Visceral leishmaniasis generally conforms to the following cardinal signs of prolonged fever, anemia, leukopenia, splenomegaly and hypergammaglobulinemia. Cutaneous leishmaniasis may or may not present as a nodule at the site of the sandfly bite.

Generally, these presenting signs and symptoms governs the majority of leishmaniasis cases:

• Systemic signs of fever, weight loss, fatigue and dizziness are common in leishmaniasis. Fever is an immune response to the invading protozoan while dizziness and fatigue is anemia related. Weight loss is due to muscle wasting.
• Integumentary system: Skin may appear hyperpigmented at the forehead, abdomen, hands and feet. Jaundice may ensue with hepatic involvement.
• Head and neck: Signs of gum bleeding and epistaxis may be observable in some cases. Disfiguring lesions of the lips and nose may be a late sign of cutaneous leishmaniasis
• Abdominal enlargement due to splenomegaly and in some cases hepatomegaly.
• Extremities: Generalized lymphadenopathy may be observed in visceral leishmaniasis.

• Fever

  The term "kala-azar" comes from India where it is the Hindi for black fever. The disease is also known as Indian leishmaniasis, visceral leishmaniasis, leishmania infection, dumdum fever, black sickness, and black fever. [medicinenet.com]

  Other symptoms of systematic visceral leishmaniasis can include a fever that continues for weeks and even be in cycles, night sweats, stomach pains, thinning hair, and graying of the skin. [microbewiki.kenyon.edu]

  Vomiting Adults usually have a fever for 2 weeks to 2 months, along with symptoms such as fatigue, weakness, and appetite loss. [nlm.nih.gov]

  VL causes fever, weight loss, spleen and liver enlargement, and, if not treated, death. [dndi.org]

  Independent (1998) This parasite causes leishmaniasis, a disease that brings severe fever, weight loss, joint pain and swelling of the spleen and liver. New Scientist (1999) Log in to comment on this word. [web.archive.org]

• Weight Loss

  VL causes fever, weight loss, spleen and liver enlargement, and, if not treated, death. [dndi.org]

  Independent (1998) This parasite causes leishmaniasis, a disease that brings severe fever, weight loss, joint pain and swelling of the spleen and liver. New Scientist (1999) Log in to comment on this word. [web.archive.org]

  People with this form usually have fever, weight loss, and an enlarged spleen and liver. Leishmaniasis is found in parts of about 88 countries. Most of these countries are in the tropics and subtropics. [medlineplus.gov]

  Symptoms, which include fever, weight loss, reduction in the number of white blood cells, and enlargement of the spleen and liver, usually appear two months or more after infection. The disease is usually fatal if not treated. [britannica.com]

  The most important clinical manifestation of visceral leishmaniasis is kala-azar (Hindi for “black fever”), which presents with fever, weight loss, hepatosplenomegaly, and immunosuppression. [amboss.com]

• Asymptomatic

  Usually asymptomatic infection does not persist for more than one year, but rarely asymptomatic infection may last for decades. [29] However, with the advances in diagnostic techniques such asymptomatic cases of leishmaniasis can be diagnosed comparatively [ijmm.org]

  The rate of asymptomatic carriers in blood was assessed with the Scanelis assay: 6%. If a cutaneous sample was collected, the detected load must be taken into account to interpret the result ( contact us for interpretation of results). [scanelis.com]

  Biomarkers of Asymptomatic Infection Many of the articles in this Research Topic insist on the importance of identifying biomarkers of asymptomatic infection. [frontiersin.org]

  It is not known which patients are at highest risk of disease progression, which role parasite/host/HIV factors play in the asymptomatic infection phase, and what the diagnostic values of existing Leishmania infection markers are. [clinicaltrials.gov]

  Despite T-cell-dependent immune responses, which produce asymptomatic and self-healing infection, or appropriate treatment, intracellular infection is probably life-long since targeted cells (tissue macrophages) allow residual parasites to persist. [ncbi.nlm.nih.gov]

• Anemia

  […] any of a number of species of protozoa in the genus leishmania; there are four major clinical types of this infection: cutaneous (old and new world), diffuse cutaneous, mucocutaneous, and visceral; visceral is characterized by fever, chills, vomiting, anemia [icd9data.com]

  Complications The majority of the complications in leishmaniasis is due to the relative anemia, leukopenia and thrombocytopenia in patients. [symptoma.com]

  Symptoms of visceral leishmaniasis include lesions to internal organs (for example, spleen, liver, lymph nodes, or the bone marrow) that result in organ enlargement, fever, anemia, and low blood platelets ( thrombocytopenia ) and can be life threatening [emedicinehealth.com]

  They both have a history of febrile splenomegaly, anemia, and pallor of mucous membranes. Visceral leishmaniasis was confirmed by parasitological diagnosis (positive bone marrow smear and screening of anti-L. infantum antibodies). [ncbi.nlm.nih.gov]

  Our patients had varying degrees of anemia associated with leukopenia and thrombocytopenia. Anemia seems to occur when the spleen becomes palpable and progresses with its gradual increase; this opinion is shared by others [27, 28]. [intechopen.com]

• Weakness

  Weakness increases as the disease gets worse. [nlm.nih.gov]

  Kala azar presents after two to eight months, with more generalised symptoms including prolonged fever and weakness. [msfindia.in]

  Kala azar presents after two to eight months with more generalized symptoms including prolonged fever and weakness. [doctorswithoutborders.org]

• Splenomegaly

  Both patients were cured in two months; defervescence, reduction of splenomegaly, and healing of cutaneous lesions were all observed. [ncbi.nlm.nih.gov]

  Visceral leishmaniasis generally conforms to the following cardinal signs of prolonged fever, anemia, leukopenia, splenomegaly and hypergammaglobulinemia. Cutaneous leishmaniasis may or may not present as a nodule at the site of the sandfly bite. [symptoma.com]

  Visceral manifestations include pronounced splenomegaly (hard, non-tender) and to a lesser extent hepatomegaly. [wynman.com]

  Visceral leishmaniasis causes splenomegaly that is not always distinct from other forms of splenomegaly. Reported cases suggest that multiple nodular lesions in the spleen may occur 4-6. Promoted articles (advertising) [radiopaedia.org]

  Fever, weakness, abdominal pain, mucosal bleeding, and splenomegaly are the most common findings in VL. Hepatomegaly is seen in more than half of the cases. [intjinfection.com]

• Generalized Lymphadenopathy

  Extremities: Generalized lymphadenopathy may be observed in visceral leishmaniasis. The presence of the cardinal signs mentioned above and the history of travel to endemic areas for leishmaniasis clinches the diagnosis of the disease. [symptoma.com]

  Other manifestations may include generalized lymphadenopathy; hyperpigmented skin of the forehead, abdomen, hands, and feet in light-skinned persons; skin lesions in dark-skinned persons; signs of bleeding (petechiae, epistaxis, bleeding gums); jaundice [wynman.com]

  These symptoms are accompanied by an intermittent fever and some generalized lymphadenopathy. [en.wikivet.net]

• Pertussis

  Pertactin-Negative and Filamentous Hemagglutinin-Negative Bordetella pertussis, Australia, 2013–2017 [PDF - 1.61 MB - 4 pages] Z. Xu et al. During the 2008–2012 pertussis epidemic in Australia, pertactin (Prn)–negative Bordetella pertussis emerged. [cdc.gov]

  The use of live vaccines has had many problems, including the development of large uncontrolled skin lesions, exacerbation of psoriasis and other skin diseases, and even immunosuppression as determined by low responses to the diphtheria, pertussis, and [doi.org]

  During his tenure at the FDA, Baylor evaluated and facilitated the development and licensure of numerous new vaccines, such as acellular pertussis, varicella, pneumococcal conjugate, human papillomavirus (HPV) influenza, zoster and all of the new-generation [idri.org]

• Abdominal Pain

  Visceral Leishmaniasis (also known as Kala-azar) The infection spreads to the liver, spleen and bone marrow causing fever, loss of appetite, weight loss and abdominal pain. This form is often fatal if untreated. [fitfortravel.nhs.uk]

  You have severe abdominal pain. Your skin or the whites of your eyes turn yellow. When should I contact my healthcare provider? Your skin has signs of infection, such as pus or swelling. Your symptoms do not get better with treatment. [drugs.com]

  Fever, weakness, abdominal pain, mucosal bleeding, and splenomegaly are the most common findings in VL. Hepatomegaly is seen in more than half of the cases. [intjinfection.com]

  Risks with CBD include: suicidal thoughts, suicide attempts, feelings of agitation, new or worsening depression, aggression and panic attacks in addition to liver injury, which can cause nausea, vomiting, abdominal pain, fatigue, anorexia, jaundice and [mdmag.com]

  Side effects were arthralgias, myalgias, itch, rash, nausea, anorexia, abdominal pain, cough and headache. [dx.doi.org]

• Hepatomegaly

  Hepatomegaly is less frequent than splenomagaly. Jaundice, edema, and ascitis are reported less frequently. [intechopen.com]

  Disfiguring lesions of the lips and nose may be a late sign of cutaneous leishmaniasis Abdominal enlargement due to splenomegaly and in some cases hepatomegaly. Extremities: Generalized lymphadenopathy may be observed in visceral leishmaniasis. [symptoma.com]

  Visceral manifestations include pronounced splenomegaly (hard, non-tender) and to a lesser extent hepatomegaly. [wynman.com]

  […] whole body Follows a chronic relapsing or progressive course Often difficult to treat Visceral leishmaniasis (VL) VL affects internal organs including the spleen, liver and lymph nodes Signs and symptoms include fever, weight loss, lymphadenopathy, hepatomegaly [dermnetnz.org]

• Ulcer

  These are primarily ulcers in their mouth and nose or on their lips. [healthline.com]

  Clinical Findings and Treatment: Cutaneous Leishmaniasis Signs and Symptoms: Cutaneous leishmaniasis (CL) is characterized by single or multiple lesions typically progress from papules to nodules to non-ulcerated dry plaques or ulcers (with raised indurated [wynman.com]

  It is often described as a wet lesion although ulcers of L major are often crusted. Chiclero’s ulcer is usually caused by L mexicana complex. [clinicaladvisor.com]

  It is characterized by lesions that range from pimples to large ulcers located on the skin of the legs, feet, hands, and face, most of which heal spontaneously after many months. [britannica.com]

• Skin Lesion

  Leishmaniasis Recidivans This term is used to define the recurrence of a skin lesion years after the initial lesion healed. [rarediseases.org]

  Symptoms of Cutaneous Leishmaniasis: Initial symptoms include skin lesions, which develop after several weeks or months after being infected, and swollen glands. The lesions – closed or open sores – can change overtime in size and appearance. [iamat.org]

  Picture of a leishmaniasis skin lesion; photo courtesy of the CDC. [emedicinehealth.com]

  Cutaneous leishmaniasis is characterized by disfiguring skin lesions that are sometimes self-healing within months or years, or become chronic. [dndi.org]

  Deletion of Arg1 in hematopoietic and endothelial cells using Tie2Cre +/− Arg1 fl/fl C57BL/6 mice abolished the expression of Arg1 in skin lesions and dLNs but did not affect development and resolution of skin lesions, parasite burden, NO production, [jimmunol.org]

• Skin Ulcer

  Cutaneous leishmaniasis Cutaneous ulcers will often heal without treatment. However, treatment can speed healing, reduce scarring, and decrease risk of further disease. Any skin ulcers that cause disfigurement may require plastic surgery. [healthline.com]

  Mucosal leishmaniasis may develop after the original skin ulcers of some forms of cutaneous leishmaniasis have been treated or have healed. Symptoms include nasal obstruction, discharge, nosebleed, and ulcers of the nose, mouth, or throat. [tripprep.com]

  Known locally as uta L. guyanensis The Guyana, Brazil Single skin ulcers, but lymphatic spread may result in widespread ulceration. Known locally as pian bois. [web.stanford.edu]

  The cutaneous symptoms are similar to those in humans (see below) and include: Skin ulcers mainly on the face Hairlessness Dandruff (squamosis) Seborrhoea Excessive long claws The viscerous form starts with the silent invasion by the Leishmania of the [lrd.spc.int]

• Skin Disease

  Parasitic Skin Diseases, Infectious Skin Diseases Antimony Sodium Gluconate Antiprotozoal Agents Antiparasitic Agents Anti-Infective Agents Schistosomicides Antiplatyhelmintic Agents Anthelmintics [clinicaltrials.gov]

  Old World cutaneous leishmaniasis is a mostly self-limiting skin disease in adults, but depending on the species, infected infants and children can develop the visceral form of the disease. [iamat.org]

  Clinical presentation depends upon the type of leishmaniasis, although there is overlap between the forms: visceral leishmaniasis fever hepatosplenomegaly skin disease may be seen cutaneous leishmaniasis (includes mucocutaneous form) ulcerating skin lesions [radiopaedia.org]

  A woman receives treatment for a tropical skin disease (Getty Images ) Syria’s healthcare system has been devastated by years of conflict. [independent.co.uk]

• Insect Bite

  These nocturnal insects bite from dusk to dawn and are often found in forests, stone and mud walls cracks, and animal burrows. They are very tiny silent flyers – they do not hum – and their bite might go unnoticed. [iamat.org]

  More on: Insect Bite Prevention Note: Bed nets, repellents, and insecticides should be purchased before traveling and can be found in hardware, camping, and military surplus stores. [cdc.gov]

  The key to prevention is insect bite avoidance. Sand flies are very small and their bites can be painless. They are most active from dusk till dawn and are commonly found in rural areas, but have also adapted to an urban environment. [travelhealthpro.org.uk]

• Epistaxis

  Bleeding episodes, especially epistaxis are frequent. The late stage of illness is often complicated by secondary bacterial infection. [intechopen.com]

  The sole presenting signs of disease could be epistaxis, ocular abnormalities, or manifestations of kidney disease without dermal abnormalities. [merckvetmanual.com]

  Head and neck: Signs of gum bleeding and epistaxis may be observable in some cases. Disfiguring lesions of the lips and nose may be a late sign of cutaneous leishmaniasis Abdominal enlargement due to splenomegaly and in some cases hepatomegaly. [symptoma.com]

  Other manifestations may include generalized lymphadenopathy; hyperpigmented skin of the forehead, abdomen, hands, and feet in light-skinned persons; skin lesions in dark-skinned persons; signs of bleeding (petechiae, epistaxis, bleeding gums); jaundice [wynman.com]

• Asthenia

  After acute debut with fever, dyspepsia, asthenia, patient subjected conventional treatment for such situations. Because of the lack of the well outcome she underwent sternal punction. [ibn.idsi.md]

  Other side effects included mild proteinuria, elevated serum creatinine, fever, asthenia, chills, arthralgia, anorexia, and myalgia ( Romero 1996 ; Llanos‐Cuentas 2007 ); intramuscular or intravenous pentamidine (isethionate or methanesulfonate) is a [dx.doi.org]

  One month after treatment, the patient developed daily vomiting, asthenia, anorexia, febrile sensation and pruritus. [scielo.isciii.es]

  Clinical manifestations Number of patients % Hepatomegaly 633 98.0 Splenomegaly 632 97.8 Fever 628 97.7 Pallor 533 82.5 Increased lymph nodes 500 77.5 Increased abdominal volume 463 71.7 Weight loss 462 71.5 Long eyelashes 454 70.3 Dry hair 450 69.7 Asthenia [intechopen.com]

  It is manifested by lymphadenopathy, hepatomegaly, splenomegaly, pallor, anemia, leukopenia, thrombocytopenia, fever, night sweats, weakness, anorexia, asthenia, cutaneous pigmentation, and weight loss, which can progress rapidly in weeks or months. [f1000research.com]

The presence of the cardinal signs mentioned above and the history of travel to endemic areas for leishmaniasis clinches the diagnosis of the disease. The following additional tests may be used to determine the presence of leishmania in a host:

• Bone marrow and splenic aspirate may be examined in the microscope to demonstrate the actual protozoan. This is the most sensitive test available for leishmaniasis. Polymerase Chain Reaction (PCR) may be implored to aid the diagnosis.
• Blood smear and nasopharyngeal swabs may demonstrate the presence of the amastigotes through Giemsa staining techniques.
• Direct Agglutination Test or ELISA test may detect the parasite very early in the course of the disease.
• Leishmanin skin test conveys a positive result after an active disease.
• Culture of Leishmania may require a specialized media.

• Normocytic Anemia

  In laboratory tests, he had normochromic normocytic anemia and elevated ESR. He was initially diagnosed with pneumonia. [intjinfection.com]

The use of antiparasitic pentavalent antimonial like sodium stibogluconate and meglumine antimonate are the mainstay in the treatment of all forms of leishmaniasis [7]. Pentavalent antimonials have cure rate of 90%-97% for leishmaniasis. However, the liposomal form of Amphoteracin B is the drug of choice for visceral leishmaniasis [8].

The oral antineoplastic drug miltefosine has been advocated to halt the proliferation of leishmania in the cutaneous tissues [9]. In India, meltifosine has become the drug of choice for visceral leishmaniasis [10]. Other treatment options available for the cutaneous disease includes: cryotherapy, reconstructive surgery, local heat therapy and topical paromomycin preparations.

The localized cutaneous forms of leishmaniasis are expected to resolve within 3 to 6 months without therapy. The disseminated cutaneous form of leishmaniasis are often associated with treatment resistance and are extremely disfiguring to the face although mortality rates remains low.

The mucocutaneous forms are more disfiguring for it attacks the mid-facial structures like the palate, lips and the nose. Mortality is evident due to the secondary bacterial infection of the respiratory system. Visceral leishmaniasis is potentially serious and lethal especially in those with poor immune resistance and poor nutritional status.

Complications

The majority of the complications in leishmaniasis is due to the relative anemia, leukopenia and thrombocytopenia in patients. The following clinical conditions are the more common complications of leishmaniasis:

• Bacteremia or septicemia
• Bacterial coinfection like pneumonia and tuberculosis
• Splenomegaly which may lead to rupture
• Uncontrolled hemorrhage
• Disfigurement of the middle face
• Edema and hyperpigmentation in the late stage
• Nasopharyngeal tissue destruction

The primary reason of leishmaniasis transmission is the eventual migration of human population to the natural habitat of sandflies in the jungle because of urban expansion to the wild. There is a close correlation with leishmaniasis and poverty, malnutrition, the unavailability of vaccines, and the limited access of first line medical care.

Persons with AIDS have a 100 fold risk of acquiring leishmaniasis in endemic areas of the globe. Old world leishmaniasis is primarily caused by Leishmania donovani endemic in China, India and Bangladesh, Leishmania tropica in the Middle East and the Mediterranean and in Africa caused by Leishmania aethiopica. The new world leishmaniasis is dominated by Leishmania brazilienses in Central and South America and Leishmania chagasi in Central and South America.

Transmission of the disease through the bite of the sandfly is the most common mode of transmission but less common routes include congenital transfer, blood transfusion, sexual intercourse and sharing of infected needles, which only occurs in endemic countries [2].

Leishmaniasis is fairly rare in the United States with sporadic cases of cutaneous leishmaniasis found in southern Texas and Oklahoma bordering Mexico [3]. During the Persian Gulf War at least 400 US service men acquired cutaneous leishmaniasis from their tour of duty [4].

Approximately 1% of US forces serving the Western Asia are infected with the Old World leishmaniasis [5]. The World Health Organization (WHO) reports that there is an annual incidence of 220,000 cases of cutaneous Leishmaniasis and 58,000 cases of visceral forms occurring worldwide [6].

Males has double the risk of the disease compared to the females due to occupational exposures to the sandfly’s habitat. The adolescent and young adults are the more susceptible group in Colombia and Afghanistan while the infant group are more prone in Iran.

Leishmania is introduced to the human skin in its flagellated form (mastigote) from the salivary glands of the sandfly. When the protozoan enters the blood stream they lose their flagella and become an amastigote where a majority are extinguished by the body’s natural defense and the minority are engulfed by the macrophages where they multiply and evolve. The fast proliferation of the leishmania species within the cell incapacitates it till it explodes and releases the active form of the parasite (promastigote) to infect other healthy cells.

They have a predisposition in infecting the reticuloendothelial cells rendering the host vulnerable to any cell mediated immunity breach. Parasitized macrophages abound the spleen and the bone marrow. Engorgement of the vascular vessels of the spleen leads to enlargement. Bone marrow becomes hyperplastic and the hematopoetic tissues are subsequently replaced by the parasitized macrophages. The disseminated cutaneous spread of leishmaniasis is due to the relative anergy of the system to immunologically react to the protozoal antigen.

Like any parasitic vector-borne disease, leishmaniasis is best prevented by the prejudicial avoidance of the sandfly’s habitat especially in endemic regions.

The early diagnosis and treatment is still the most important guiding principle in the treatment of the disease. Vaccination against leishmania seems to be a promising option but may not offer adequate protection against the visceral forms. Insect repellants must always be applied to the skin to prevent insect bites.

Leishmaniasis is a disease caused by an intracellular protozoan parasite called Leishmania spp. transmitted through the bite of a sandfly (genus Phlebotomus).

Leishmaniasis is generally divided into two categories:

• Visceral leishmaniasis or Kala-azar caused by Leishmania donovani, Leishmania chagasi and Leishmania infantum presenting as low red and white blood cell count, fever and splenomegaly
• Mucocutaneous leishmaniasis or Espundia primarily caused by Leishmania braziliensis presenting as mucocutaneous nodule or ulcers on the site of sandfly bite.

Leishmaniasis may also be conveniently classified as to geographical origin. The Old World Leishmaniasis from Asia, Africa and Middle East and the New World Leishmaniasis occurring in Central and South America [1]. Latent disease may express after 2-6 months of incubation and may present with relapse after 10 years.

Patients bitten by the Phlebotomus sandfly must submit to immediate medical therapy to circumvent the advancement of the clinical course. Any potentially disfiguring lesions in the middle face must be brought in immediately for surgical evaluation and care. A patient infected with leishmania must take absolute care not to contract secondary infections because he is categorically immune-compromised.

1. World Health Organization. Leishmaniasis: the disease and its epidemiology. Accessed April 10, 2014
2. Cardo LJ, Rentas FJ, Ketchum L, Salata J, Harman R, Melvin W, et al. Pathogen inactivation of Leishmania donovani infantum in plasma and platelet concentrates using riboflavin and ultraviolet light. Vox Sang. Feb 2006; 90(2):85-91
3. Centers for Disease Control and Prevention. Parasites home: leishmaniasis. Resources for health professionals. 
4. Magill AJ, Grogl M, Gasser RA Jr, Sun W, Oster CN. Visceral infection caused by Leishmania tropica in veterans of Operation Desert Storm. N Engl J Med. May 13 1993; 328(19):1383-7.
5. Centers for Disease Control and Prevention. Update: Cutaneous leishmaniasis in U.S. military personnel--Southwest/Central Asia, 2002-2004. MMWR Morb Mortal Wkly Rep. Apr 2 2004; 53(12):264-5.
6. Alvar J, Cañavate C, Gutiérrez-Solar B, Jiménez M, Laguna F, López-Vélez R, et al. Leishmania and human immunodeficiency virus coinfection: the first 10 years. Clin Microbiol Rev. Apr 1997; 10(2):298-319.
7. World Health Organization. Essential leishmaniasis maps: cutaneous leishmaniasis.
8. Centers for Disease Control and Prevention. Parasites home: leishmaniasis. Epidemiology & risk factors. 
9. Investigational Drug Available Directly from CDC for the Treatment of Infections with Free-Living Amebae.MMWR Morb Mortal Wkly Rep. Aug 23 2013; 62(33):666.
10. Prasad R, Kumar R, Jaiswal BP, Singh UK. Miltefosine: an oral drug for visceral leishmaniasis. Indian J Pediatr. Feb 2004; 71(2):143-4.