West Nile Virus and its effect on the kidney
By Christel Stokke, Kine Eggan, Anja Sveen
Contents
General Introduction
The West Nile Virus is a single-stranded RNA virus in the family Flaviviridae, genus Flavivirus, and is related to the pathogens responsible for dengue fever and yellow fever. The West Nile Virus was dicovered in Uganda in 1937, and has been responsible for thousands of cases of mortality and morbidity in humans, horses and birds. Epidemics were localized to Europe, Africa, the Middle East, and parts of Asia, and primarily caused a mild febrile illness in humans. In the late 1990`s the virus became more vicious and expanded its geographical range to North America. During the late summer of 1999, individuals where diagnosed in New York State, and in 2000, the epizootic expanded to 12 states. Today the West Nile Virus can be found in many avian and mosquito species throughout North America. Data shows that from 1999 to 2010, more than 2.5 million people were infected and there were more than 12,000 reported cases of encephalitis or meningitis and also more than 1,300 deaths
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Transmission cycle
WNV is transmitted by mosquitoes which are the prime vector, with birds, being the commonly infected animal and serving as a prime reservoir host. The mosquitoes become infected when they bite and feed on infected birds. One or two weeks later, the infected mosquito can transmit the virus to another animal or human. Usually the virus cycle is between mosquitos and birds, but there are a lot of incidental hosts, like humans and horses. However, humans, horses and other animals are ‘dead end’ hosts. This means that they do not develop high levels of the virus in their bloodstream, and therefore cannot pass the virus on to other biting mosquitoes. Some additional routes of human infection have also been documented, but in very small number of cases. Like transmission through blood transfusion, organ transplants, exposure in laboratory settings, breastfeeding and even during pregnancy from mother to baby. The WNV is not transmitted from person-to-person or from animal-to-person or from handling live or dead infected birds.
Symptoms in humans and horses
When infected with the West Nile Virus, signs of illness may not always be detected in people and animals. Approximately 80% of WNV infections in humans are subclinical and this is very similar to horses where most infections are asymptomatic. In humans, West Nile fever (WNF), which occurs in 20 percent of cases, is a febrile syndrome that causes flu-like symptoms, like fever, headaches, fatigue and muscle pain. Of all the people infected with West Nile Virus, 70-80% do not even develop any symptoms. Out of the symptoms that do appear, febrile illness is the most common one. Other symptoms that may occur is vomiting, diarrhea, headache, joint pains, body aches, or rash. Except weakness and fatigue, people infected with this type of WNV will in most cases recover completely. However there are some severe symptoms also. This includes a neurologic illness, such as encephalitis or meningitis. The illness can be known as West Nile encephalitis. This illness concerns the inflammation of the central nervous system, which is caused by the infection of the WNV. Less than 1 % of the people infected will get theses diseases. Signs of headache, neck stiffness, high fever, disorientation, coma, tremors, seizures or paralysis, can detect neurologic illness. Those people that are at greater risk for serious illness are the ones suffering from different types of medical conditions, such as diabetes, kidney diseases and hypertension. Unfortunately, some of the neurological effects may be permanent, but recovery after several weeks or months is possible. 10 percent of people suffering from neurological infection due to WNV will die.
In horse As mentioned before, the WNV does not always lead to symptoms of illness in animals or people. Horses however, seem to be more receptive to infection with the virus. In horses, as in human, the virus infects the central nervous system, through a neurological disease known as encephalitis. Primary symptom in the horse is loss of appetite and depression. In addition, several other symptoms such as fever, weakness and paralysis of hind limbs, ataxia, seizures, walking in circles or worst-case coma, may occur. Having these symptoms does not necessarily mean that the horse have West Nile encephalitis. Certain other diseases can cause a horse to show similar symptoms.
Treatment
Currently, patients infected with West Nile Virus have limited treatment options. Supportive care is the primary course of action. There is no FDA-licensed vaccine to fight the West Nile disease in humans, despite the research of many laboratories and institutions and vaccines available for use in horses.
Studies have suggested that ribavirin and interferon alfa-2b may be useful in the treatment of West Nile virus disease, but the efficacy of these agents has not been demonstrated in controlled clinical trials. An FDA-approved clinical trial has been launched to study the effectiveness of interferon alfa-2b in patients with West Nile encephalitis. To date, no controlled trials have studied the use of corticosteroids, anticonvulsants, or osmotic agents in the treatment of neurologic disease caused by West Nile virus.
Prevention
Prevention In humans, no vaccine is licensed for the prevention of WNV disease, although labarotury development is currently underway. Thus mosquito-control programs and personal protective measures are important in preventing WNV infection. In horse, on the other hand, specific vaccines are available. West Nile virus vaccines are produced either as an aid in prevention or reduction of viremia, encephalitis and clinical diseasea.
Global distribution
Phylogenetic studies have identified 2 main lineages of WNV strains. In the early 2000-s strains from lineage1 were present in Africa, India, and Australia and were reponsible for outbreaks in Europe, in the Mediterranean Basin, and in North America, whereas lineage 2 strains had been reported only in sub-Saharan Africa and Madagascar. The Hungarian equine WNV outbreak reported in 2008 was the first to be caused by a lineage 2 sub-Saharan strain in Europe. The pathogenicity of this lineage 2 strain resembled that of lineage 1 strains, and its sudden spread was unpredictable.
The WNV is found in Africa, Asia, Europe, and Australia, and has recently caused large epidemics in Romania, Russia, and Israel. The virus was recently introduced to North America, where it was first detected in 1999 during an epidemic of encephalitis in New York City. During 1999–2002, the virus extended its range throughout much of the eastern parts of the USA, and its range within the western hemisphere is expected to continue to expand. During 1999–2001, 142 cases of neuroinvasive WN viral disease of the central nervous system (including 18 fatalities), and seven cases of uncomplicated WN fever were reported in the USA.
Human: If we focus on the United States, no WNV cases had been reported prior to 1999. During the 1999 encephalitis outbreak, mentioned earlier, there were 62 diagnosed human cases and out of them seven deaths. • In 2000: 21 diagnosed human cases and two deaths. • In 2001: 66 diagnosed cases and nine deaths. • In 2002, 4161 diagnosed cases and 277 deaths across the United States • In 2003, 9175 human cases reported
Horse: • In 1999: approximately 25 horses became ill from infection with West Nile Virus. • In 2000: 60 documented clinical cases of infection. Approximately 60% of horses that actually showed signs of illness in 1999 and 2000 recovered from the infection. Others were euthanized or died as a result of infection. Many more horses were infected without showing any clinical symptoms of disease. • In 2001: 159 documented clinical cases of infection.
Kidney
Most important physiological functions of the Kidney The kidney is involved in maintenance of Homeostasis (isovolemia, isosmosis, isoionia, isohydria) Also storage of essential substances like water, electrolytes, glucose, and aminoacids It also participates in acid-base balance, cardiovascular regulation (especially through Angiotensin II synthesis) It takes part in elimination of exogenous and endogenous organic components (protein-metabolic endproducts, toxins, medicines.) Last but not least it is involved in hormone production (direct or indirect) 1-25-OH-D3; erythropoetin; PGE2; T3 (from T4 converted by kidney deiodase)
GFR and creatinine clearence
The volume of fluid filtered per minute from the glomerular capillaries into Bowman`s capsule is called the glomerular filtration rate (GFR). The GFR is the product of the net filtration pressure across the glomerular filter and the filtration coefficient (Kf)
GFR = Kf x net filtration pressure
The filtration coefficient (Kf) is the product of the fluid permeability of the glomerular filter and the area available for filtration. (Sjaastad, Hove, Strand, 2010)
Creatinine clearence Creatinine is a waste product that is produced continuously during normal breakdown of muscle tissue. As creatinine is produced, it is filtered from the blood through the kidneys and excreted in urine, and almost none of it is reabsorbed. The blood creatinine level is measured to test the kidney function. The kidneys' ability to handle creatinine is called the creatinine clearance rate, which helps to estimate the glomerular filtration rate (GFR) -- the rate of blood flow through the kidneys. The Glomerular Filtration Rate (GFR) is the rate of blood flow through the kidneys, it can´t be measured directly so that’s why we need to measure creatinine and creatinine clearance. The amount of blood the kidneys can make creatinine-free each minute is called the creatinine clearance. Creatinine clearance in a healthy young person is about 125 milliliters per minute -- meaning each minute, that person's kidneys clear 125 mL of blood free of creatinine. The GFR can vary depending on age, sex, and size. Generally, the creatinine clearance is a good estimation of the glomerular filtration rate. Testing the rate of creatinine clearance shows the kidneys' ability to filter the blood. As renal function declines, creatinine clearance also goes down. There are two main ways doctors use creatinine tests to measure kidney function: • Creatinine clearance can be precisely determined by measuring the amount of creatinine present in a sample of urine collected over 24 hours. This method requires a person to urinate exclusively in a plastic jug for one day, then bring it in for testing. Although the urine creatinine measurement method is inconvenient, it may be necessary to diagnose some kidney conditions. • GFR can be estimated using a single blood level of creatinine, which your doctor enters into a formula. Different formulas are available, which take into account age, sex, and sometimes weight and ethnicity. The higher the blood creatinine level, the lower the estimated GFR and creatinine clearance. For practical reasons, the blood test estimation method for GFR is used far more often than the 24-hour urine collection test for creatinine clearance. A low GFR or creatinine clearance demonstrates kidney disease. The decline in kidney function can be either acute (sudden, often reversible) or chronic (long-term and irreversible). Repeated GFR or creatinine clearance measurements over time can identify kidney disease as acute or chronic. Kidney function and creatinine clearance naturally decline with age. Fortunately, the kidneys have a huge reserve capacity. Most people can loose over half their renal function without symptoms or significant problems. Doctors determine the severity of chronic kidney disease with a staging system that uses GFR: Stage 1: GFR 90 or greater (normal kidney function) Stage 2: GFR 60-90 (mild decline in kidney function) Stage 3: GFR 30-59 (moderate decline in kidney function) Stage 4: GFR 15-29 (severe decline in kidney function) Stage 5: GFR less than 15 (kidney failure, usually requiring dialysis) People over age 60 may have an apparently normal creatinine blood level, but still have a low GFR and creatinine clearance. The 24-hour urine collection method, or one of the GFR estimation formulas, can more accurately identify the decline in kidney function. http://www.webmd.com/a-to-z-guides/creatinine-and-creatinine-clearance-blood-tests
Summary
List of references
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Weblinks
http://www.cdc.gov/westnile/transmission/ (CDC - centers for disease control and prevention)
http://www.westnile.state.pa.us/animals/horses.htm (Pennsylvania`s West Nile Virus Control Program)
http://www.ecdc.europa.eu/en/healthtopics/west_nile_fever/pages/index.aspx (European Centre for Disease Prevention and Control)
http://www.webmd.com/a-to-z-guides/creatinine-and-creatinine-clearance-blood-tests (WebMD)