What is Hantavirus Pulmonary Syndrome?
Hantavirus pulmonary syndrome (HPS) is an uncommon but serious lung disease that causes fluid build-up in the lungs, low levels of oxygen in the blood, and low blood pressure. It’s caused by viruses belonging to the Orthohantavirus group and the Hantaviridae family. Two different forms of diseases are linked with these viruses.
The first form is Hemorrhagic fever renal syndrome, which features sudden kidney failure, low blood platelet count, fever, and low blood pressure. This disease is primarily seen in Asia, Eastern Russia, and some parts of Europe, and is commonly caused by virus species named Hantaan, Dobrava, Seoul, and Puumala.
The second form, HPS, is characterized by fever, muscle pain, and severe breathing problems. This disease is mostly found in North and South America and is usually caused by the Sin Nombre virus in North America and the Andes virus in South America. Patients often need help with breathing machines, and even if they receive right timely care, the death rate can be as high as 40%.
Both diseases involve breathing in the virus and can affect the lungs and kidneys. They also both can lead to a leaky blood vessel, abnormal blood clotting, and overactive immune responses. Over 24 different Hantaviridae viruses can cause diseases in humans, and the type of virus mostly depends on the geographical location and the animal carrying the virus. The viruses are primarily carried by rodents who show no symptoms, and are passed onto humans through inhaling particles from urine or feces of these animals, or rarely, through their bite. There is currently no specific cure for these diseases. The best chance of survival is through supportive treatments and reducing contact with rodents, as they are often the main carriers of these viruses.
Researchers have updated the scientific naming of these viruses in 2016 due to new information about their genetic makeup. The older name, Hantavirus, was changed to the family name, Hantaviridae, and Orthohantavirus is now used as the group name. In this article, we refer to it as “Hantavirus.”
What Causes Hantavirus Pulmonary Syndrome?
Hantaviruses were first found in the 1950s during the Korean War and were given their name from the Hantaan River where most cases at that time were reported. In North America, the most common type of this virus, called the Sin Nombre virus, is usually transmitted by the deer mouse and is mainly seen in the southwestern United States. The Sin Nombre virus was discovered after an outbreak of hantavirus happened in 1993. In South America, the most common hantavirus is the Andes virus. This virus is particularly harmful and unique because it’s the only strain of hantaviruses known to spread from person to person.
Hantaviruses are a type of virus with a protective outer coat and an RNA center. RNA (ribonucleic acid) viruses use RNA, not DNA, to multiply. The virus consists of components such as a large viral segment, a precursor to glycoproteins (a type of protein), and a nucleoprotein. The actual virus particle can vary in size. Hantaviruses invade certain types of cells like endothelial cells, epithelial cells, dendritic cells, and lymphocytes by sticking their glycoproteins to the receptors on the surfaces of these cells.
Immature cells, specifically dendritic ones, likely act as transporters for the virus into lymphatic tissue and further facilitate the replication of the virus in regional lymph nodes. Once they come into contact with endothelial cells, they trigger immune responses specifically by CD8+ T cells and macrophages.
Unlike some other viruses that cause hemorrhagic fever, hantaviruses cause the infected dendritic cells to mature and trigger a strong response from T-cells in the early infection phase. Important receptors, called beta-3 integrins, regulate platelet activation and vessels’ permeability and aid hantaviruses’ entry into the cells. Invasion of the interior lining of the vessels by the virus likely causes the production of interferon-alpha (IFN-α), which could be why prodromal symptoms appear. Prodromal symptoms are the early signs of a disease before it fully develops.
As the infection progresses, specific immune cells called immunoblasts might be seen in a blood smear. T cells become hantavirus-specific. Activated macrophages, cells that engulf harmful particles, along with these immune cells, will move towards the lung tissue space. Increase in capillary endothelial permeability follows after secretion of substances like tumor necrosis factor-alpha (TNF-α), IFN-γ, and nitric oxide, resulting in fluid buildup in the lungs. These same mediators are speculated to cause heart muscle depression in this infection, which results in a state of shock where the heart isn’t pumping enough blood to meet the body’s needs.
Risk Factors and Frequency for Hantavirus Pulmonary Syndrome
Hantavirus Pulmonary Syndrome (HPS) is the main type of Hantavirus syndrome found in North and South America. In the United States, cases of Hantavirus have been noted from the east coast in Maine to regions west of the Mississippi River. As of January 2017, most of the 697 reported cases have occurred west of the Mississippi. The states with the highest number of cases, making up around 70% of all cases in the U.S., include New Mexico, Colorado, Arizona, California, Washington, Texas, and Montana.
- Different strains of Hantavirus and their primary carriers and regions are:
- Sin Nombre Virus in Canada and the United States, mainly carried by Peromyscus maniculatus rodents.
- New York Virus in the eastern United States, from the rodent Peromyscus leucopus.
- Monongahela Virus in eastern United States, carried by Peromyscus maniculatus nubiterrae.
- Bayou Virus in the southeastern United States, found in Oryzomys palustris rodents.
- Black Creek Canal Virus in Florida, United States, from the rodent Sigmodon hispidus.
- Laguna Negra in Paraguay and Bolivia, carried by the Calomys laucha rodents. This is the first South American Hantavirus isolated.
- Andes in Argentina, Chile, and Uruguay, the only Hantavirus transmitted from person-to-person, found in Oligoryzomys longicaudatus rodents.
- Oran in northern Argentina, commonly causes disease in cane-growing areas, and originates from Oran longicaudatus rodents.
- Choclo in Panama, carried by Oligoryzomys fulvescens.
- Rio Mamore in Peru, from the rodent Neacomys spinosus.
- Lechiguanas in Argentina, found in Oligoryzomys flavescens rodents.
About half of Hantavirus infections are believed to stem from exposure in or around the home, 10% are workplace-related, and 5% occur during recreational activities. The remaining cases arise from mixed or unknown exposure sources.
Signs and Symptoms of Hantavirus Pulmonary Syndrome
This illness usually affects people who have been in contact with rodents, their droppings, or who have been bitten by a rodent. It’s especially common in farmers, forestry workers, or anyone exposed to areas infested by rodents. Other people who share their environment with them could also be at risk.
After exposure to the virus, the illness usually starts showing symptoms between 7 and 39 days. The symptoms at the start are general and similar to the flu; common complaints include headache, muscle pain, vomiting, and abdominal pain.
About 3 to 6 days following the initial stage, the person’s ability to breathe might suddenly get worse. This can happen within 48 hours and can quickly lead to a complete failure to breathe. This stage is characterized by difficulty in breathing, fluid in the lungs, low blood pressure, and shock. A chest X-ray would typically show broad-spread fluid in the lung tissues. A complete collapse of the cardiovascular system can also occur during this stage.
- Difficulty breathing
- Fluid in the lungs
- Low blood pressure
- Shock
- Possible complete cardiovascular collapse
Due to the severe infection, patients also often develop metabolic acidosis, which can lower the pH in your body and make your body produce too much acid. This serious condition of the respiratory system is fatal for 50 to 70 percent of the patients who experience it.
Other symptoms might include a decrease in urine output, small red or purple spots caused by bleeding into the skin, and other forms of bleeding.
Testing for Hantavirus Pulmonary Syndrome
When it comes to chest x-rays, about one-third of patients may initially show signs of fluid build-up in both lungs. However, after 48 hours of admission, almost all patients will show signs of fluid leakage into the tissue around the lungs. Many patients will also develop clouding in the lower parts of both lungs, or around the central part of the lungs, accompanied by some level of fluid build-up around the lungs.
A drop in blood platelet count may be detected once a patient is admitted, which can not only provide a better understanding of the disease stage but also help forecast the course of the disease. Other noteworthy lab results may include an increase in specific immune cells and abnormal white blood cells, as well as elevated red blood cell volume.
If the patient requires hospitalization, further blood tests may show immature white blood cells, a severe drop in blood platelet count, and abnormally low carbon dioxide in the blood. The patient may also have low sodium levels, slightly extended clotting time, a reduced protein level, mildly elevated bad cholesterol level, and microscopic blood in the urine. The diagnosis can be confirmed through specific immune-based tests. Ideally, a test that detects specific immune molecules (Immunoglobulin M) is used. An alternative could be a test that measures the DNA of the infectious agent.
Treatment Options for Hantavirus Pulmonary Syndrome
Treatment for this condition generally involves supportive care, focusing heavily on maintaining heart and lung function. Specific aspects of the treatment include:
Patients are often driven to seek medical treatment due to the severity of symptoms. However, medical tests often don’t find anything that would require hospital admission. As a result, treatment usually involves supportive care and patients are sent home.
About 40% of patients with this condition experience severe respiratory failure, which requires mechanical ventilation or assistance with breathing.
The University of New Mexico has had success with using an advanced treatment technique called extracorporeal membrane oxygenation. They’ve seen a 70% success rate with this approach when implemented early. However, this condition is rare, so there haven’t been large-scale clinical trials to confirm effectiveness.
Even with treatment in intensive care units, about one-third of patients unfortunately pass away within the first 48 hours after being admitted to the hospital.
Almost half of the people admitted to the hospital with Hantavirus can avoid needing to be intubated, which involves inserting a tube into the windpipe to help with breathing. This is possible if they are carefully monitored and given precise amounts of fluids.
An antiviral medication called Ribavirin has been suggested as a possible treatment method. While some benefits have been shown when the medicine is inhaled, its overall effectiveness still needs to be confirmed.
Doctors may use inotropic agents, which are medications that modify the speed or force of heart contractions, early in the treatment process. Medical professionals make an effort to maintain a healthy balance of fluids within the body, as this can support heart function and decrease lung swelling.
In severe cases, patients may encounter a condition known as disseminated intravascular coagulation – this includes severe bleeding and a drastic increase in the number of white blood cells. However, if patients show signs of improvement within the first few days, they’re likely to be removed from breathing assistance within a week.
While vaccines have been developed and used in countries like China and Korea, the long-term effects of these vaccines are still unknown.
What else can Hantavirus Pulmonary Syndrome be?
Acute Respiratory Distress Syndrome is a severe lung condition that needs immediate attention. Some of the signs to look out for include:
- Sudden shortness of breath
- Non-cardiogenic infiltrates present in the chest x-ray
- An oxygen level (PaO2/FiO2) less than 300 in arterial blood
It can be tricky to distinguish this syndrome from Hantavirus, which has similar symptoms. It is critical to identify the factors that triggered the illness. The treatment for both conditions mainly involves respiratory support.
Mycobacterial Pneumonia, on the other hand, may necessitate the use of a ventilator. If a bronchoalveolar lavage (a procedure that retrieves a sample from the lungs) is performed, the presence of other pathogens can influence the choice of antibiotic therapy. However, broad-spectrum antibiotics have not been proven to improve or worsen the patient’s outcome in cases of Hantavirus.
Influenza Pneumonia can be ruled in as a diagnosis if the Influenza polymerase chain reaction (PCR), a test that detects the influenza virus, comes back positive. This helps differentiate it from Hantavirus.
Viral Hemorrhagic Fevers are serious viral illnesses. Specific PCR tests are necessary to diagnose a single cause. The treatment for these fevers typically involves supportive care in an intensive care unit.
What to expect with Hantavirus Pulmonary Syndrome
Despite receiving high-level care in an intensive care unit, about one-third of patients may not survive the first 48 hours after they’re admitted. However, nearly half of the patients who are admitted with Hantavirus may not need a breathing machine (or mechanical ventilation) through intubation if they are properly managed with careful monitoring and appropriate fluids.
If patients start to get better in the first few days, there’s a good chance they could be taken off the breathing machine within the first week, and they often don’t have any major long-term complications. However, they might still experience subjective complaints like shortness of breath, tiredness, and muscle pain (myalgias).
Patients who have higher levels of antibodies that neutralize the immune complexes of the viral protein shell (nucleocapsid) have a higher chance of surviving the disease. These antibodies are the body’s defense mechanism to fight off the virus.