Overview
Hantavirus is a naturally occurring acute infectious disease caused by rodents, characterized by fever, hemorrhage, congestion, hypotensive shock, and renal damage. Hantavirus infection is caused by the direct action of the virus and an immunopathological response, with antiviral drugs available for the febrile period, and pharmacological and surgical treatments available.
Definition
Epidemic hemorrhagic fever, also known as renal syndrome hemorrhagic fever, is a natural epidemic caused by the epidemic hemorrhagic fever virus (hantavirus), with rodents as the main source of infection, and is an important infectious disease that endangers human health.
Fever, hemorrhage, congestion, hypotensive shock and renal damage are the main clinical manifestations.
Stages
Typical cases have 5 stages: fever stage, hypotensive stage, oliguria stage, polyuria stage and recovery stage.
In severe patients, the hypotensive and oliguric phases can overlap.
Mildly ill patients may go beyond the stage, i.e., directly from the febrile stage to the recovery stage.
Morbidity
Epidemiology
Hantavirus is a worldwide epidemic, and is currently distributed in 78 countries on 6 continents.
Since the 1980s, the intensity of the epidemic has increased, and the annual number of reported cases nationwide has exceeded 100,000, which is a serious danger and has been listed as one of the key infectious diseases to be prevented and treated in China.
The disease is widely prevalent in China, and so far more than 20 provinces, cities and districts have reported the occurrence of the disease. In recent years, the epidemic has been significantly controlled.
Causes
Causes
Hantavirus infection, leading to damage to the function and structure of infected cells.
Source of infection: mainly rodents.
Route of transmission: still unknown, may be contact, respiratory, digestive tract, vertical transmission.
Susceptibility: The population is generally susceptible.
Pathogenesis
Inflammatory mechanism
Immunity: After the virus invades the human body, it can cause a series of immune responses, causing tissue damage.
Type I, II, III and IV allergic reactions and various cytokines and mediators (e.g., IL-1, TNF) can play a role in the pathogenesis of the disease, but type III allergic reactions are the main cause of vascular and renal damage in this disease.
Mechanisms by which hemorrhage, shock and acute renal failure occur
Shock: It is divided into primary shock and secondary shock, which occurs in the course of the disease from 3 to 7 days. Primary shock is associated with extensive damage to small blood vessels throughout the body, increased permeability of the vascular wall, and decreased effective blood volume due to massive plasma extravasation.
Bleeding: is associated with the following factors.
Vascular wall damage leading to extravasation of red blood cells.
Coagulation dysfunction due to disseminated intravascular coagulation.
Thrombocytopenia and dysfunction.
Increased heparin-like substances.
Acute Renal Failure: associated with inadequate tissue perfusion and damage to the renal parenchyma due to the following.
Decreased renal blood flow.
Glomerular and tubular lesions due to immune complex deposition.
Ischemic necrosis of glomeruli due to blood stasis.
Increased secretion of renin and angiotensin.
Renal tubules are blocked by protein.
Renal interstitial edema and hemorrhage.
Symptoms
Incubation period 4 to 6 days, usually 7 to 14 days.
Fever period
Initial stage
Typical symptoms include chills, chills and high fever.
The febrile period usually lasts for 4 to 6 days, and less frequently for more than 10 days. The body temperature is 38 to 40℃, and the temperature may fluctuate greatly, or remain high all the time.
Usually, the higher the fever, the more serious the condition is, and the more chances of hypotensive shock and oliguria occur.
Most patients have obvious gastrointestinal symptoms, manifested as loss of appetite, and in severe cases, gastrointestinal symptoms such as nausea, vomiting and eructation.
A few patients may also have neuropsychiatric symptoms such as excitement, delirium, restlessness and drowsiness, and a very small number of critically ill patients may have convulsions, coma and signs of meningeal irritation (including headache, vomiting, cervical rigidity, etc.).
Some patients with headache, lumbago, orbital pain (triple pain) and generalized limb joint pain, abdominal pain, diarrhea, abdominal pain, abdominal muscle tension, abdominal pressure and rebound pain can be seen in severe abdominal pain.
The 2nd to 3rd disease day
Half of the patients have significant congestion and flushing of the conjunctiva of the eyeballs and the skin of the face, neck and upper chest (triple red), which resembles the appearance of drunkenness.
Mucosal hemorrhage is most common in the soft palate, uvula and posterior pharyngeal wall, manifested as reticular, punctate or hemorrhagic spots, tonsils are not enlarged.
Skin hemorrhage occurs bilaterally in axillae and anterior chest and back of shoulder, mostly as bleeding spots or scratch-like, streak-like bleeding spots, and ecchymosis is often seen at the site of pinprick.
Early bundle arm test may show positive.
In severe cases, there are nosebleeds, hemoptysis, vomiting blood, blood in the stool and hematuria.
Punctate or patchy hemorrhage can be seen in the conjunctiva of the eye, and edema is mostly seen in the conjunctiva of the eye, which is a characteristic manifestation in the early stage.
In mild cases, ripples or folds of the conjunctiva can be seen when the eyeball is rotated or the examiner squeezes the upper and lower eyelids with his hand.
Moderate edema has a blister-like bulge in the bulbar conjunctiva that clearly protrudes above the plane of the cornea.
Severe edema is a bulging bulbous conjunctiva that is jelly-like or fresh lychee flesh-like, protruding from the plane of the eye fissure.
Moderate to severe bulbar conjunctival edema is often associated with eyelid and facial edema, and even ascites, pleural effusion, and pericardial effusion.
Globe conjunctival edema is of diagnostic importance and suggests severe capillary and small vessel damage, significant plasma leakage, and a greater likelihood of hypotensive shock.
2nd to 4th disease day
Renal damage may occur during the febrile period, manifested by proteinuria, hematuria, and a tendency to oliguria.
Some patients have jaundice, hepatosplenomegaly and abnormal liver function.
Hypotensive shock period
After 4 to 6 days of fever, the body temperature slowly subsides or suddenly recedes, but other symptoms worsen, and some patients develop hypotension or shock.
The duration ranges from several hours to several days.
Decrease in blood pressure with increased heart rate and pulse rate is categorized into hypotensive tendency, hypotension and shock.
Hypotensive tendency: systolic blood pressure 90 to 100 mm Hg.
Hypotension: systolic blood pressure 60 to 90 mm Hg.
Shock: systolic blood pressure <60 mm Hg.
Pallor or cyanosis (blue) of face and lips, cold extremities, florid skin.
Impaired consciousness, initially agitation, followed by delirium, somnolence, lethargy, and coma.
Oliguria or anuria.
Decreased central venous pressure (CVP), <6 mm Hg.
Oliguria stage
Oliguria or anuria is the most prominent manifestation of acute renal failure in this disease.
Acute renal failure is often accompanied by varying degrees of uremia, acidosis, water intoxication and water-electrolyte imbalance.
Clinical anorexia, nausea, vomiting, abdominal distension, dry mouth, often with intractable eructation.
Facial and lower extremity edema, some patients may be accompanied by pulmonary edema, pleural effusion and ascites.
Blood urea nitrogen and creatinine are mostly significantly elevated.
Nephroencephalopathy with dizziness, headache, drowsiness, irritability, delirium, convulsions and coma.
Hypervolemic syndrome with distended face, engorged and angry body veins, pulse flooding, increased blood pressure, increased pulse pressure, and hyperacusis.
Metabolic acidosis.
Polyuric phase
As the recovery of tubular reabsorption function is later than the repair of glomerular filtration function, the urine volume gradually increases into the polyuric phase after the oliguric phase. The clinical significance of the increase in urine volume varies according to the mode of increase.
Sudden increase: the urine volume suddenly increases to more than 1500 ml in 24 hours, good response to diuretics, mostly mild, good prognosis.
Gradual increase: urine output increases gradually, with an average increase of 200-500 ml per day, this type is more common in clinical practice and has a better prognosis.
Stagnant: urine output increases to 500-1000 ml in 24 hours and no longer increases, sometimes it needs to be induced by diuretics before there is a small increase, this situation suggests that renal impairment is more serious, and we should be vigilant about the occurrence of chronic renal failure or non-oliguric renal failure.
Various clinical manifestations of oliguria can still be continued in the early stage of polyuria, especially nutritional imbalance, electrolyte disorders, serious infections and bleeding.
If large amount of urination is not supplemented with water and electrolytes in time, dehydration, hypokalemia and hyponatremia are very likely to occur, and even secondary shock (water loss shock) and secondary renal failure may occur, which may endanger the patient’s life in severe cases.
Recovery period
Most patients start to recover in the third to fourth week after the disease. Generally, the recovery period is marked by the decrease of urine output to about 2000 ml per day and the decrease of urea nitrogen and creatinine to normal.
In a few severely ill patients, the recovery time is longer, taking 1 to 3 months or more. Individuals may evolve into chronic renal failure.
House mouse hemorrhagic fever clinical manifestations are milder, the five stages of the passage of the incomplete, while the complications are few, the case fatality rate is mostly less than 1%.
Performance of special populations
Pediatric hemorrhagic fever
The onset of the disease is mostly acute, the heat pattern is irregular, and the degree of heat is high.
Systemic toxic symptoms are mild, and there may be meningeal irritation.
Digestive tract symptoms are obvious.
Lack of typical “three red”, headache, abdominal pain as the main manifestation.
Less hemorrhagic tendency and hypotensive shock, mild renal damage.
The death rate is low.
Elderly hemorrhagic fever
Clinical manifestations are atypical, and there are many patients with low to moderate fever, while a few patients have no obvious fever.
Hypotensive shock occurs early with high incidence.
Kidney damage is serious, with high incidence of oliguria and urinary closure.
Gastrointestinal hemorrhage, cerebral hemorrhage, pulmonary edema, pulmonary infection and central nervous system complications are often combined.
There are many severe and critical cases with high mortality rate.
Consultation
Department of Medicine
Infection Department
If you have a history of close contact with patients with epidemic hemorrhagic fever, have been to an infected area recently, and have chills, high fever, headache, backache, orbital pain, and significant congestion and flushing of the skin of the face, neck, and upper chest, it is recommended that you consult a doctor promptly.
Emergency Department
Immediate consultation is recommended when there is high fever that does not go away, vomiting of blood, little or no urine, cyanosis, irritability or drowsiness, or coma.
Preparation for medical treatment
Preparation for consultation: registration, preparation of information, common problems
Tips for seeking medical treatment
A general physical examination, electrocardiogram, renal ultrasound, chest X-ray or chest CT may be required. Wear loose-fitting clothes and avoid wearing clothes made of metal. Those who are pregnant or planning to become pregnant should inform the doctor in advance.
For patients with high fever, physical cooling can be done first, such as applying cold compresses to the forehead, as well as wiping hands, feet and armpits with warm water.
Preparation Checklist for Medical Consultation
Symptom Checklist
Especially focus on the time of onset of symptoms, special manifestations, etc.
Is there fever and chills? What is the highest degree?
Is there headache, back pain, orbital pain?
Is there flushing of the face, neck and chest, bleeding from the mucous membranes?
Is there a decrease in urine output? How much do you urinate a day?
Are there any skin rashes or other abnormalities?
How long have these symptoms been present?
Medical History Checklist
Has there been close contact with a person with epidemic hemorrhagic fever at any time? Has there been a visit to an epidemic hemorrhagic fever infected area?
Has there been recent contact with rodents?
Have you eaten unclean food?
Is there an autoimmune deficiency disease? or immunocompromised?
Checklist
Test results for the past 6 months, which can be brought to the doctor’s office
Laboratory Tests: blood test, urine test, blood biochemistry test
Electrophysiology and imaging tests: electrocardiogram, renal ultrasound, chest X-ray or chest CT examination
Medication List
Medication used in the last 3 months, bring the box or package with you if available
Antiviral: ribavirin
Diuretics: Furosemide
Others: low molecular dextrose, hydrocortisone
Diagnosis
Diagnosis is based on
Epidemiologic history
History of field work in an infected area and overnight stay during the epidemic season, within 2 months prior to the onset of the disease.
History of direct or indirect contact with host animals such as rodents or their feces.
History of eating rodent-contaminated food that has not been adequately heated.
Clinical manifestations
Short-term fever and “three pains” as the main symptoms of infection.
Signs of congestion (triple red), oozing and hemorrhage, and renal damage.
Typical patients should have five stages: fever, hypotension (shock), oliguria, polyuria and recovery.
Atypical patients should pay attention to the presence or absence of polyuria (urine output >3000 ml per day).
The disease is characterized by severe fever and severe illness.
Laboratory tests
Routine blood tests: there are “three highs and one low”, i.e. increased peripheral blood white blood cell count (WBC), increased ratio of heterogeneous lymphocytes, increased hemoglobin and decreased platelet count.
Urine protein: usually above “2+”.
Serum antibodies: anti-hantavirus IgM positivity or double blood anti-hantavirus IgG positivity with more than 4-fold increase in potency.
Pathogenetic testing: within 15 days of the onset of the disease, the application of RT-PCR to detect positive serum pathogenic hantavirus RNA is of great diagnostic value.
Differential diagnosis
Fever should be differentiated from the following diseases
Influenza
Most of them have a history of cold or influenza epidemic, upper respiratory tract symptoms are more prominent, and the systemic disease improves significantly with the fever subsiding, and there are few other positive signs.
Influenza
Most popular in winter and spring, common in children, with meningitis-specific symptoms and signs, such as headache, obvious or projectile vomiting, and meningeal irritation such as cervical rigidity.
Skin petechiae are mainly on the lower body, blood picture shows bacterial infection phase, and cerebrospinal fluid shows purulent meningitis.
Fever with headache is the most prominent, the natural course of fever is more than 2 weeks, there may be transient hypotension, but there are no signs of exudation.
Typhus
Rash on the 5th day of fever, may have a hemorrhagic rash with more congestive rash and a larger number of rashes.
Renal damage is mild with only transient proteinuria.
The diagnosis can be confirmed by an exophthalmos reaction (OX19) with a potency of 1:160 or more, or by a fourfold increase in double serum potency.
Detection of typhus anti-hantavirus IgM antibodies is negative.
Typhoid fever
Fever is prolonged.
There is mostly no hypotension, and bleeding and changes in urine output are rare.
Symptoms of poisoning are characterized by pallor, apathy and relatively slow pulse.
Peripheral blood leukocytes are normal or decreased, especially eosinophils, and platelet count is usually normal.
The diagnosis is confirmed by culture of blood, feces or bone marrow for S. typhi.
Leptospirosis
Most commonly occurs in summer and fall.
History of exposure to infected water, high fever, malaise, accompanied by gastrocnemius muscle tenderness and generalized lymph node enlargement, heterogeneous lymphocytes are rare.
Positive blood culture can confirm the diagnosis.
Septicemia
There is often a primary lesion.
There are chills and high fever with severe systemic toxicity, but no signs of exudation.
Blood picture shows bacterial infection phase.
Heterogeneous lymphocytes are rare.
Platelets are mostly unremarkable.
Positive blood cultures confirm the diagnosis.
Hypotensive shock phase should be differentiated from the following diseases
Acute toxic bacillary dysentery
The disease occurs in summer and fall, and is most common in children with a history of unclean eating. The onset of the disease is acute, characterized by high fever, chills, depression or convulsions, and toxic shock, respiratory failure or coma may occur rapidly.
Fecal specimens collected by anal finger or diagnostic enema are helpful for diagnosis.
Shock type pneumonia
Most of them have a history of cold exposure, and have respiratory symptoms such as cough, sputum, chest pain and shortness of breath at the beginning of the disease.
Hypotensive shock occurs on the second to third day of illness.
No obvious signs of exudation.
There is no increase in lymphocytes, thrombocytopenia and severe proteinuria.
X-ray chest radiography is helpful in confirming the diagnosis.
Differentiation of severe bleeding tendency
Differentiate from acute leukemia, anaphylactic and thrombocytopenic purpura.
Differentiation of renal injury
Differentiate from renal diseases such as primary acute glomerulonephritis, acute pyelonephritis and nephropathy.
Treatment
Principles of treatment
Early detection, early rest, early treatment and local isolation treatment.
Report as Class B infectious disease.
Closely observe the vital signs and provide appropriate comprehensive treatment for the clinical conditions of the five stages.
Physical cooling or adrenocorticotropic hormone can be used during the fever stage.
When hypotensive shock occurs, blood volume should be supplemented, commonly used are low molecular dextrose, balanced saline and glucose saline, plasma, protein and so on.
In case of oliguria, diuretics (e.g. furosemide, etc.) can be administered intravenously.
Polyuria should be supplemented with adequate fluids and electrolytes (potassium salts), mainly taken orally.
After entering the recovery period, attention should be paid to preventing complications, strengthening nutrition and gradually resuming activities.
[Special Reminder] All medications should be used under the guidance of a professional doctor, and should not be adjusted or stopped on their own.
Medication
Low molecular dextrose
For decreased blood volume with protein deficiency.
Intravenous drip.
Adverse reactions such as skin itching, nausea, vomiting and asthma may occur in a few cases.
Hydrocortisone
Intravenous drip.
May relieve inflammatory response.
Furosemide.
Indicated for edema due to renal disease and may relieve dysuria.
Common adverse reactions are water and electrolyte disturbances, which can cause thirst, fatigue, and muscle aches.
Potassium Chloride
Indicated for hypokalemia of various causes and is used here for electrolyte replacement.
Common adverse reactions include gastrointestinal irritation such as nausea, vomiting and throat discomfort.
Symptomatic treatment and treatment of complications
Those with significant bleeding should be transfused with fresh blood to provide large amounts of normally functioning platelets and clotting factors.
Those with markedly reduced platelet counts should be transfused with platelets.
For pulmonary edema, stop the infusion and apply cardiotonic and vasodilator drugs.
For those with impaired liver function, hepatoprotective therapy can be given.
In severe cases, antibiotics can be applied to prevent infection as appropriate.
Treatment of fever
The main treatments during the febrile period include antiviral, reducing exudation and alleviating bleeding. Prevent hypotensive shock and renal failure.
Antiviral
Antiviral drugs are available as ribavirin.
Common adverse effects include anemia and malaise, which disappear when the drug is stopped.
Reduce exudation and bleeding
Large doses of vitamin C can be used to reduce capillary permeability, accelerate blood clotting and stimulate coagulation. Occasionally, patients may have adverse reactions such as urate and oxalate stones, which should be taken in accordance with medical advice.
Prevention of oliguria
In the late stage of fever, when the daily urine output is less than 1000 ml or the average urine output per hour is less than 40 ml, diuretics and renal vasodilators can be applied as appropriate on the basis of replenishing blood volume.
Treatment of Hypotensive Shock
The treatment of hypotensive shock is mainly to actively replenish blood volume, and carry out corresponding treatment for microcirculatory dysfunction, acidosis, cardiac insufficiency and so on. Strive for the blood pressure to rise as soon as possible and maintain stability. Supplementation of blood volume should be early, rapid and appropriate.
Supplementation of blood volume
Fluid components
Balanced salt solution and low molecular dextrose anhydride solution are the main components.
Serious patients should apply colloidal solutions such as plasma or human albumin.
Early, rapid and moderate volume expansion
Adjustment of acid-base balance, with acidosis, the use of 5% sodium bicarbonate solution, the dose of drugs as prescribed by the doctor.
Other
The application of vasoactive drugs after rapid rehydration and cardiotonic, acid correction and other treatments, blood pressure recovery is still unsatisfactory, discretionary use of vasoactive drugs, such as mesoglobin, dopamine, etc.; according to the actual situation.
In case of hypercoagulation and fibrinolysis, anticoagulation therapy is appropriate.
Treatment of oliguria
In order to facilitate early treatment, when the hourly urine output is less than 30 milliliters, it is necessary to take appropriate therapeutic measures in time.
The principle of treatment in this period is to stabilize the internal environment of the body, promote the recovery of renal function and prevent complications.
Stabilization of internal environment
Water and electrolyte balance
Electrolyte solution can be supplemented 500-1000 ml per day, and diuretics should be applied at the same time to keep the urine output above 50 ml/hour.
Fluid volume should be limited, i.e., intake = output + 500 ml of fluid.
Nutritional supportive therapy
The amount of sugar should not be less than 200 grams per day, and high quality protein should be supplemented.
Maintain acid-base balance
Give discretionary correction according to acid-base situation. 5% sodium bicarbonate is commonly used.
Maintain the stability of blood pressure and plasma osmolality.
When plasma colloid osmolality decreases, use human albumin or plasma.
Promote diuresis
Highly effective diuretics: furosemide, etanercept, bumetanide, etc.
Diarrhea therapy
Mannitol, magnesium sulfate, and the Chinese herb rhubarb can be used.
Dialysis methods
It can be done by hemodialysis, rectal dialysis or peritoneal dialysis.
At present, hemodialysis is the most commonly used in hospitals.
Hemodialysis is faster and more effective than peritoneal dialysis. It can transmit urea nitrogen in a short period of time, which can rapidly improve uremia.
Peritoneal dialysis should strictly implement the disinfection and isolation system during operation to prevent secondary infection and keep the pipeline open.
Albumin and plasma should be appropriately supplemented during dialysis to prevent the occurrence of hypoproteinemia.
Treatment of polyuria stage
Migration stage and early polyuria are treated according to the principles of oliguria stage. After the polyuria stage according to the treatment principles of this stage: regulate water and electrolyte balance, strengthen supportive therapy.
Supplementation of the appropriate amount of fluid rehydration in principle without restriction, but should not enter too much.
Maintain access and electrolyte balance. Rehydration is mainly oral, and intravenous rehydration is available for those with poor appetite.
Supportive therapy patients should eat nutritious, easy to digest, high potassium content of the diet, such as egg custard, milk, cornmeal, spinach puree and so on.
For those with severe anemia and hypoproteinemia, fresh blood, plasma, or human albumin can be imported as appropriate.
When the urine volume exceeds 3000 ml/day, potassium should be supplemented mainly orally, and attention should be paid to the supplementation of electrolytes such as sodium and calcium.
Prevent secondary infection.
Treatment during the recovery period
Continue to pay attention to rest and gradually increase activity. After discharge from the hospital, rest can be taken for 1~3 months according to the condition of recovery, which can be prolonged appropriately in heavy cases.
Strengthen nutrition, give high sugar (no diabetes mellitus), high protein, multi-vitamin diet.
It can be appropriate to drink brown sugar water and intake of adequate amount of rice, steamed bread and other staple foods.
Eat more milk, egg whites, soy products and other foods rich in high quality protein.
Moderate consumption of spinach, celery, bananas, grapes and other vitamin-rich fruits and vegetables.
Complications
Treatment of hemorrhage should be directed at the cause of bleeding, and transfusion of fresh blood is the main measure to treat bleeding.
For gastrointestinal bleeding, bacitracin can be given orally by drip or diluted thrombin, and norepinephrine can also be given orally by diluted norepinephrine.
If there is secondary hyperfibrinolysis, 6-aminohexanoic acid or p-carboxybenzylamine can be used. If the blood heparin-like substance is increased, fish essence protein can be considered.
Patients with renal failure may be treated with hemodialysis to improve renal function and promote disease recovery.
Central nervous system complications cerebral edema, cerebral hemorrhage caused by intracranial hypertension, given mannitol dehydration.
Those who develop convulsions can be sedated with diazepam or barbiturate.
Spontaneous renal rupture is surgically sutured.
Prognosis
Cure
The case fatality rate remains high in patients with severe forms of the disease. The main causes of death are shock, uremia, pulmonary edema, and hemorrhage (mainly cerebral and pulmonary hemorrhage, etc.).
In recent years, due to improved treatment measures, the number of deaths due to shock, uremia, and pulmonary edema has been gradually decreasing, while the number of deaths due to hemorrhage is relatively high.
Prognostic factors
The prognosis of hemorrhagic fever is related to the type of virus infection, the severity of the disease, the timing of treatment, and the appropriateness of measures.
With the improvement of early diagnosis and treatment measures, the case fatality rate has been reduced from 10% to 3%~5%.
Daily life
Daily life
Isolate in situ and treat as soon as possible.
Replenish adequate fluids and electrolytes (potassium salts), mainly by mouth.
Eat a nutritious, easily digestible diet high in potassium, such as egg custard, milk, cornmeal, and spinach puree.
Enhance nutrition by giving a high-sugar (for those without diabetes), high-protein, multivitamin diet.
It can be appropriate to drink brown sugar water and intake of adequate amount of rice, steamed bread and other staple foods.
Eat more milk, egg whites, soy products and other foods rich in high quality protein.
Moderate consumption of spinach, celery, bananas, grapes and other vitamin-rich fruits and vegetables.
Prevention
When the affected area is identified as an infected area, vigorous efforts should be made to exterminate rats and mice.
Keep the living environment clean and tidy, and regularly tidy up the environment.
Eliminate rodent habitats and breeding places, especially kitchens, dormitories and warehouses.
Prevent rats from invading and contaminating food.
If necessary, we can unify the drug poisoning to reduce the density of rats.
Do not touch rodents and their excreta directly with your hands.