Recognizing Early Signs of Rabies: What to Watch for During the Incubation Period

Dear Dr. Hsiao: If a patient unfortunately contracts rabies, are there any unusual signs that can be detected during the incubation period before the onset of early symptoms?

In 2017, a female patient in Xi'an, China, experienced frequent urination, urgency, numbness in the leg where she was bitten by a dog, and back pain after more than 20 days post-bite.
After consulting local orthopedic and urology departments without improvement, her condition worsened over three days, and she was diagnosed with rabies the following day, ultimately leading to her death.
The patient had received four doses of the rabies vaccine on schedule prior to the onset of symptoms.
This raises the question of whether there are warning signs during the incubation period that could alert the patient to seek urgent care before entering the prodromal phase of symptoms.
There are also claims online that if a wound from a cat or dog bite appears healed but still hurts, it could be a warning sign.
Additionally, some people have stated that the rabies virus is not very potent and that transmission only occurs if the wound bleeds.
Furthermore, could you clarify what a 40% incidence rate means? Does it depend on the severity of the wound and the amount of virus exposure? Thank you for your insights.

Luka, 30~39 year old female. Ask Date: 2020/04/15

Dr. Xiao Yongxun reply Family Medicine

In 2017, a female patient in Xi'an, China, developed frequent urination, urgency, numbness in the leg where she was bitten by a dog, and back pain after more than 20 days post-bite.
After seeing local orthopedic and urology specialists without improvement, her condition worsened over three days, and she was diagnosed with rabies the following day, ultimately leading to her death.
The patient had received four doses of the rabies vaccine prior to the onset of symptoms.

Research indicates that the rabies virus travels from the site of the wound along the nerves to replicate in the spinal cord and brain, at a rate of several millimeters per day.
In theory, early symptoms may include localized paralysis or pain; once the virus reaches the central nervous system, typical rabies symptoms manifest.
This means that when a person or livestock is bitten by a rabid animal, the virus in the saliva enters the body through the wound; it first replicates in the muscle and binds to nicotinic acetylcholine receptors in peripheral nerves, eventually reaching the central nervous system.
Negri bodies can be observed in ganglion cells and ganglia.
Once the virus reaches the spinal cord, the brain quickly becomes infected, leading to severe neurological symptoms with a mortality rate approaching 100%.

Initial symptoms may include nonspecific clinical signs such as fever, sore throat, chills, malaise, anorexia, vomiting, difficulty breathing, cough, weakness, and headache, or specific symptoms at the bite site.
Days later, symptoms of agitation and fear may appear, followed by paralysis, difficulty swallowing, and muscle spasms in the throat, leading to hydrophobia, and subsequently, confusion and seizures.
In the late stages, patients often die from respiratory paralysis within 2 to 6 days.

Regarding the case in Xi'an, more detailed information is needed to understand whether it was too late for vaccination, if the vaccine quality was poor, or if other factors were involved.
Therefore, it is not advisable to jump to conclusions.

Does this imply that during the incubation period, there are warning signs that could alert the patient to seek urgent care before the onset of prodromal symptoms? Once rabies manifests, the mortality rate is nearly 100%.
Thus, clinically in rabies-endemic areas such as China, Southeast Asia, the Middle East, and Africa, it is better to administer complete post-exposure prophylaxis rather than just observing symptoms after being bitten by a mammal.

There are also claims online that if a wound from a cat or dog appears healed but still hurts, it is a warning sign.
Additionally, some people have posted that the rabies virus is not very threatening and that it must cause bleeding to be transmissible.
Theoretically, a wound may heal within a few days while the rabies virus has already invaded the nervous system.
There is no medical basis for determining the risk of rabies transmission based solely on whether a wound bleeds; without comprehensive research, I do not recommend adopting this belief.

What does a 40% incidence rate mean? Is it determined by the severity of the wound and the amount of viral exposure? I am not aware of what "40% incidence rate" refers to, let alone whether it is based on the severity of the wound and the amount of viral exposure.
Given the many claims circulating online, I recommend visiting the official website of our country's Centers for Disease Control, which provides a more comprehensive statement on rabies, or discussing this with your family physician.

Reply Date: 2020/04/15

More Info

Rabies is a viral disease that is almost universally fatal once clinical symptoms appear. Understanding the early signs during the incubation period is crucial for timely intervention. The case you mentioned highlights the importance of recognizing potential warning signs that may indicate the onset of rabies, even before the classic symptoms manifest.

Incubation Period and Early Signs
The incubation period for rabies can vary widely, typically ranging from a few weeks to several months, depending on factors such as the location of the bite, the severity of the wound, and the amount of virus introduced into the body. During this period, the virus travels along peripheral nerves toward the central nervous system, often without causing noticeable symptoms. However, some early signs may be observed, which can serve as critical indicators for medical intervention.

1. Localized Symptoms: As you noted, symptoms such as pain, tingling, or numbness at the site of the bite or injury can be significant. These sensations may indicate that the virus is affecting the nervous system. If a patient experiences unusual sensations in the area of the bite, it is essential to seek medical attention immediately.

2. Systemic Symptoms: Other early signs can include fever, malaise, headache, and gastrointestinal symptoms. These can be nonspecific and may resemble other viral infections, which can lead to misdiagnosis. However, if these symptoms occur in conjunction with a recent animal bite, they should raise suspicion for rabies.

3. Behavioral Changes: Rabies can also cause changes in behavior, such as anxiety, confusion, or agitation. In some cases, patients may exhibit hydrophobia (fear of water) or aerophobia (fear of drafts or fresh air), which are more specific to the disease but may not appear until later stages.

Importance of Vaccination
In the case you mentioned, the patient had received post-exposure prophylaxis (PEP) with rabies vaccines. This is crucial because the rabies vaccine is highly effective at preventing the disease if administered promptly after exposure. However, if the vaccine series is not completed or if the patient is immunocompromised, the risk of developing rabies increases. It is essential to follow the vaccination schedule strictly and report any unusual symptoms to healthcare providers immediately.

Misconceptions About Rabies Transmission
There are several misconceptions regarding rabies transmission. It is important to clarify that rabies can be transmitted through bites that break the skin, but it can also be transmitted through scratches or open wounds if saliva from an infected animal comes into contact with them. Therefore, any exposure to potentially rabid animals should be taken seriously, regardless of the severity of the wound.

Understanding the 40% Mortality Rate
The statistic you mentioned regarding a 40% mortality rate refers to the likelihood of developing rabies after exposure to the virus, particularly if the exposure is not treated with PEP. The actual risk of developing rabies depends on several factors, including the type of animal involved, the location of the bite, and the amount of virus introduced. For example, bites from bats or wild carnivores carry a higher risk than bites from domesticated animals that have been vaccinated against rabies.

Conclusion
In summary, recognizing early signs of rabies during the incubation period is critical for timely intervention. Symptoms such as localized pain, systemic signs, and behavioral changes should prompt immediate medical evaluation, especially following an animal bite. Vaccination remains the most effective preventive measure, and any exposure to potentially rabid animals should be treated with caution. If you or someone you know has been bitten or scratched by an animal, it is vital to seek medical attention promptly, even if the wound appears superficial.

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