Visceral leishmaniasis B55.0

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 29.10.2020

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Synonym(s)

black fever; Dum-dum fever; Dumdum Fever; internal leishmaniasis; Kala-Azar; leishmaniasis furunculosa; splenomegalia tropica; visceral leishmaniasis; Visceral Leishmaniasis

History
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Elliott, 1863; Leishman, 1903; Donovan, 1903

Definition
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Severe, mostly subacute to chronic general disease (also kala-azar of Hindi kala=black, azar=fever) with infestation of the reticulohistiocytic system of spleen, liver and bone marrow by Leishmania donovani. Co-infection with HIV leads to an untreatable form of visceral leishmaniasis with high mortality (Henn GAL et al. 2018).

Pathogen
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In southwestern Asia, Kala Azar is endemic to L. infantum (Persia, Iraq, Yemen, Oman).

In East Africa, Ethiopia, Kenya, Sudan the infection is caused by L. infantum and L. donovani.

L. chagasi causes visceral leishmaniasis in Central and South America.

Occurrence/Epidemiology
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About 90% of all cases occur in Brazil, India, Bangladesh, Nepal and Sudan. In certain regions humans are the only intermediate host of leishmania (anthroponotic infection).

Manifestation
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In endemic areas:

  • About 20% of infected people are children < 9 years
  • 40-50% of those infected are young people < 15 years

With HIV infected persons:

  • In HIV-endemic areas and in Southern Europe, about 70% of those infected are adults.

Clinical features
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The initial skin florescence at the site of inoculation often consists of an inconspicuous papule, which usually goes unnoticed. The incubation period is variable from 3 months to 2 years. After that the systemic phenomena occur.

  • Leading symptoms: fever (80-100% of patients), hepatosplenomegaly where splenogmegaly may be excessive (detectable in > 90% of patients), lymphadenopathy (50-80% of patients), normochromic anaemia with Hb values < 4g/dl , thrombocytopenia with grayish-pale changes in skin color and bleeding tendencies (hence the Hindi term "Kala azar" black disease) such as epistaxis, skin bleeding, bleeding from the GI tract, dysproteinemia with increase in globulin >30g/l (90% of patients) with reversal of the albumin/globulin ratio.
  • Icterus, diarrhoea and ascites are prognostically unfavourable signs and indicate co-infection with HIV-hin ((Henn GAL et al. 2018).
  • Skin lesions (diagnostically not very important): spotty brown-black haemorrhagic spots (hence the name kala-azar), occasionally formation of less specific nodules. the whole integument is dry and scaly, shiny atrophic skin, especially on the legs.
  • Bleeding of the skin and mucous membranes, hair loss.

Untreated, death (mostly due to secondary infections) occurs in 90% of cases.

Laboratory
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normochrome anaemia with Hb values < 4g/dl

Leukopenia (> 80% of patients)

thrombocytopenia (> 70% of patients)

Dysproteinemia with increase of globulin >30g/l (90% of patients) and reversal of the albumin/globulin ratio: albumin <30g/l (90% of patients)

pathological liver values

positive Leishmania serology (> 70% of patients)

Internal therapy
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First-choice remedy: Liposomal Amphotericin B (AmBisome). The toxicity is lower compared to Amphotericin B. The total dose is 20-30 mg/kg bw, divided into at least 5 single doses of 3-4 mg/kg bw each over a period of 10-21 days (e.g. 3-4 mg/kg bw/day on days 0, 1, 2, 3, 4 and 10).

Second-choice agent: Miltefosine (Impavido): 1.5-2.5 mg/kg bw/day p.o. Treatment duration 28 days (capsules to be taken with meals).

Pentavalent antimony preparations (Antimony = Stibium/Sb) are very toxic and should be avoided. Sodium stibogluconate (e.g. pentostam) contains 10% Sb (100 mg/ml), megluminantimonate (e.g. glucantim) contains 8.5% Sb (85 mg/ml). Dosage: 10-20 mg/kg bw/day i.m. (painful) or slowly via small caliber needle i.v. for at least 20 consecutive days or 2 weeks beyond parasitological healing. Caution! Risk of thrombosis. If necessary, combination with Allopurinol.

In other countries other therapy modalities are used, they are particularly important in the prevention of recurrence in HIV patients:

Progression/forecast
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With timely therapy healing in 95% of cases. Untreated mortality is about 80%. Permanent immunity.

Notice! Patients should nevertheless be examined for recurrence every 1/2 year for 2 years.

After visceral leishmaniasis a chronic cutaneous form can develop, which is called post-cala-azar leishmaniasis or post-cala-azar-dermal leishmanoid. Characteristic are maculo-papular and nodular skin lesions. This form occurs in East Africa in about 5% of patients in the convalescence phase.

Prophylaxis
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Insecticides, suitable clothing, mosquito net to avoid mosquito bites.

Aftercare
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Examine patients for recurrence every 1/2 year for 2 years.

Note(s)
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Current therapy recommendations can be found in the AWMF guidelines.

Literature
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  1. Barbosa JFet al. (2015) New Approaches on Leishmaniasis Treatment and Prevention: A Review on Recent Patents. Recent Pat Endocr Metab Immune DrugDiscov
    PubMed PMID: 26392062.
  2. Copeland NK et al (2015) Leishmaniasis: treatment updates and clinical practice guidelines review. Curr Opin Infect Dis 28:426-437
  3. Elliott J (1863). Report on epidemic and remittent fever occurring in parts of Burdwan and Neddea divisions. Bengal Secretarial Office, Calcutta, India pp. 1-23
  4. Donovan C (1903) The etiology of the heterogeneous fevers in India. Br Med J ii: 1401
  5. Henn GAL et al (2018) Is visceral leishmaniasis the same in HIV-coinfected adults?
    Braz J Infect Dis 22:92-98.
  6. Leishman WB (1903) On the possibility of the occurrence of trypanosomiasis in India. Br Med J i: 1252-1254
  7. Lun ZR et al (2015) Visceral Leishmaniasis in China: an Endemic Disease under Control. Clin Microbiol Rev 28: 987-100

Disclaimer

Please ask your physician for a reliable diagnosis. This website is only meant as a reference.

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Last updated on: 29.10.2020