leptospirosis



Overview

Pathogenic leptospirosis is an acute infectious disease characterized by fever, malaise, muscle aches, and enlarged lymph nodes. Antimicrobial therapy is the mainstay of treatment, supplemented by general symptomatic treatment. Most patients can be cured, but the prognosis for heavy patients is poor, and can be fatal.

Definition

Leptospirosis (leptospirosis), referred to as leptospirosis, is an acute infectious disease caused by pathogenic leptospirosis (leptospirosis) [1].

It belongs to category B infectious diseases stipulated in China’s law on the prevention and control of infectious diseases [2].

Leptospira can be divided into two categories: pathogenic and non-pathogenic. Only pathogenic leptospirosis infection caused is called leptospirosis [3].

Typical clinical manifestations in the early stages are three major symptoms (chills, fever, aches and pains, and generalized malaise), and three major signs (redness of the eyes, leg pains, and enlarged lymph nodes).

Classification

Leptospirosis Pathogenesis

Leptospirosis has been identified globally in 23 groups and 223 types, but the main ones confirmed in China are 18 groups and 70 types.

In China’s leptospirosis epidemics, leptospirosis infections caused by paddy fields are dominated by the jaundiced hemorrhagic group; leptospirosis infections caused by rainwater and flooding are mostly caused by the Pomona group.

Main types of epidemics

Leptospirosis is mainly categorized into paddy, rainwater, and flood types depending on the area of infection [1].

Main flora

Jaundice hemorrhagic group

Pomona group

Pomona group

Transmission factors rodent urine contamination storm water flooding inundation

Transmission factors

Rodent urine contamination

Storm water

Flood inundation

Infected areas paddy fields, ponds low-lying villages flooded areas

Infected areas

Paddy fields, water ponds

Low-lying villages

Floodplain

Incidence is more concentrated and scattered more concentrated

Incidence

More concentrated

Dispersed

More concentrated

Domestic region Southern rice cultivation area North and South North and South

Domestic region

Southern rice cultivation zone

North and South

North and South

Morbidity

Global

Leptospirosis is considered to be the most widely distributed zoonosis in the world, mainly in tropical and subtropical regions.

The disease has a high rate of underreporting and no reliable global incidence data are available. It is estimated that there are more than one million cases worldwide each year, including about 60,000 deaths [4-5].

Domestic

It is disseminated or endemic in the vast majority of the country.

The onset of the disease is concentrated in the rainy and warm summer and fall seasons, and short-term epidemics can occur after the occurrence of heavy rainfall.

Infected people are mainly young adults, and there are more males than females.

With global warming, climate disasters and increased international travel, the incidence of leptospirosis has increased in China, and in 2021, the number of cases of leptospirosis in the country was 403 cases, with an incidence rate of 0.03/100,000, and 2 deaths [2].

Etiology

Causes of the disease

There are three factors that contribute to the prevalence of leptospirosis.

Source of infection

The blood and urine of animals infected with leptospirosis, such as rats, pigs and dogs, as well as the water and soil contaminated by them, are the main sources of infection.

In recent years, rodent-borne leptospirosis has been decreasing in China, and it is mainly transmitted by livestock such as pigs and dogs [1].

It should be noted that patients with leptospirosis are not the source of infection of leptospirosis.

Transmission

Transmission is mostly through direct contact.

Leptospirosis can be excreted with the urine of infected animals to contaminate water and soil, and when in contact with the contaminated water and soil, it can invade the tiny breaks in the skin and cause infection.

Fishing in rivers, wading and swimming, as well as miners and sewerage workers who work in contact with sewage contaminated by diseased rats may also become infected and develop the disease.

When eating food and water contaminated by the hookworm, it can also invade the human body through the digestive tract.

Susceptible People

People are generally susceptible.

People engaged in field work or animal workers are more susceptible, such as farmers, fishermen, slaughter workers, veterinarians and military personnel, off-road riding and other groups [1,6].

Newcomers to the infected area are highly susceptible and have a higher proportion of severe disease after infection.

Pathogenesis

The pathogenesis of leptospirosis can be divided into three stages: early, middle and late.

In the early stage, leptospires enter the body and multiply rapidly, forming acute leptospirosis. After the early stage of the disease, there will be a period of remission, and it will also reoccur and enter the middle stage.

In the middle stage the leptospires enter the internal organs, damaging them to varying degrees and causing damage to several organs. The basis of the lesion is toxic damage to the systemic capillary infection.

Posterior fever, ocular or neurologic sequelae may occur in the later stages due to immunopathologic reactions [1].

Symptoms.

The clinical course of leptospirosis varies. Most patients can be asymptomatic, while severe cases are potentially fatal [7].

In general, the incubation period tends to be 7 to 14 days, with an average of 10 days.

Main symptoms

Based on clinical features, the disease can be divided into three stages and five types [1].

Early stage (leptospirosis stage)

Occurring within 3 days after the onset of the disease, it is mainly characterized by acute fever, with body temperature mostly around 39℃.

It may be accompanied by chills and chills, and there may be headache, generalized muscle pain, superficial lymph node enlargement, conjunctival congestion, and bilateral posterior calf gastrocnemius muscle tenderness.

Middle stage (organ damage stage)

In 3 to 10 days after the onset of the disease, there can be obvious organ damage, which is mainly categorized into the following five types.

Influenza typhoid type

Also known as the infected toxic type, the most common, the clinical manifestations are similar to influenza, there may be fever, malaise, muscle pain, conjunctival congestion and so on.

There may be superficial lymph node enlargement, mostly in the inguinal and axillary lymph nodes, the size of soybean to fava bean, with pressure pain, without suppuration.

Pulmonary hemorrhagic type

Includes common pulmonary hemorrhage type and diffuse pulmonary hemorrhage type.

Lung ordinary hemorrhage type: there may be cough, sputum with blood manifestation.

Diffuse pulmonary hemorrhage: also known as pulmonary hemorrhage, is more dangerous, may be manifested as hemoptysis, pale, irritable, a few patients may be manifested as a large amount of blood gushing out of the mouth and nose.

Jaundice hemorrhagic type

Also known as external ear disease, rare in China.

It is characterized by yellowing of skin, loss of appetite, nausea, vomiting, etc. In severe cases, hepatic encephalopathy, renal failure and even death may occur.

Kidney failure

The manifestations are foam in the urine, hematuria, decreased urine volume, which can be returned to normal.

Only a few serious cases may develop azotemia, oliguria or anuria, or even renal failure.

Meningoencephalitis type

It manifests as severe headache, irritability, vomiting, neck stiffness, drowsiness, convulsions and even coma, and cerebral edema, brain hernia and respiratory failure may occur in severe cases.

The condition is critical and the prognosis is poor.

Later stages (recovery or postdrome stage)

Often occurs 2 weeks to 6 months after the onset of the disease.

Post-onset fever

Manifests as a reoccurrence of fever after the fever has subsided, with a temperature around 38°C. The fever may subside on its own after 1 to 3 days and no treatment is required.

Reactive meningitis

Manifested by meningitis manifestations such as headache, irritability, neck stiffness, etc. during postictal fever, but the cerebrospinal fluid tests are normal and the prognosis is good.

Posterior ophthalmoplegia

Mainly iridocyclitis, choroiditis, and uveitis.

The eyes may have pain or photophobia without discharge, blurred vision, and persistent congestion that persists with fever.

Neurologic sequelae

Intracerebral arteritis, subarachnoid hemorrhage, myelitis, and peripheral neuritis occur 2 to 5 months after the fever subsides in the acute phase of leptospirosis, and individually up to 9 months later.

Among them, occlusive cerebral arteritis is the most common.

The clinical manifestations are hemiparesis and aphasia, which may recur briefly.

Anterior tibial fever

In a very small number of patients, nodular erythema may appear on the skin in front of the tibia (inner calf) on both sides, accompanied by fever, which subsides in about 2 weeks.

Other symptoms

Cardiovascular manifestations

Cardiovascular abnormalities may occur, including myocarditis with heart failure or cardiogenic shock.

More than half of patients with severe leptospirosis have electrocardiographic abnormalities, the most common of which is nonspecific ventricular repolarization disturbances [8].

Vasculitis with limb necrosis may also occur in severe patients, including pediatric patients [9-11].

Medical care

Department of Medicine

Infection Medicine

If you have traveled to an infected area and present with fever, chills, muscle aches, generalized malaise, conjunctival congestion, gastrocnemius muscle tenderness on the posterior side of the calf, and enlarged lymph nodes, please visit the Department of Infectious Diseases promptly.

Fever Clinic

For patients with acute fever, go to the Fever Clinic as soon as possible.

Preparation

Information on how to register, preparation of documents, and frequently asked questions.

Tips for medical treatment

If you have a fever, you can use warm towels to wipe your forehead and armpits to reduce the temperature.

Preparation Checklist

Symptom list

Pay particular attention to the time of onset of symptoms, special symptoms, etc.

Is there a fever? What is the temperature? Is it accompanied by fatigue?

Is there a headache, calf pain or tenderness?

Is there any swelling in the armpits or groin?

Are your eyes red?

Is your skin any yellower than before?

Any nausea, vomiting or diarrhea?

Any cough or hemoptysis?

Medical History Checklist

Any recent contact with animal feces or anything contaminated by it?

Where have you been in the last month? Have you been down in the rice fields or exposed to heavy rains, puddles, or floods?

What is the occupation? Has anyone around you experienced similar symptoms?

Any history of drug allergy?

Have you visited any other hospitals? What were the results? What was the treatment?

Checklist

Test results of the last 1 month, which can be brought to the doctor’s office

Laboratory tests: blood test, urine test, pathogenetic test, cerebrospinal fluid test, etc.

Imaging tests: chest X-ray, etc.

Diagnosis

Diagnosis based on

Medical history

The patient may have the following medical history:

Contact with infected animals or contact with infected water, soil, or food contaminated with leptospirosis in an area where leptospirosis is endemic within 5 to 30 days prior to the onset of the disease.

Experience of fishing in a river, wading and swimming in water, etc.

Clinical manifestations

The following symptoms may be present:

Fever: The onset of the disease is rapid and may be accompanied by chills. Body temperature can reach about 39℃ in a short period of time.

Pain: headache is more prominent, generalized myalgia, common in calves, lower back, thighs and pectoral muscles.

Weakness: generalized weakness, especially leg weakness is obvious.

Conjunctival congestion: pain or photophobia without discharge and persistent congestion, persists after fever.

Gastrocnemius muscle pressure: bilateral pressure and pain on the posterior side of the calf, heavy and not palpable.

Enlarged lymph nodes: most common in inguinal and axillary lymph nodes, soybean to fava bean size, with pressure and pain, without suppuration.

Laboratory Tests

Routine Laboratory Tests

Blood routine: total peripheral blood leukocytes and neutrophils are mildly elevated or normal [1].

Urine routine: about 70% of patients have mild proteinuria, and red blood cells, white blood cells and tubular patterns are seen in the urine.

Hematocrit: Hematocrit is often increased.

Pathogenetic examination

Pathogenetic examination is mainly to check the presence of leptospirosis in patients. There are mainly the following methods:

Dark-field microscopy: about 50% positive rate, helps early diagnosis.

Animal inoculation: it takes about 3～6 days, the positive rate is more than 70%, but it takes longer time.

Blood culture: takes 1～8 weeks to culture, positive rate is 20%～70%. Due to the long incubation time, it is not very helpful for patients in the acute stage.

Nucleic acid test: mostly use DNA probe hybridization and PCR method, which can be used for early diagnosis of leptospirosis.

Serologic examination

Agglutination lysis test is currently the most commonly used leptospirosis serologic diagnostic method in China.

Enzyme-linked immunosorbent assay (ELISA) can be used to determine leptospirosis IgM antibody in serum and cerebrospinal fluid, with high specificity and sensitivity.

Other tests

Cerebrospinal fluid examination

In about 70% of patients with meningoencephalitis, cerebrospinal fluid examination reveals high pressure, mild protein elevation and a small number of leukocytes, usually less than 500 × 106/L, with a predominance of lymphocytes.

Sugar is normal or slightly low, and chloride is normal.

Leptospires may be isolated from the cerebrospinal fluid.

X-ray chest radiograph

X-ray chest radiograph in patients with pulmonary hemorrhagic phenotype shows gross glassy or diffuse punctate, lamellar or fused lamellar shadows in both lungs.

Differential diagnosis

The clinical presentation of leptospirosis is complex, and care should be taken to differentiate it from a variety of febrile illnesses and other diseases.

Upper respiratory tract infection and influenza

Mainly endemic in winter and spring, spread by droplets or aerosols, mainly manifested as upper respiratory symptoms, while leptospirosis has coughing up bloody sputum and rarely runny nose.

Epidemic hemorrhagic fever

Epidemic hemorrhagic fever is most common in winter and spring, often with pinpoint hemorrhagic spots on the skin of the armpits and shoulders, often in a linear distribution; penicillin treatment is ineffective.

Dengue fever and dengue hemorrhagic fever

Dengue fever symptoms are more difficult to distinguish from leptospirosis, which is mainly transmitted by Aedes mosquitoes. The initial fever is low and a characteristic rash occurs; jaundice is rare [12].

Acute jaundice viral hepatitis

Some cases of viral hepatitis initially present with symptoms of viremia such as chills, fever, dizziness and generalized aches and pains, followed by jaundice, similar to jaundiced hemorrhagic leptospirosis.

Hepatitis has a slow onset, low-grade fever in most cases, mild symptoms of infection and toxicity, significant gastrointestinal symptoms, rarely conjunctival congestion, lymph node enlargement and gastrocnemius muscle tenderness.

Epidemic encephalitis B

Epidemic B encephalitis is common in children and often presents with persistent high fever and severe headache.

Meningoencephalitis-type leptospirosis is characterized by coma and convulsions, and a combination of epidemiologic data, pathogenetic and serologic tests helps in the diagnosis [13].

Treatment

Aim of treatment: control transmission, reduce or mitigate visceral damage and complications, and reduce the rate of severe disease and death.

Treatment principle: follow the principle of “three early and one on”, i.e. early detection, early diagnosis, early treatment and local treatment [1].

General treatment

Early bed rest, maintain high-calorie fluid or semi-liquid diet, maintain water and electrolyte balance.

Symptomatic treatment

For high fever, physical cooling and sedation can be given [1].

For severe headache, oral codeine can be given.

For nausea and vomiting, benadryl or prochlorperazine may be given.

In patients with diffuse pulmonary hemorrhagic phenotype, sedation needs to be intensified early by giving hydrocortisone slowly intravenously at an early stage. Depending on the heart failure, cardiotonic drugs may be given.

For patients with jaundice hemorrhagic type, it is important to intensify the treatment of hepatoprotection, detoxification and hemostasis, which can be referred to the treatment of viral hepatitis. If there is renal failure, refer to the treatment of acute renal failure.

Pathogen treatment

Killing the pathogen is the key and fundamental measure in the treatment of the disease, so early application of effective antibiotics is emphasized.

Leptospirosis is sensitive to a variety of antimicrobial drugs, such as penicillin, gentamicin, tetracycline, third-generation cephalosporins and quinolones, etc. It is necessary to choose the appropriate drugs under the guidance of doctors.

Penicillin.

The drug of choice for the treatment of leptospirosis [14], the course of treatment is usually 7 days or until 3 days after the fever subsides.

Patients are prone to Hirschsprung’s reaction after the first dose of penicillin, which is manifested by the sudden onset of chills, high fever, headache, generalized pain, accelerated heart rate and respiration, aggravation of the original symptoms, and a sudden drop in body temperature and chills in the limbs in some patients.

Hirschsprung’s reaction mostly occurs half an hour to 4 hours after the first dose of penicillin, due to the release of toxins from a large number of leptospires killed by penicillin, which is easy to occur when the dose of penicillin is large.

Gentamicin or Doxycycline

Patients with a history of penicillin allergy may be switched to gentamicin or doxycycline [3] with the same regimen as penicillin.

Some studies have shown that doxycycline appears to be safer to use in pregnancy than other tetracyclines [15].

Doxycycline should be considered when leptospirosis is not diagnosed and murine typhus is likely to be present, as it is more effective than azithromycin against murine typhus [15].

Tetracycline.

is usually given orally every 6 hours for 5 to 7 days, and the exact dosage needs to be followed by a physician.

Prognosis

Cure.

The cure of the disease is related to the severity of the disease, the early or late treatment, and the correct or incorrect treatment [1].

The prognosis for mild cases is good.

Recovery is rapid and mortality is low when antibiotics and symptomatic treatment are received within 2 days of onset of illness.

Severe cases, such as diffuse pulmonary hemorrhagic phenotype, hepatic and renal failure or those who do not receive timely and correct treatment, have a poor prognosis and a high case fatality rate.

Elderly and frail patients, pregnant women and those with severe complications have a poorer prognosis and may have sequelae.

The combined morbidity and mortality rate of patients who do not receive active treatment is 2.2%, and up to 19.1% in severe cases [16].

Hazards.

Ocular and neurologic sequelae, if not treated appropriately, are prolonged and vision is not easily restored. The nervous system may suffer from cerebral ischemia due to arteritis, thus causing progressive paralysis.

Infection in pregnant women may lead to fetal death and miscarriage [17].

Daily

Daily Management

Daily diet requires high calorie, high quality protein and easily digestible food.

Bed rest and reduced activity.

Disease monitoring

The disease course is recurrent, so it is important to keep an eye on the symptoms and not to take it lightly.

Take care to recuperate after the mid-stage of the disease to minimize the onset of subsequent illnesses.

Prevention

Comprehensive preventive measures, extermination of rats, good management of pigs/dogs and vaccination are the keys to controlling the prevalence of leptospirosis and reducing the incidence of the disease.

Control of infectious agents

Eradication of rodents