Visceral leishmaniasis is a chronic infectious protozoal disease with damage to the liver and spleen, the development of anemia and cachexia. Other symptoms are fever, enlarged lymph nodes, skin manifestations. Diagnostics includes the identification of the pathogen from blood and biopsies of internal organs, less often by biopsy on rodents, the search for antibodies to the pathogen. Treatment consists of a course of etiotropic drugs (mainly pentavalent antimony) and correction of organ dysfunction as symptomatic therapy. In some cases, hemotransfusions are indicated.
B55.0 Visceral leishmaniasis
Visceral leishmaniasis (dum-dum fever, kala-azar, black fever) belongs to vector-borne infections caused by protozoa. In 1903, the English pathologist Leishman, together with the Italian scientist Donovan, described the morphology of organ lesions and isolated the pathogen. In honor of the researchers, the infectious agent was named Leishmania donovani. The disease is most common in tropical and subtropical countries, the seasonal increase in morbidity depends on the characteristics of the vector’s life cycle and falls on the period from May to November.
The causative agent of infection is the simplest parasitic microorganism Leishmania. Sources and reservoirs of infection are warm-blooded wild and domestic animals (rodents, sloths, foxes, dogs), people. The path of infection is mainly transmissible, the carriers are female mosquitoes of the genus Phlebotomus. There are data on isolated cases of infection during blood transfusions, transmission of leishmania from mother to fetus, when using non-sterile medical instruments and needles during intravenous administration of narcotic drugs.
In its development, leishmanias need to go through two stages: non-flagellated and flagellated in the human body or animal and carrier, respectively. Amastigotes live inside cells, are deprived of the ability to move, promastigotes have flagella for active movements in space. Being inside the female mosquito, leishmania actively reproduce in the digestive canal of the insect, after which they move to the proboscis. The most susceptible to infection are children under 5 years old, young men, agricultural workers, tourists, patients with HIV infection, oncopathologies.
At the site of the vector bite, a primary affect is formed in the form of a granuloma, which consists of macrophages with leishmania multiplying inside, reticulocytes, epitheliocytes and giant cells. After a while, the granuloma undergoes reverse development, less often scarring, and pathogens in macrophages with lymph and blood flow enter the internal organs. In the normal state of the immune system, the destruction of the affected cells occurs. In the case of immunodeficiency, leishmanias multiply at an increased rate, affect parenchymal organs.
This leads to the appearance of inflammatory changes, active fibrosis and an increase in the size of organs. In the hepatic tissue, pathohistological examination reveals areas of interlobular fibrosis and hepatocyte dystrophy, in the lymph nodes – dystrophic changes in the germinal center and bone marrow aplasia, in the spleen – pulp atrophy, zones of infarcts, necrosis and hemorrhagic infiltrates. With a prolonged course of visceral leishmaniasis, amyloidosis of internal organs occurs.
The division of visceral leishmaniasis into rural and urban types implies different sources of infection (domestic and wild animals), as well as the severity of the pathology – it is believed that the urban type of the disease is more benign. There are acute, subacute and chronic variants of organ leishmaniasis. The most favorable course is characterized by the chronic form, the acute type of this protozoal infection is most often found in children, characterized by rapid development of symptoms and frequent deaths. For the subacute variant, the presence of complications is typical.
Symptoms of visceral leishmaniasis
The incubation period ranges from 20 days to 1 year, more often 3-5 months. The manifestation of the disease is characterized by a gradual onset, the appearance of a pale pink skin papule at the site of the introduction of the pathogen, followed by a depigmentation site (leishmanoid). There is weakness, causeless fatigue, decreased appetite, weight loss. In the future, fever joins up to 39-40 ° C, which proceeds with alternating high and normal body temperature for several months.
There is a painless increase in all groups of lymph nodes, a change in their consistency to tight-elastic. Patients with visceral leishmaniasis almost always note heaviness and discomfort in the hypochondria. With the progression of the disease, hepatosplenomegaly is observed with the appearance of edema and an increase in the abdomen. The amount of urine excreted decreases. Due to the development of hypersplenism and bone marrow lesions, bleeding occurs. Shortness of breath, ulcerative-necrotic lesions of the oral cavity, pallor of the skin, defecation disorders are detected.
The most frequent complications (thrombohemorrhagic syndrome, granulocytopenia, agranulocytosis) are associated with damage to the hematopoietic system, resulting in necrosis of the tonsils, oral mucosa and gums (noma). Edematous ascitic syndrome in visceral leishmaniasis occurs due to liver involvement, is accompanied by chronic heart failure, gastrointestinal disorders (enterocolitis), nephritis, decreased libido, oligo- and amenorrhea. Cases of bacterial pneumonia are characteristic due to the high standing of the diaphragm and a decrease in the respiratory capacity of the lungs. Rare complications include ruptures of the spleen, hemorrhagic shock, DIC syndrome.
The determination of the visceral form of leishmaniasis requires an examination by an infectious disease specialist, according to indications, consultations of other specialists are appointed. It is important to clarify with the patient the fact of being in endemic areas of the globe during the previous five years, the presence of vaccination against leishmaniasis, the type of professional occupation. Laboratory and instrumental methods of disease verification include:
- Physical examination. During an objective examination, pallor, dryness, thinning of the skin, the presence of ulcers in the oral cavity attracts attention. Lymph nodes are dense, enlarged, painless. During auscultation, the heart tones are muffled, tachycardia, noises are heard, areas of weakened breathing can be detected in the lungs. Palpation of the abdomen is painless, the size of the spleen and liver are dramatically increased. Peripheral edema, ascites are often found.
- Laboratory tests. Signs of leishmaniasis in the general blood test are anemia, poikilocytosis, anisocytosis, leukopenia, neutropenia, aneosinophilia, thrombocytopenia, a sharp acceleration of ESR. Biochemical parameters were changed in the direction of increasing ALT, AST, CRP, creatinine and urea, hypoalbuminemia. There is an increase in blood clotting time. In the general clinical analysis of urine, an increase in the density of urinary sediment, proteinuria, hematuria is noted.
- Identification of infectious agents. To detect leishmania, microscopy is performed, biological preparations and blood are seeded, less often bioassays on hamsters. Serological diagnostics (ELISA) is aimed at detecting anti-leishmaniasis antibodies. The use of the intradermal Montenegro test is an indirect method of confirming the diagnosis during the convalescence period, it is used in epidemiological studies in the population.
- Instrumental techniques. Chest X-ray is performed to exclude pneumonia, tuberculosis lesions. Abdominal sonography visualizes an increase in the size of the liver, spleen, signs of portal hypertension, the presence of ascites. Ultrasound and biopsy of lymph nodes, sternal puncture, bone marrow trepanobiopsy, diagnostic thoracoscopy and laparoscopy are performed according to indications.
Differential diagnosis of leishmaniasis of internal organs is carried out with malaria, which is characterized by jaundice and the triad “chills-fever-sweat”; brucellosis with its pathognomonic lesions of the musculoskeletal system, nervous, reproductive, cardiovascular systems and skin; typhoid fever, the clinical features of which are typhoid status, relative bradycardia and intestinal paresis. Influenza is characterized by an acute onset and the addition of symptoms of damage to the upper respiratory tract, as well as seasonality in the cold season.
Tuberculosis is manifested by prolonged subfebrility, rarely dry cough and symptoms of dysfunction of organs involved in the pathological process; often the diagnosis is verified only by laboratory and instrumental methods. The similarity of the clinical symptoms of the disease is observed with pathologies such as leukemia and lymphogranulomatosis, with these pathologies, the diagnostic criteria are the data of blood tests and bone marrow biopsies. Sepsis is clinically similar, but usually has a primary lesion (wound, purulent formation, etc.).
Treatment of visceral leishmaniasis
Patients with this disease are hospitalized in a hospital. It is imperative to limit the possibility of contact with mosquitoes, so mosquito nets are installed above the beds and in the window openings. Bed rest is indicated up to stable normal body temperature figures for 3-5 days, due to the risk of rupture of the spleen with its significant increase, sharp bends, turns, lifting weights of more than 10 kg are not recommended. The diet provides high-calorie, protein-rich food, the water load is selected individually.
Etiotropic therapy of visceral leishmaniasis should include antimony preparations (sodium stibogluconate) or pentamidine, miltefosine, liposomal amphotericin B. Some studies have shown the effectiveness of therapeutic administration of derivatives of pentavalent antimony in combination with paromomycin sulfate, while reducing the duration of treatment. Patients with complications, HIV infection, severe concomitant diseases are recommended course administration of amphotericin B as the first line of treatment for visceral leishmaniasis.
Severe anemia is an indication for erythrocyte hemotransfusions, less often the introduction of thrombomass and donor leukocytes is required. Correction of anemia consists in long–term administration of iron preparations, according to indications – colony-stimulating factors. Symptomatic treatment involves detoxification, taking antipyretics (aspirin – with caution), antibiotics in case of secondary infections. An important component of treatment is the fight against edema, among other things, diuretics and albumin solutions are included in the therapy plan.
Prognosis and prevention
The prognosis for early diagnosis is favorable, with the exception of cases of the disease in HIV-infected patients – in this category of patients, even weakly pathogenic strains of leishmania cause organ lesions. The duration of treatment is 14-30 days, the observation of convalescents takes 4-6 months due to possible relapses of leishmaniasis. In 17% of treated patients, symptoms of post-calcareous dermal leishmaniasis may be detected within 5 years after recovery, diagnostic and treatment protocols for which have not been definitively developed.
Specific prevention consists in the planned introduction of a live vaccine, it is recommended to persons living or planning a long or short stay in endemic territories, tourists. The drug should be administered in winter or autumn at least three months before the trip. Non-specific measures to prevent visceral leishmaniasis include timely detection, isolation and treatment of patients, the use of mosquito nets, vaccination of dogs, removal of landfills, disinsection and deratization measures. The fight against mosquitoes consists, among other things, in draining swamps, basements and vegetable storages.