What is Hemorrhagic Fever Renal Syndrome?
Hemorrhagic fever with renal syndrome (HFRS) is a disease that is spread through tiny particles in the air containing urine or feces of various small rodents like mice, rats, shrews, and voles. This disease is common in Asia and some parts of Europe and affects over 100,000 people a year. Different types of a virus, known as Orthohantavirus, can cause HFRS. These types most commonly include Hantaan, Dobrava, Seoul, and Puumala. Interestingly, these rodents don’t show any signs of being sick themselves, but they can still spread the virus.
Recently, due to a lot of new information about virus genes, the way these viruses are classified has been updated. This resulted in a new order called Bunyavirales and Hantavirus is now referred to as Hantaviridae. The viruses that cause HFRS fall under the Orthohantavirus group and Hantaviridae family.
Orthohantaviruses can lead to two main diseases: HFRS and Hantavirus cardiopulmonary syndrome (HCPS). Each disease is caused by different strains of the virus and has distinctly different symptoms. However, both diseases involve complications related to small blood vessels, uncontrolled blood clotting, and an overactive immune system. While HFRS is common in Asia and Eastern Europe, HCPS is more common in the Americas and tends to be more deadly.
HFRS is caused by inhaling the Hantavirus. Once inhaled, the virus spreads to other parts of the body through the immune system and particularly affects the blood vessels of the kidneys. Symptoms in patients with HFRS can vary from mild to severe, and in some cases can be fatal. So far there is no specific cure for Hantavirus infection, the treatment mainly includes supportive care to help relieve symptoms and improve the patient’s comfort.
What Causes Hemorrhagic Fever Renal Syndrome?
HFRS is a disease that occurs when someone breathes in Hantavirus. This virus primarily spreads through macrophages – a type of white blood cell that consumes harmful bacteria – and targets the blood vessels in the kidney. It’s worth noting that while many people living in areas where this virus is common show signs of having been exposed to the virus, most don’t show symptoms, suggesting that they either have no symptoms or only very minor ones.
Each type of this virus is linked with a specific type of rodent, and transmission from the rodent to humans usually happens when virus particles are aerosolized, or turned into a fine mist. The rodents that carry the virus don’t show any symptoms, and it’s extremely rare for the virus to spread from human to human. At least 24 types of Hantaviruses can cause sickness in humans but only a few types are most common. Hantaan and Dobreva viruses usually lead to more severe disease, Seoul virus is associated with moderate disease, and Puumala virus causes a milder form of HFRS known as nephropathia epidemica. This version is the most common in Europe and typically has less severe symptoms.
When it comes to understanding how HFRS impacts the body, there are three main things to consider:
1. The viral infection damages the inner layer of blood vessels causing increased leakage.
2. The infection also triggers the coagulation cascade, a series of events where your body forms a clot to stop bleeding.
3. A strong immune response is caused, leading to inflammation and damage to tissues.
Another important point to note is that the delayed symptoms in HFRS show that the immune response is of significant importance in understanding the disease study after symptoms start. There is also no cell death or toxic damage in the infected cells.
When the virus is in the lungs, it mainly targets the kidney. The outer layer of the kidney loses its function, leading to the presence of protein in the urine and a decreased rate of filtration in the kidney. There’s also damage to the tube that carries urine and inflammation. At the same time, activation of the clot formation causes a lack of platelets, the cells that help the blood clot, leading to bleeding.
Risk Factors and Frequency for Hemorrhagic Fever Renal Syndrome
The virus causing Hantavirus cardiopulmonary syndrome (HCPS), known as the Andes virus, usually spreads from rodents to humans. But there have been a few cases of human-to-human transmission. HFRS, a disease caused by this virus, is most common in Asia and Europe, with an estimated 60,000 to 150,000 cases reported globally each year.
China has the highest occurrence of this disease, accounting for about half of the cases worldwide. Russia comes in second, followed by Korea. Changes in climate impacting rodent populations can alter the spread of the disease each year. Depending on the region, more males can be affected, due to them spending more time outdoors. However, in Sweden, the disease frequency is equal among males and females.
A milder form of HFRS, known as nephropathia epidemica, is found in Scandinavian countries such as Finland, Sweden, Denmark, and Norway. The disease is present all year round and depends on how many rodents there are.
In Africa, the occurrences are low, but the virus has been found in other animals like shrews and bats. The types of this virus most commonly found in China are the Hantaan and Seoul viruses while in Europe, it’s Dobrava and Puumala.
Though the disease doesn’t typically cause serious illness, it can prove fatal in certain cases; up to 15% for HFRS depending on the viral strain. Things like smoking, age, and genetics can increase the severity of the disease, with most deaths occurring in patients over 70. Some genetic traits have been linked to higher death rates, which means differences in the immune system can significantly affect the outcome. Any exposure to rodents raises the risk of catching the disease.
Signs and Symptoms of Hemorrhagic Fever Renal Syndrome
Hemorrhagic fever with renal failure syndrome (HFRS) manifests as an illness with symptoms similar to the flu, including high fever, body aches, headache, backache, diarrhea, and vomiting. In some cases, patients can exhibit signs of hypotensive shock such as shortness of breath, confusion, excessive sweating, and rapid heart rate. Additional symptoms might be dizziness, chills, thirst, side pain, and tenderness in the rib area. The time between exposure and onset of symptoms is usually 12 to 16 days. This illness is often seen in people who have been exposed to rodents or have traveled to areas where the disease is common. In many cases, the disease progresses through 5 stages:
- Febrile: fever stage
- Hypotensive: low blood pressure stage
- Oliguric: reduced urine output stage
- Diuretic: increased urine output stage
- Convalescent: recovery stage
During each of these stages, the patient may display different signs. For instance, during the fever stage, patients can have flushing of the face, neck, and chest, subconjunctival hemorrhages (bleeding in the eye), slower than usual heart rate, acute kidney injury, and petechiae in the armpit and soft palate (small red spots caused by bleeding).
During the hypotensive or low blood pressure stage, which lasts up to two days, patients may experience symptoms like hypotension and a rapid heart rate, bleeding issues such as bruising, vomiting blood, nosebleeds, black stools, blood in the urine, and brain hemorrhage. Other symptoms can include sudden and severe abdominal pain due to paralytic ileus (a blockage of the intestines), and seizures.
The reduced urine output stage can last between three to seven days and is often associated with symptoms like low or no urine output, increased levels of waste products in the blood, abdominal or back pain, normal or high blood pressure, hemorrhages, and swelling in the peripheral and pulmonary regions.
The increased urine output stage can last from 2 to 3 weeks, during which the patient may produce several liters of urine per day, leading to symptoms like low blood pressure and signs of dehydration.
After this, the patient enters the recovery stage, which may continue for as long as 3-6 months. During this phase, the patient may experience fatigue and body aches, along with slowly resolving tubular concentrating defects.
Testing for Hemorrhagic Fever Renal Syndrome
Hemorrhagic Fever with Renal Syndrome (HFRS) can be detected using lab tests, scans, and other examinations. The following lab test results may point to HFRS:
- Increase in white blood cell count, decrease in platelet count, and high or normal level of red blood cells.
- Increased levels of liver enzymes, blood urea nitrogen, and serum creatinine, which indicate kidney damage or disease.
- Low sodium levels, high potassium, and phosphorus levels during the oliguric phase – a period of reduced urine production.
- Reduced levels of a particular part of the immune system, called complement (especially C3).
- Prolonged clotting and bleeding times, as shown by prothrombin, activated partial thromboplastin times.
- Increased presence of fibrin degradation products – these are products left over when blood clots are broken down.
- Urinalysis (urine test) showing blood and proteins in the urine.
- In cases where there is inflammation of the pancreas (pancreatitis), serum amylase and lipase levels will increase.
Low platelet count is a meaningful lab finding that’s tied to increased blood vessel permittivity (ability to allow liquids to pass through) and severity of the disease. At the beginning of Acute Kidney Injury (AKI), you might notice symptoms like less urine, protein in urine, and blood in urine. As the disease advances into the oliguric phase, you’ll see increased creatinine and decreased kidney function. No urine output can lead to imbalances of electrolytes (minerals that have an electric charge), such as high levels of potassium and phosphorus.
The immune response to the disease can provide clues about how it’s progressing. IgM antibodies are prevalent early in the disease and peak around 7 to 11 days after symptoms begin. Once recovery starts, IgM levels drop while IgG levels go up. Western blot (a lab method used to detect specific protein molecules) can also identify viral antigens (toxins or other foreign substances). PCR (a lab technique used to amplify DNA) is not as reliable because it increases the amount of virus in a short time.
Kidney ultrasounds, CT scans, and MRIs are often used to see the structure of the kidney. They can show kidney swelling, long-term changes, and the presence of blood resulting from bleeding inside the marrow of a bone – a possible consequence of HFRS.
Treatment Options for Hemorrhagic Fever Renal Syndrome
Treating a severe illness like hemorrhagic fever with kidney failure syndrome (HFRS) requires different approaches based on how serious the disease is and the patient’s general health. The most important part of managing HFRS is ensuring the patient’s blood circulation is functioning well. To achieve this, fluids are often given at an early stage, which is the main form of management for this disease. Generally, most patients will get better with appropriate care. In severe cases, a protein solution called albumin and other medications to stabilize blood pressure can be given through an IV line. It’s important to keep a close eye on the fluids given to the patient as they can cause leakage from the blood vessels. This is very likely during the stages of the disease where the patient has a fever or low blood pressure. Too much fluid can also cause fluid accumulation in the lungs when the kidneys are not able to produce urine properly.
Medications to promote urination, called diuretics, can be helpful if the patient’s body is retaining too much fluid and the kidneys are not producing much urine. However, if these medications are not enough, a treatment called renal replacement therapy may be necessary. This mainly applies to patients who have too much fluid in the body, issues with maintaining the body’s pH balance, and high levels of potassium in the blood.
Some studies have shown that certain antiviral medications, like ribavirin, can decrease the amount of virus in the body when used early in the disease by preventing the virus from reproducing. Yet, these antivirals have not shown effectiveness in later stages of the illness. Other studies suggest Icatibant, a drug that inhibits a substance called bradykinin, can help those with a specific type of infection (Puumala). Bradykinin influences the leakiness of blood vessels.
Theoretically, medications called corticosteroids should help with HFRS because a lot of the body damage comes from an overactive immune response. However, there’s still no clear evidence from large-scale trials to support their wide use. Therefore, they are used on a patient-by-patient basis.
Prevention is key to reducing the risk and death rate from hantavirus, which causes HFRS. Public health actions like preventing rodents from getting into houses and proper cleaning of rodent urine and feces are necessary to prevent outbreaks. It’s important that the cleaning of rodent urine and feces is done with the right gear and ventilation to avoid exposure to the virus. Often, officials keep track of rodent populations as part of this prevention strategy.
Currently, there aren’t any vaccines for hantaviruses approved by major health organizations like the FDA or WHO. However, vaccines made from inactivated viruses have been used in China and Korea and they seem safe and effective, though large scale studies are lacking. Vaccines made from parts of the virus’ DNA or some of its proteins are also being looked into. Early production of neutralizing antibodies, proteins that can bind to and neutralize the virus, is thought to be key in resisting infection, making this a crucial area of study. In fact, plasma (the clear part of the blood) from patients who have recovered from HFRS, which contains these neutralizing antibodies, has shown effectiveness when given in the early stages of the disease.
What else can Hemorrhagic Fever Renal Syndrome be?
When a patient in an area known for specific illnesses comes in with sudden kidney failure, doctors should consider the possibility of Hemorrhagic Fever with Renal Failure Syndrome. However, other illnesses can have similar symptoms, so they should also be taken into account. These include:
- Yellow Fever
- Ebola
- Dengue
- Leptospirosis
- Malaria
- Murine Typhus
- Sepsis (a severe infection in the bloodstream)
- Disseminated Intravascular Coagulation (a condition causing blood clots throughout the body)
- Thrombotic Thrombocytopenic Purpura (a disorder causing blood clots in small blood vessels)
What to expect with Hemorrhagic Fever Renal Syndrome
Usually, HFRS, a type of virus, will improve on its own and the patient will fully recover; however, the outlook varies depending on the specific type of HFRS virus the patient contracts. The overall chance of dying from HFRS is very low, but can vary between 0.43% and 15% based on the specific strain of the virus.
For example, the Puumala strain of the virus has less than a 1% mortality rate, meaning it rarely results in death. The Seoul virus often results in a moderate illness for the patient, whereas the Dobrava and Hantaan strains can lead to more severe illness, with a 5-15% chance of death.
Regardless of the strain, all types of HFRS can cause a range of symptoms, from none at all to severe illness. But with recovery, kidney functions usually revert to what they were prior to the illness.
Possible Complications When Diagnosed with Hemorrhagic Fever Renal Syndrome
Hemorrhagic fever with renal failure syndrome is a serious condition that can lead to death due to failure of many organs in the body. The complications that could arise from this condition are:
- Acute encephalomyelitis – a sudden inflammation of the brain and spinal cord
- Pulmonary edema – a condition where fluid builds up in your lungs
- Coagulation abnormalities like disseminated intravascular coagulation – a condition that causes blood clots to form throughout the body’s small blood vessels
- Acute respiratory distress syndrome – a severe lung condition causing shortness of breath
- Multiorgan failure – when several organs fail to function normally
- End-stage renal disease – a severe long-term condition where the kidneys stop working properly
- Acute pancreatitis – a sudden inflammation of the pancreas
Preventing Hemorrhagic Fever Renal Syndrome
It’s vital for patients to understand the risks associated with coming into contact with rodent urine and feces. This risk is especially high for those who live in or travel to areas where these rodents are common, or for individuals who work in jobs like farming, forestry, or the military. It’s important for patients in these situations to be aware and educated in order to limit their contact with rodents as much as possible.
For patients undergoing the first phase (known as the oliguric stage) of a certain disease, a diet low in sodium and limiting their fluid intake is often advised. Then, during the second phase (the diuretic stage), they are encouraged to up their fluid intake. During the initial, acute phase of the disease, rest in bed is generally recommended. All these measures are aimed at helping manage the disease effectively.