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.

• 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 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]

  The clinical manifestations most often found in the admission include hepatomegaly, splenomegaly, fever, and pallor. [intechopen.com]

• Fever

  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]

  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]

  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. [symptoma.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]

  Cold, Fever and Flu Treatment in Children Medications and Home Remedies Slideshow Maybe it starts with the sniffles. Maybe it starts with a cough and mild aches and pains. Maybe it’s a long day with an upset stomach. [emedicinehealth.com]

• Increased Susceptibility to Infections

  The global incidence of leishmaniasis has increased in recent years due to increased international leisure- and military-related travel, human alteration of vector habitats, and concomitant factors that increase susceptibility, such as infection with [emedicine.medscape.com]

• 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]

  […] 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]

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

• Joint Stiffness

  Secondary outcomes: Adverse effects Mild to moderate muscle and joint stiffness were experienced by 62% (13/21) participants in the low‐dose group and 58% (11/19) participants in the high‐dose group. [dx.doi.org]

• Skin Ulcer

  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]

  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]

  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]

• Night Sweats

  Other symptoms of systemic visceral leishmaniasis may include: Abdominal discomfort Fever that lasts for weeks; may come and go in cycles Night sweats Scaly, gray, dark, ashen skin Thinning hair Weight loss Your health care provider will examine you and [nlm.nih.gov]

  Adults more often have bouts of fever, night sweats, tiredness and loss of appetite. There may also be abdominal discomfort, grey discoloration of the skin and weight loss. [news-medical.net]

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.

• Albuminuria

  myalgias, anorexia, nausea, vomiting, lack of appetite, malaise, tremors, diarrhoea, fever, urticaria, headache, rash, phlebitis, mild to moderate muscle and joint stiffness, itch, cough, herpes zoster, mild leucopenia, thrombocytopenia, jaundice, albuminuria [dx.doi.org]

• Liver Enzymes Abnormal

  Patients on long-term azole therapy require routine blood tests for liver function abnormalities. [academic.oup.com]

  Injection-site dolour, nephrotoxicity, leucopenia and liver enzyme abnormalities are common adverse events. The drug is potent, with in vitro trypanocidal IC 50 values in the order of 1–10 nM. [doi.org]

  Laboratory abnormalities were limited to increases in liver enzymes in 48% (10/21) and 53% (10/19), respectively; mild leucopenia in 9.5% (2/21) and 5.3% (1/19), respectively; and electrocardiographic abnormalities in 19% (4/21) and 21% (4/19), respectively [dx.doi.org]

  including hypergammaglobulinemia, anemia, leukopenia, thrombocytopenia, hypoalbuminemia, elevated acute inflammatory markers, and liver enzyme abnormalities. [idsociety.org]

• Torsades De Pointes

  Serious toxicities like prolonged QT interval is of electrocardiogram (QTc), cardiac arrhythmias, ventricular premature beats, ventricular tachycardia, ventricular fibrillation and torsades de pointes, can occasionally occur. [dx.doi.org]

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.