After an outbreak of Andes hantavirus on a cruise ship infected 11 people and killed three earlier this year, a review published last week in JAMA Neurology highlights the often-overlooked neurologic complications of hantavirus infection. Brain and nerve involvement is uncommon, but it can be severe and may require both acute and long-term neurologic care.
Hantaviruses are rodent-borne viruses. Most spread through exposure to infected rodent urine, droppings, or saliva; Andes virus is the only strain known to be capable of spreading from person to person.
2 clinical syndromes, many neurologic complications
Hantaviruses can develop into two major clinical syndromes—hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS)—each with distinct neurologic risks.
HPS occurs most often in the Americas and primarily affects the lungs and cardiovascular system. It has a mortality rate of 35% to 50%. Neurologic problems in HPS patients are typically secondary to critical illness and may include headache, delirium, seizures and, rarely, brain hemorrhage or postviral encephalitis, writes Avindra Nath, MD, of the National Institutes of Health, in the review.
HFRS is endemic to Asia and Eastern Russia. It manifests with fever and is more commonly associated with direct neurologic complications. A review of 811 patients with the Puumala strain of HFRS found that 97% experienced headaches, 40% reported blurred vision, and 31% experienced vomiting. About 1% developed severe complications such as meningitis or encephalitis. Rarely, patients may experience peripheral neuropathy or stroke.
One complication of HFRS is pituitary damage, which can cause hormonal problems that may not emerge until weeks or months after infection. These problems include fatigue, adrenal insufficiency, the rare disorder diabetes insipidus, sexual dysfunction, amenorrhea (lack of menstrual periods in women of reproductive age), and hypothyroid symptoms.
In one study of hospitalized patients with Puumala infection, most developed neurologic symptoms, almost half had cerebral spinal fluid abnormalities, and two had sudden vision loss because of pituitary apoplexy (sudden bleeding or loss of blood supply to the pituitary gland).
The long-term neurologic consequences of hantavirus have not been well studied, notes Nath, though one study found that, 20 years after infection, 78% of Puumala patients had persistent hypertension, and 8% had chronic kidney disease.
More studies needed on brain manifestations
Currently, there are no US Food and Drug Administration-approved antiviral treatments or licensed vaccines for hantavirus infection, though some vaccines are in pre-clinical trials. Several antiviral drugs, including favipiravir, molnupiravir, griffithsin, and ribavirin, have shown promise in early trials, but more research is needed, writes Nath.
Most of what is known about hantavirus-related neurologic disease comes from case reports and small studies. Plus, “the literature is biased toward description of severe and unusual manifestations,” continues Nath. “The infections often occur in rural settings where resources are limited; hence, it is likely that the cases are underreported in the literature.”
We need to prevent the stigma directed toward patients and contacts while simultaneously communicating the importance of isolation in controlling the spread of infection.
He calls for prospective studies with long-term follow-up to fully understand the depth of the virus’s involvement with the nervous system.
“As physicians, we also play a crucial role in communicating accurate information about the infection, addressing public fears and misinformation, and building trust with the patients, their families, and the public in general,” Nath writes. “We need to prevent the stigma directed toward patients and contacts while simultaneously communicating the importance of isolation in controlling the spread of infection.”