Overview
A parasitic disease caused by the infection of humans by the Leishmania protozoan parasite, which may manifest itself as prolonged irregular fever, enlargement of the liver, spleen and lymph nodes, anemia, emaciation, etc. Antiparasitic treatment is the mainstay of the disease, and antimony is the preferred antimony 5-valent agent. If the treatment is untimely, the patient will die of the complication within 1 to 2 years.
Definition
Black fever, also known as visceral leishmaniasis, is a chronic parasitic disease caused by infection with Leishmania protozoa [1-4], which is transmitted by the bite of whitefly, and is a category C infectious disease under China’s Infectious Disease Control Law.
The infection can be manifested as fever, enlarged liver, spleen and lymph nodes, emaciation, and partial skin pigmentation on the face and hands.
Because of the fever and skin pigmentation, it is called “black fever”.
Pathogenesis
Black fever is an endemic infectious disease, but it is widely distributed, and is prevalent in Asia, Africa, Europe and America. Black fever in China is mainly distributed in the rural areas north of the Yangtze River [1].
There is no obvious seasonality in the onset of black fever, which is more frequent in rural areas than in urban areas, and the infection rate of men is higher than that of women, with the ratio of male to female incidence being 1.5:1 [1-2].
The majority of black fever cases occur in Brazil, East Africa and India, with an estimated 50,000 to 90,000 new cases worldwide each year [5].
Classification
According to different epidemiological characteristics, black fever in China can be categorized into human-origin type (plains type), canine-origin type (hills type) and natural epidemic-origin type (desert type).
Human-origin type: mainly seen in the plains, with more common in older children and young adults.
Canine-origin type: mainly found in hilly and mountainous areas, with the onset of the disease common in children aged 1 to 10 years old.
Natural epidemic type: mainly found in Xinjiang and Inner Mongolia in certain desert areas.
Questions you may be concerned about
What is black fever?
Black fever is an infectious disease caused by Leishmania donovani infection, which can manifest as fever, enlarged liver and spleen lymph nodes, anemia and other symptoms.
Black fever is a chronic endemic infection caused by Leishmania donovani, which can be transmitted by the bite of an insect, the whitefly. Patients tend to have prolonged irregular fever, enlarged liver and spleen lymph nodes, pancytopenia, wasting and increased serum globulin. In addition, patients may also develop skin pigmentation on the face, abdomen, hands and feet.
The course of black fever is recurrent, alternating between remissions and flares, and as the disease progresses, the periods of flares become longer and the periods of remission become shorter.
The gold standard for confirming the diagnosis of the disease is the detection of Leishmania protozoa after puncture smear staining of tissues rich in Leishmania protozoa, such as the spleen, liver, bone marrow, and lymph nodes.
When the above symptoms occur and the cause is not known, the patient should be hospitalized promptly.
Causes
Causes
The disease is transmitted by the bite of a female leishmania lacewing, and there are three basic conditions that lead to epidemics.
Source of infection
Patients and carriers are the main sources of infection in plains infected areas, sick dogs in hill infected areas, and wild animals, such as wolves, jackals, and foxes, in desert areas.
The incubation period varies, with an average of 3 to 5 months [1].
Transmission pathway
The pathogen leaves the source of infection and reaches another infected person.
The bite of a female lacewing is the main mode of transmission of black fever, which may occasionally be transmitted via oral mucosa, broken skin, placenta or blood transfusion.
There are many types of lacewings, but the Chinese lacewing is the most common in China.
Susceptible people
People are generally susceptible to the disease, and most of them can obtain lasting immunity after infection.
Children, adults newly arrived in the infected area, immunodeficient people, such as those who have received organ transplants or other immunosuppressive treatments, are more susceptible to infection.
Pathogenesis
The life history of Leishmania dubliniensis requires two hosts: whiteflies, and humans (mammals).
Leishmania dubliniensis consists of two life stages, the flagellum-free and the pre-flagellate.
The non-flagellated body is found in monocyte-macrophages in humans and mammals and is the mature form, which is pathogenic.
The pre-flagellate, also known as the leydosome, is found in the digestive tract of the whitefly and is its infective stage.
When female lacewings bite, they can inhale the flagellum-free bodies in the blood of the patient or infected animal into the stomach, develop into mature pre-flagellates, proliferate, and gather in large numbers in the rostrum of the lacewing.
At this time, if the lacewing bites a human or other animal host again, a large number of pre-flagellates will invade the skin of the infected person with the lacewing saliva, and some of the pre-flagellates will be phagocytosed by macrophages, and some of them will invade into the blood stream, and arrive at the monocyte-macrophage system of the liver, spleen and bone marrow for mass reproduction, which will lead to the occurrence of the disease.
Symptoms
Main Symptoms
Some patients may be asymptomatic after infection, presenting an asymptomatic infection, which may be related to the parasite population, virulence, genetic susceptibility of the population, and nutritional status [6-7].
The course of the disease in typical patients is mostly recurrent, and periods of remission may occur during the course of the disease, manifested by a decrease in body temperature, reduction of symptoms, spleen shrinkage, and improvement of laboratory blood indexes, but the disease may recur after a few weeks, and the disease may last for several months, and the following manifestations may be observed.
Fever
Most of the patients show long-term irregular fever, which can last for several months, but fatigue and other toxic symptoms can be tolerated, and some patients can continue to work.
Enlargement of spleen, liver and lymph nodes
The spleen is usually progressively enlarged, the liver is mildly to moderately enlarged, and the lymph nodes may be mildly to moderately enlarged, which may be manifested as abdominal bulging and abdominal pain.
Anemia and wasting
Anemia and emaciation may occur in patients in the late stage of the disease, mostly with panic, shortness of breath, pale face, rough skin, and emaciation.
Special types
Cutaneous black fever
Most patients have a history of black fever, and a few patients have no history of black fever.
There may be skin lesions such as skin nodules and maculopapular rashes. The nodules may be in patches and usually do not break down, but they are also often not self-healing.
The lesions may occur anywhere on the body, with the face and neck being the most common.
Patients are generally well and most are able to work normally, and the disease can last for several years.
Lymph node-type black fever
Disease is rare and most often there is no history of black fever, or it can occur at the same time as black fever.
There may be low-grade fever, fatigue, the liver and spleen are not large or only mildly enlarged, and there may be superficial lymph node enlargement, with the inguinal lymph nodes most commonly enlarged, which may be the size of a peanut or a fava bean, and most often have no redness, swelling, or tenderness.
Complications
Complications may occur in the late stage of the disease, such as secondary bacterial infection, acute granulocyte deficiency, necrotizing stomatitis, hemorrhage, malnutrition, etc. The most common complications are secondary bacterial infection and acute granulocyte deficiency.
Secondary bacterial infection
Common secondary bacterial infections are in the respiratory tract, middle ear and oral cavity, which may manifest as bacterial pneumonia, otitis media, necrotizing stomatitis, etc., with fever, cough, pus in the ear and oral ulcers.
Acute granulocyte deficiency
Decrease or even lack of peripheral blood neutrophils can be seen in blood routine.
Consultation
Department of Medicine
Department of Infectious Diseases
If you have a recent history of traveling to a black fever endemic area or mosquito bites, and have fever, malaise, abdominal rumbling, abdominal pain, panic, shortness of breath, or pallor, it is recommended that you consult the Department of Infectious Diseases in a timely manner.
Preparation for medical treatment
Consultation: registration, information preparation, common problems
Tips for seeking medical treatment
Before seeking medical treatment, patients with high fever can first use physical cooling, such as warm towels to wipe the armpits and apply a compress to the forehead.
Preparation List
Symptom list
Pay special attention to the time of onset of symptoms, special manifestations, etc.
Is there fever? How long has the fever been present? What is the highest temperature?
Is there abdominal pain?
Is there panic, shortness of breath, pallor?
Are there any skin nodules, skin ulcers?
When did the above symptoms appear?
List of medical history
Have you been bitten by a lacewing?
Is there any history of travel to black fever endemic areas?
Checklist
Test results in the last 1 month, which can be brought to the doctor’s office
Laboratory tests: routine blood test, blood biochemistry, serum antibody test, etc.
Imaging tests: abdominal ultrasound, abdominal CT, etc.
Diagnosis
Diagnosis based on
Medical history
The patient may be a resident of the black fever endemic area, or a person who has lived in the endemic area during the season of adult whitefly activity (May~September).
Clinical manifestations
There may be prolonged irregular fever, enlarged spleen, liver and lymph nodes, panic, shortness of breath, and emaciation.
On palpation, the doctor may touch the enlarged spleen, liver and lymph nodes, mostly without tenderness; if intrasplenic embolism or hemorrhage occurs, pressure pain in the splenic region may be present.
Laboratory Tests
Blood counts
Typical cases may show a reduction in the white blood cell, red blood cell and platelet counts.
The reduction of white blood cell count is the most obvious, which can be reduced to (1.5-3.5)×109/L, and in severe cases, it can be lower than 1.0×109/L, mainly neutrophils are reduced or even completely disappeared; the anemia is often moderate; platelet count can be significantly reduced, usually (40-50)×109/L [1].
Blood biochemistry
Laboratory tests of alanine aminotransferase and glutamine aminotransferase are mostly normal, occasionally mildly elevated; there may be a significant increase in the globulin count, a decrease in the total number of albumin, and an inversion of the albumin-to-globulin ratio.
Coagulation function
Prolongation of prothrombin time is common.
Pathogenetic examination
Puncture from macrophage-rich liver, spleen, bone marrow, lymph nodes, and smear and culture of the puncture specimen to look for pathogens.
Smear examination
Bone marrow smear staining is commonly used to check for the absence of flagellates, which is simple and easy to perform and has a high positive rate.
Puncture smear of spleen and liver has a higher positive rate, but it is rarely used because of its risk.
Lymph node puncture smears can be used to examine patients who have relapsed after treatment.
In patients with cutaneous and lymph node types, samples and smears can be taken from skin lesions and enlarged lymph nodes.
Culture method
When the smear is negative for a small amount of protozoa, the puncture can be cultured for Leishmania protozoa.
Inoculate the puncture material in specific culture medium, incubate at 22～25℃ for 7～10 days, if active pre-flagellates are detected, it will be judged as a positive result, and this method is more sensitive than the smear method.
Serum immunologic examination
Circulating antigen detection
The circulating antigen appears early in serum, and the content of circulating antigen increases with the increase of the number of protozoa, and the antigen disappears with the death of protozoa, which can be used for early diagnosis, and also can be used for judging the prognosis and evaluating the effect of treatment.
Commonly used methods include monoclonal antibody-antigen spot test, spot enzyme-linked immunosorbent assay, competition enzyme-linked immunosorbent assay and so on.
Serum antibody detection
Antibodies are detected by soluble antigens of the preflagellar body of Leishmania protozoa or antigens of the whole worm. Commonly used methods are indirect fluorescent antibody test, direct agglutination test potency, indirect hemagglutination test and so on.
However, it should be noted that immunocompetent patients with black fever may have high titers of antibodies, HIV-positive patients have no or only low titers of antibodies, and serum antibody tests of cured patients and asymptomatic infected patients may also be positive.
Abdominal ultrasound, abdominal CT
Can be used to evaluate liver and spleen enlargement.
Diagnostic Criteria
Suspected cases
A suspected case can be considered if it fulfills the epidemiologic history of a resident in a black fever endemic area, or a person who has lived in an endemic area during the season of adult lacewing activity, and presents with typical symptoms such as prolonged irregular fever and enlargement of the liver, spleen, and lymph nodes [8].
Clinical diagnosis of cases
Suspected cases with positive immunologic tests as described above are considered as clinically diagnosed cases.
Confirmed cases
Suspected cases with positive pathogenetic tests as described above are considered confirmed cases.
Differential Diagnosis
Malaria
Both malaria and black fever may present with fever, malaise, and splenomegaly, but malaria is usually acute, whereas black fever is a chronic parasitic disease. Blood smears and aetiology can be used to differentiate between the two.
Amebic liver abscess
Patients with amebic liver abscess and black fever may present with abdominal pain, fever, and weight loss, which can often be differentiated by imaging tests such as abdominal CT [9].
Lymphoma
Patients with lymphoma and black fever may present with enlarged lymph nodes, hepatomegaly, splenomegaly, hematopenia, and weight loss, which can be differentiated by histopathologic examination [10].
Treatment
Therapeutic goals: alleviate symptoms, prevent and reduce complications.
Therapeutic principle: anti-parasitic treatment is the mainstay, and 5-valent antimony is preferred.
General treatment
Bed rest, give nutritious, high-calorie, vitamin-rich food.
Maintain fluid and electrolyte balance, prevent and treat secondary infection.
Symptomatic treatment of high fever, can be given to physical cooling, if necessary, can be given to ibuprofen and other antipyretic treatment.
For those with hypersplenism and reduction of the three lineages, leukocyte-raising drugs, iron, folic acid and platelet-raising drugs can be given, and a small number of blood transfusions can be given if necessary.
Antiparasitic treatment
Antimony treatment
5-valent antimony is the drug of choice, and antimony sodium gluconate is commonly used [1,10], which needs to be used under the guidance of a doctor.
Adverse reactions are more frequent, nausea, vomiting, cough, abdominal pain, diarrhea phenomenon, and occasionally leukopenia.
Note that it is contraindicated in patients with pneumonia, tuberculosis, and severe cardiac, hepatic, and renal diseases.
Non-antimony drugs
When antimony is ineffective, non-antimony drugs can be used, such as pentamidine, amphotericin B, but the efficacy is poor.
Surgical treatment
Splenectomy is feasible if there is still obvious enlargement of spleen with hypersplenism after pathogenetic treatment.
Questions you may be concerned about
Is there a vaccine for black fever?
There is no vaccine for black fever.
Black fever, also known as visceral leishmaniasis, is an infectious disease caused by Leishmania donovani infection, which can be transmitted through the bite of a lacewing and has a certain incubation period of about 3 to 4 months.
After the onset of the disease, there will be fever, weakness, swollen lymph nodes and skin rash, and in severe cases, the skin will be dark black.
However, there is currently no vaccine to prevent black fever, patients need to do a good job of preventing mosquitoes and insects, you can use insecticides to repel insects, and if the disease is in an epidemic period, you need to do a good job of isolation measures.
If patients are infected with black fever, they need to be treated with intravenous injection of antimony sodium gluconate under the guidance of a doctor, which can effectively kill Leishmania donovani, and they can also take medicines such as miltefosine capsules and baloneycin sulfate tablets for treatment.
Prognosis
Cure
The prognosis mainly depends on whether the disease is detected early, treated early and whether there are complications.
Patients who receive early and standardized treatment generally have a high cure rate and can obtain lifelong immunity.
If patients are not treated timely, they often die of complications, such as bacterial pneumonia, sepsis and hemorrhage, within one to two years.
Cases without combined serious complications, the course of the disease can persist for decades, and individual cases can recur far after treatment.
Harmfulness
Prolonged fever, enlarged liver and spleen, anemia, and emaciation can occur after infection, affecting the patient’s work and life.
If not treated promptly, the disease may persist for decades, and there is a risk of death when combined with serious complications.
Daily
Daily management
Bed rest is required after the disease, and subsequently, according to the condition, increase the activities appropriately.
Eat more nutritious, high-calorie, vitamin-rich foods.
Keep the living environment with fresh air, sufficient sunlight and relative humidity, and pay attention to oral hygiene by gargling with light salt water.
Prevention
Control the source of infection
Timely treatment of patients, detection and elimination of sick dogs.
Cut off the transmission pathway
Prevent lacewing, eliminate lacewing, and avoid lacewing bites.
In plain areas, insecticides such as deltamethrin can be used to kill lacewings. In hills and desert areas, repellents such as mosquito repellent lotion can be applied to the skin.
Protecting susceptible people
Families in infected areas are well protected at home with fine-hole screen doors and windows.
When working in the field, try to wear long clothes and pants and apply insect repellent to prevent whitefly bites.