and remove Jenna from "hibernation." "Woke up.

Jenna in the ICU Source: YouTube

On the tenth day, Jenna opened her eyes.

But Jenna's loose eyes made Dr. Willoughby quite entangled: Does this mean that she really woke up, or because of the neurological disorder after the treatment failed, causing the muscles to twitch involuntarily and opening her eyes?

To figure this out, Willow brought Jenna's mother into the ICU and came to Jenna's bed. If the treatment is successful, Jenna's attitude may change when she sees someone she is familiar with.

The moment her mother took off the mask, Jenna's eyes blinked faster-their bet was successful!

After 31 days of hospitalization, Jenna's internal virus test turned negative. After 76 days in the hospital, Jenna was discharged with neurological sequelae such as dystonia and chorea.

Jenna is discharged. Source: YouTube

After being discharged from the hospital, Jenna still needs a long time for rehabilitation.

Jenna in rehabilitation. Source: YouTube

Jenna is like a "big kid", walking, eating, writing, and talking, all of which need to be learned again. After long-term unremitting efforts, Jenna gradually returned to a normal life, admitted to university and graduated successfully.

In 2016, Jenna gave birth to twins and became a mother.

Source: YouTube

Milwaukee Therapy Controversy

With Jenna’s successful precedent, Willoughby’s Medical College of Wisconsin summarized this treatment method as the "Milwaukee Protocol", encouraging more clinicians to use this method to treat rabies patients and actively take cases. report.

The case of Jenna became a dawn for rabies treatment. Under the large-scale media reports, the rabies that once shocked clinicians seemed to become a paper tiger overnight.

But is this really the case?

A later article published by Willoughby showed that the Medical College of Wisconsin continued to track the doctors who used Milwaukee therapy and the cases they reported. As of 2015, only 7 of the 48 rabies patients who received the therapy were alive.

Willoughby believes that although some patients tried Milwaukee therapy, the treatment failed due to the lack of a strong intensive care team in the hospital. In addition, high-quality nursing team, nutrition support team, and drug reserve resources are also indispensable for the successful development of Milwaukee therapy.

Spent a lot of effort and big price can only get a low success rate, which makes the voice of opposition to Milwaukee therapy endless.

Source: Related papers

Some scholars believe that only the rabies virus carried by bats is saved by Milwaukee therapy, which is relatively weak.

An article by The Lancet analyzed rabies viruses transmitted by different animals and found that the causes of rabies viruses in different hosts are very different. The rabies virus transmitted by bats may not even affect the central nervous system at all.

In my country, Shenzhen Hospital of Southern Medical University tried Milwaukee therapy to treat a rabies patient in 2017. After persisting in the ICU for a month, the family chose to give up treatment. This rabies patient ultimately failed to become the first person cured in China, and unfortunately passed away.

Although the curative effect is controversial, Milwaukee therapy, as the last life-saving straw in the treatment of rabies, has also harvested a group of doctors to become its solid fans.

"As a doctor, if I don't take any measures, the patient will definitely die." said a Filipino doctor who actively promotes Milwaukee therapy.

"This method really lacks evidence-based medicine verification, and the failure rate is extremely high. But in the face of the reality that rabies is 100% fatal, before more advanced treatments are available, besides using this radical method, is there any Is it a better choice?"