The clinical presentation of visceral leishmaniasis possesses a long incubation period (ranging from a few weeks to even years), a nonspecific symptomatology, and a variable clinical course, and may pose a diagnostic challenge [1] [2] [3] [4]. The two main signs of visceral leishmaniasis are fever and pancytopenia, both being almost universally present in all patients who suffer from this type of leishmaniasis [1] [2]. Fever can range anywhere between 37-40°C and often has an irregular pattern of occurrence [5]. On the other hand, pancytopenia (including thrombocytopenia, anemia, and leukopenia) causes weakness and severe immunosuppression, thus promoting various superinfections of bacterial, viral, or parasitic origin [1] [2] [5]. Opportunistic infections are, in fact, the leading cause of death from visceral leishmaniasis, with mortality rates being as high as 75%-95% in the absence of an early diagnosis and appropriate therapy [1]. The term "kala-azar" (meaning black death) is used to describe visceral leishmaniasis that is restricted to the Old World and caused by Leishmania donovani [1]. Wasting and poor general condition induced by pancytopenia are seen in advanced stages of the disease [6]. In addition to fever and bone marrow suppression, hepatosplenomegaly is another important sign in visceral leishmaniasis, seen in up to 85-100% of patients in some studies [5]. Lymphadenitis is a less frequent manifestation [2] [5].

• Fever

  Herein we report an 11 month-old male infant with diagnosis of kala-azar who presented with pallor, hepatosplenomegaly, failure to gain weight, and no history of fever. [ncbi.nlm.nih.gov]

  A type of leishmaniasis occurring chiefly in India, caused by the protozoan parasite Leishmania donovani and characterized by fever, enlargement of the spleen and liver, progressive anemia and leukopenia, and weight loss. [medical-dictionary.thefreedictionary.com]

  […] ka·la-azar \ ˌkä-lə-ə-ˈzär, ˌka- \ : a severe parasitic disease chiefly of tropical areas that is marked by fever, progressive anemia, leukopenia, and enlargement of the spleen and liver and caused by a leishmania ( Leishmania donovani ) transmitted by [merriam-webster.com]

  Visceral leishmaniasis kālā āzār Other names Black fever, and Dumdum fever Classification D ICD-10: B55.0 ICD-9-CM: 085.0 MeSH: D007898 DiseasesDB: 7070 External resources eMedicine: emerg/296 [en.wikipedia.org]

• Anemia

  A type of leishmaniasis occurring chiefly in India, caused by the protozoan parasite Leishmania donovani and characterized by fever, enlargement of the spleen and liver, progressive anemia and leukopenia, and weight loss. [medical-dictionary.thefreedictionary.com]

  […] ka·la-azar \ ˌkä-lə-ə-ˈzär, ˌka- \ : a severe parasitic disease chiefly of tropical areas that is marked by fever, progressive anemia, leukopenia, and enlargement of the spleen and liver and caused by a leishmania ( Leishmania donovani ) transmitted by [merriam-webster.com]

  Adverse events in the liposomal-therapy group were infusion-related fever or rigors (in 40%) and increased anemia or thrombocytopenia (in 2%); such events in the conventional-therapy group were fever or rigors (in 64%), increased anemia (in 19%), and [ncbi.nlm.nih.gov]

• Malaise

  […] funkcionalno nepismene, kot potrebe po izogibanju morebitnim stereotipom v zvezi s tem profilom ugotavljajo naslednje en Leishmaniasis sl Stari se bo zlomil, pa če bo tekla kri en Visceral leishmaniasis causes systemic disease, presenting with fever, malaise [sl.glosbe.com]

  Common symptoms are fever, malaise, weight loss and anaemia, with swelling of the spleen, liver and lymph nodes in visceral human leishmaniasis. [ecdc.europa.eu]

  […] systemic disease characterized by darkening of the skin as well as the pentad of fever, weight loss, hepatosplenomegaly, pancytopenia, and hypergammaglobulinemia Viscerotropic leishmaniasis: Nonspecific abdominal tenderness; fever, rigors, fatigue, malaise [medscape.com]

  Adverse effects include nausea, vomiting, malaise, elevated amylase and/or liver enzymes, and cardiotoxicity (arrhythmias, myocardial depression, heart failure, ECG changes, cardiac arrest). The incidence of adverse effects increases with age. [merckmanuals.com]

• Chills

  We report the case of a 73-year-old American traveler who presented with 3 weeks of fatigue, fevers, chills, and pancytopenia. [ncbi.nlm.nih.gov]

  It is commonly characterized by fever, chills, vomiting, anemia, hepatosplenomegaly, leukopenia, hypergammaglobulinemia, emaciation, and an earth-gray color of the skin. [icd10data.com]

• Constitutional Symptom

  Kala-azar's classical triad (fever, constitutional symptoms and splenomegaly) was less frequently observed in Visceral Leishmaniasis-HIV patients, as well as jaundice and edema, while diarrhea was more frequent. [ncbi.nlm.nih.gov]

• Splenomegaly

  Infantile VL may begin suddenly, with high fever and vomiting, or insidiously, with irregular daily fever, anorexia, and marked splenomegaly. [ncbi.nlm.nih.gov]

  It can be difficult to diagnose this disease in endemic settings as several causes of febrile splenomegaly exist, notably malaria. [bmj.com]

• Massive Splenomegaly

  infection with Leishmania sp. associated with high fever, weight loss, massive splenomegaly and markedly altered laboratory parameters, is generally fatal if untreated. [ncbi.nlm.nih.gov]

  splenomegaly Laboratory tests may show pancytopenia and hypergammaglobulinaemia Complications include gastrointestinal bleeding, peripheral oedema, acute renal failure and secondary bacterial infections Generalised hyperpigmentation is a late feature [dermnetnz.org]

  There are very few pediatric conditions that can stimulate massive splenomegaly, as observed in our patient and reported in VL [ 20 ]. [ispub.com]

  massive splenomegaly and moderate hepatomegaly), fever, cachexia and weight loss, pancytopenia and hypergammaglobulinemia. Overall, the most common clinical features are anemia, fever, and splenomegaly (26, 29). [pedinfect.com]

• Generalized Lymphadenopathy

  lymphadenopathy, profound weakness and a wasting syndrome [11 ,13,14]. [journals.lww.com]

  Clinical manifestations of VL include recurrent fever, hepatosplenomegaly, generalized lymphadenopathy, pancytopenia, and anemia. Death occurs in the absence of appropriate chemotherapy ( 4 ). [jimmunol.org]

• Cough

  While in Benishangul-Gumuz, the patient was diagnosed with prolonged and intermittentfever, epistaxis, splenomegaly, skin pallor, diarrhea, cough and oedema. [ncbi.nlm.nih.gov]

  An 18-year-old immunocompetent patient was referred to a local hospital with submandibular lymphadenopathy, nonproductive cough, and occasional fever. [intjinfection.com]

  Side-effects include abdominal pain, vomiting, nausea, fatigue, headache, increase of liver enzymes, nephrotoxicity, arthralgia, fever, rash, cough, pneumonia, pancytopenia and reversible peripheral neuropathy. [clinicalmicrobiologyandinfection.com]

• Abdominal Distension

  On general physical examination, the patient was found to be thin built, pale, and afebrile with abdominal distension. Left submandibular and left axillary lymph nodes were enlarged and measured 1.5 cm in diameter. [cytojournal.com]

  Fifty-seven percent of the patients had abdominal distension, and 49% had anorexia. Fever and splenomegaly were present in more than 95% of the patients. [pedinfect.com]

  Patients presenting with abdominal distension and nausea showed higher IC-induced production of IL-6 ( p 0.0400 and 0.0371, respectively; data not shown), whereas IC from patients jaundiced at the time of blood sampling induced higher levels of GM-CSF [jimmunol.org]

• Hepatosplenomegaly

  VL should be considered in the differential diagnosis in returning travellers presenting with prolonged fever, hepatosplenomegaly and/or pancytopenia. [ncbi.nlm.nih.gov]

• Hepatomegaly

  CASE PRESENTATION: A 9 year-old boy was admitted to Imam Reza teaching hospital in Mashhad, Iran in 2010 with fever, sweating, abdominal distention, massive hematemesis, weight loss, huge splenomegaly and hepatomegaly. [ncbi.nlm.nih.gov]

• Liver Fibrosis

  The differential diagnosis includes liver fibrosis, abnormal blood flow due to splenic vein thrombosis or portal vein obstruction, and liver cirrhosis due to chronic viral hepatitis B or C, fatty liver, and alcohol use. [acgcasereports.gi.org]

• Grieving

  AIDS Res Hum Retroviruses 10: 1619-1627. [ Links ] Dulley J, Grieve P 1975. A simple technique for eliminating interference by detergents in the Lowry method of protein determination. [doi.org]

A detailed patient history and a thorough physical examination are the first and perhaps crucial steps for making an initial diagnosis of visceral leishmaniasis. The vast majority of patients (> 90%) who suffer from visceral leishmaniasis come from six countries of the world: India, Bangladesh, Sudan, South Sudan, Ethiopia, and Brazil [6] [7] [8]. For this reason, the physician should conduct a detailed patient history that will cover recent travel to endemic countries, as well as possible exposure to sand flies in the last few years. After assessing the course of symptoms and their progression during the interview, a meticulous physical examination, particularly abdominal palpation, will reveal either hepatomegaly, splenomegaly, or both. In order to solidify the diagnosis, laboratory and microbiological tests need to be conducted. A basic complete blood count (CBC) is sufficient to detect pancytopenia, while directed diagnostic testing for Leishmania is broadly divided into indirect and direct methods. Serological testing (specifically enzyme-linked immunosorbent assay, or ELISA, and fluorescence antibody testing) is widely used as the main indirect test that has good sensitivity/specificity [1] [2] [3] [4]. Detection of antigen rk39 through ELISA is a very reliable procedure and is used by many laboratories over the world [3] Conversely, identification of the parasite by light microscopy and Giemsa staining from blood samples is a relatively easy and effective procedure, while lymph node, liver, spleen, or even bone marrow samples might be used for evaluation, but the risks of bleeding (particularly in the case of spleen and bone marrow) often outweigh the benefit of confirming the diagnosis histologically [1] [2] [3] [4].

• Hyperglobulinemia

  In active VL, macrophages host the replicating amastigotes in phagolysosomal compartments leading to splenomegaly, hepatomegaly, hyperglobulinemia, anemia, weight-loss, incessant fever and ultimately death if not treated. [books.google.com]

  Serum biochemistry revealed hyperproteinemia 100.0 g/L [54.0 – 82.0 g/L], hyperglobulinemia 83.0 g/L [23.0 – 52.0 g/L] and hypoalbuminemia 18.0 g/L [25.0 – 44.0 g/L]. [parasitesandvectors.biomedcentral.com]

  The most consistent serum biochemistry findings in dogs with clinical canine leishmaniosis are serum hyperproteinemia with hyperglobulinemia and hypoalbuminemia, frequently expressed by a decreased albumin:globulin ratio. [msdvetmanual.com]

• Brugia Malayi

  Murthy, Cross reactive molecules of human lymphatic filaria Brugia malayi inhibit Leishmania donovani infection in hamsters, Acta Tropica, 10.1016/j.actatropica.2015.08.018, 152, (103-111), (2015). [doi.org]

The estimated cost of treatment with amphotericin B deoxycholate was USD 1,522.70. [ncbi.nlm.nih.gov]

Visceral leishmaniasis, associated with HIV/AIDS coinfection, is becoming a more aggressive disease, complicating an accurate prognosis. [ncbi.nlm.nih.gov]

References:[3][6][7] Leishmaniasis Summary Epidemiology Etiology Cutaneous leishmaniasis Clinical features Diagnostics Treatment Prognosis Visceral leishmaniasis Clinical features Diagnostics Treatment [amboss.com]

Some researchers have noted that patients with jaundice had worse prognosis [21]. [intechopen.com]

The presentation and prognosis will vary depending on the species involved. [dermnetnz.org]

[…] megutamineantimoniate Non drug therapy-local heat therapy, cryo 30. 3.MUCUCUTANEOUS LEISHMANIASIS * Pentavalent antimony IVIM 20mgkg qd for 28 days * Amphotericine B(deoxycholate) IV 1mgkg qd (total 20-40mg) * Pentamidine IVIM 2-4mgkg thricewkly for 15 doses 31. prognosis [slideshare.net]

CONCLUSIONS: VL in HLH patients does not exclude a genetic etiology and requires structured clinical management. [ncbi.nlm.nih.gov]

References:[3][6][7] Leishmaniasis Summary Epidemiology Etiology Cutaneous leishmaniasis Clinical features Diagnostics Treatment Prognosis Visceral leishmaniasis Clinical features Diagnostics Treatment [amboss.com]

/epidemiology* DNA, Intergenic/genetics DNA, Protozoan/blood DNA, Protozoan/genetics Enzyme-Linked Immunosorbent Assay Female HIV Infections/complications HIV Infections/epidemiology* Humans Iran/epidemiology Leishmania infantum/immunology Leishmania [ncbi.nlm.nih.gov]

Ref: WHO/CTD/LEISH/98.23 Leishmania/HIV co-infection - Epidemiological analysis of 692 retrospective cases. [who.int]

Knowledge gaps were identified in relation to pathophysiology, risk factors, and the role of PKDL patients in transmission. [dndi.org]

This two-page spread overviews the pathophysiology of visceral leishmaniasis—also known as Kala Azar, or black fever. [inessaskaya.com]

Useful For Suggests clinical disorders or settings where the test may be helpful Diagnosis of active visceral leishmaniasis Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test Visceral [mayomedicallaboratories.com]

Verner–Morrison syndrome and WDHA syndrome (watery diarrhea, hypokalemia, achlorhydria) (Rom J Morphol Embryol 2017;58:371) ICD coding ICD-10: C7A.8 - other malignant neuroendocrine tumors ICD-10: E16.8 - other specified disorders of pancreatic internal secretion Pathophysiology [pathologyoutlines.com]

Pathophysiology Modes of transmission In leishmaniasis, the obligatory intracellular protozoa are transmitted to mammals via the bite of the tiny 2- to 3-mm female sandfly of the genus Phlebotomus in the Old World (Eastern Hemisphere) and Lutzomyia in [emedicine.com]

Key strategies for prevention are listed below: Early diagnosis and effective prompt treatment reduces the prevalence of the disease and prevents disabilities and death. [who.int]

Therefore, clinicians especially in endemic areas are highly recommended to include kala-azar among differential diagnosis of unexplained anemia without fever to prevent misdiagnosis of this potentially fatal, but treatable condition. [ncbi.nlm.nih.gov]

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6. Singh OP, Sundar S. Developments in Diagnosis of Visceral Leishmaniasis in the Elimination Era. J Parasitol Res. 2015;2015:239469.
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8. Alvar J, Vélez ID, Bern C, et al. Leishmaniasis worldwide and global estimates of its incidence. PLoS ONE. 2012;7(5)