bubble_chart Overview

The amastigote of Leishmania donovani primarily resides in the macrophages of organs such as the liver, spleen, bone marrow, and lymph nodes, often causing systemic symptoms like fever, hepatosplenomegaly, anemia, and epistaxis. In India, patients frequently exhibit dark pigmentation on the skin along with fever, hence the disease is also known as Kala-azar, meaning "black fever." Due to its high pathogenicity, spontaneous recovery is rare, and without treatment, patients often succumb to complications.

bubble_chart Epidemiology

Leishmaniasis is a zoonotic disease. In addition to transmission between humans, it can also spread between animals and humans, as well as between animals. The disease is widely distributed, prevalent in Asia, Europe, Africa, Latin America, and other regions. It is primarily endemic in China, India, and countries along the Mediterranean coast. In China, black Rebing is prevalent in vast rural areas north of the Yangtze River, including 16 provinces, municipalities, and autonomous regions such as Shandong, Hebei, Henan, Jiangsu, Anhui, Shaanxi, Gansu, Xinjiang, Ningxia, Qinghai, Sichuan, Shanxi, Hubei, Liaoning, Inner Mongolia, and the suburbs of Beijing. In recent years, cases have mainly occurred annually in Gansu, Sichuan, Shaanxi, Shanxi, Xinjiang, and Inner Mongolia, with patients concentrated in southern Gansu and northern Sichuan.

Depending on the source of the pestilence, black Rebing can be roughly divided into three distinct epidemiological types: anthroponotic, zoonotic (canine), and natural reservoir types, represented typically by the black Rebing in India, the Mediterranean basin, and the deserts of Central Asia, respectively. Due to China's vast territory and the wide distribution of black Rebing, which includes three different types of regions—plains, hills, and deserts—all three types of black Rebing can be observed domestically. They exhibit significant differences in terms of epidemic history, the relationship between Chinese Taxillus Herb parasites and hosts, as well as immunity, and each has its own distinct epidemiological characteristics.

bubble_chart Pathogenesis

Amastigotes multiply within macrophages, leading to extensive destruction and proliferation of these cells. Macrophage proliferation is primarily observed in organs such as the spleen, liver, lymph nodes, and bone marrow. Plasma cells also proliferate significantly. The proliferation of cells is the fundamental cause of the enlargement of the spleen, liver, and lymph nodes, with splenomegaly being the most common, occurring in over 95% of cases. In the late stage (third stage), the tissue hardens due to the proliferation of reticular fibrous connective tissue. Patients exhibit a decrease in plasma albumin levels and an increase in globulin levels, resulting in an inverted albumin-globulin ratio. Among the globulins, the titer of IgG rises. The blood shows a reduction in red blood cells, white blood cells, and platelets, caused by hypersplenism and the massive destruction of blood cells within the spleen. Additionally, immune-mediated hemolysis is a significant factor contributing to anemia. Leishmania parasites reside and multiply within macrophages, and their antigens can be expressed on the surface of macrophages. The host's immune response to Leishmania is cell-mediated, with activated macrophages serving as the effector cells. These cells kill amastigotes by generating reactive oxygen species intracellularly. The necrosis of macrophages containing amastigotes can eliminate the parasites. Recent studies have shown that antibodies also play a role in the host's process of killing Leishmania parasites.

bubble_chart Pathological Changes

Due to thrombocytopenia, patients often experience symptoms such as epistaxis and gum bleeding. The occurrence of proteinuria and hematuria may be caused by glomerular amyloidosis and the deposition of immune complexes in the glomeruli.

bubble_chart Clinical Manifestations

Cell proliferation is the fundamental cause of spleen, liver, and lymph node enlargement, with splenomegaly being the most common, occurring in over 95% of cases. In the late stage [third stage], the tissue hardens due to the proliferation of reticular fibrous connective tissue. Patients exhibit a decrease in plasma albumin levels and an increase in globulin levels, resulting in an inverted albumin-to-globulin ratio. Among the globulins, IgG titers are elevated. The blood shows reductions in red blood cells, white blood cells, and platelets, which is caused by hypersplenism leading to the massive destruction of blood cells in the spleen. Additionally, immune hemolysis is another significant cause of anemia. Cutaneous Rebing: Skin lesions concurrent with visceral involvement occur in 58.0% of cases; in some patients (32.3%), they appear years after the disappearance of visceral disease; and a small number (9.7%) are primary cases with no history of visceral infection or cutaneous Rebing. Skin injuries are mostly nodular, with a few being depigmented. The nodules present as granulomas of varying sizes or dark-colored papules, commonly found on the face and neck, where amastigotes can be detected within the nodules. Lymph node type Rebing: The hallmark of this type is the absence of a history of Rebing, with localized lymph node enlargement of varying sizes, superficial location, absence of tenderness or redness, and eosinophilia. Lymph node biopsies may reveal amastigotes within epithelioid cells.

bubble_chart Auxiliary Examination

Common methods for pathogen examination include:

(1) Puncture examination:

1) Smear method: Bone marrow puncture material is smeared, stained, and examined under a microscope. This is the most commonly used method, with a protozoan detection rate of 80–90%. Lymph node puncture should target superficial and enlarged nodes, with a detection rate of 46–87%. Lymph node biopsy can also be performed. Splenic puncture has a higher detection rate, reaching 90.6%–99.3%, but it is less safe and rarely used.

2) Culture method: The aforementioned puncture material is inoculated into NNN culture medium and placed in an incubator at 22–25°C. After one week, if actively motile promastigotes are observed in the culture, the result is considered positive. Strict aseptic techniques must be followed during the procedure and culture process.

3) Animal inoculation method: The puncture material is inoculated into susceptible animals (such as hamsters, BALB/c mice, etc.). After 1–2 months, the liver and spleen are harvested for imprint or smear preparation, stained with Wright's stain, and examined under a microscope.

(2) Skin biopsy: A sterile needle is used to puncture the skin at the nodule site to collect a small amount of tissue fluid, or a scalpel is used to excise a small amount of tissue for smear preparation, staining, and microscopic examination.

bubble_chart Diagnosis

Immunodiagnostic methods:

(1) Detection of serum antibodies: such as enzyme-linked immunosorbent assay (ELISA), indirect hemagglutination test (IHA), counter immunoelectrophoresis (CIE), indirect fluorescence test (IF), direct agglutination test, etc. These methods have a high positive rate but also a high false-positive rate. In recent years, the use of molecular biology methods to obtain pure antigens has reduced the false-positive rate.

(2) Detection of serum circulating antigens: The monoclonal antibody antigen spot test (McAb-AST) is used to diagnose black Rebing, with a high positive rate, good sensitivity, specificity, and reproducibility. It requires only a minimal amount of serum and can also be used for efficacy evaluation.

Molecular biology methods: In recent years, polymerase chain reaction (PCR) and DNA probe techniques have achieved good results in detecting black Rebing, with high sensitivity and specificity. However, the procedures are relatively complex and have not yet been widely adopted.

bubble_chart Treatment Measures

The injection of low-toxicity, high-efficiency sodium stibogluconate achieves a cure rate of 97.4%. For antimony-resistant patients, pentamidine, stilbamidine, or hydroxystilbamidine isothionate may be used. In cases where multiple drug treatments fail and the spleen is severely enlarged with hyperfunction, splenectomy may be considered.

bubble_chart Cure Criteria

After thorough treatment, if no systemic symptoms and signs appear within 3 to 6 months, it can be confirmed as cured.

bubble_chart Prognosis

After treatment with specific drugs, patients have a high recovery rate and generally do not get reinfected, gaining lifelong immunity.

bubble_chart Prevention

Treating patients, controlling sick dogs　Sick dogs are to be captured and killed. However, managing dogs in hilly and mountainous areas does present certain difficulties, and effective measures need to be found to control them.

Killing sandflies and preventing sandfly bites　In plain areas, killing worms agents are used for indoor and livestock shed residual spraying to eliminate Chinese sandflies. In mountainous, hilly, and desert areas, measures to prevent and repel sandflies are taken for wild or semi-wild sandflies to reduce or avoid sandfly bites.

As for the distribution of natural epidemic foci and reservoir hosts in endemic areas of natural foci, these issues still need to be clarified, and their control strategies also require further research.