Causal Agent:

Leishmaniasis is a vector-borne disease that is transmitted by sandflies and caused by obligate intracellular protozoa of the genus Leishmania. Human infection is caused by about 21 of 30 species that infect mammals. These include the L. donovani complex with 3 species (L. donovani, L. infantum, and L. chagasi); the L. mexicana complex with 3 main species (L. mexicana, L. amazonensis, and L. venezuelensis); L. tropica; L. major; L. aethiopica; and the subgenus Viannia with 4 main species (L. (V.) braziliensis, L. (V.) guyanensis, L. (V.) panamensis, and L. (V.) peruviana). The different species are morphologically indistinguishable, but they can be differentiated by isoenzyme analysis, molecular methods, or monoclonal antibodies.

Life Cycle:

Leishmaniasis is transmitted by the bite of infected female phlebotomine sandflies. The sandflies inject the infective stage (i.e., promastigotes) from their proboscis during blood meals . Promastigotes that reach the puncture wound are phagocytized by macrophages and other types of mononuclear phagocytic cells. Progmastigotes transform in these cells into the tissue stage of the parasite (i.e., amastigotes) , which multiply by simple division and proceed to infect other mononuclear phagocytic cells . Parasite, host, and other factors affect whether the infection becomes symptomatic and whether cutaneous or visceral leishmaniasis results. Sandflies become infected by ingesting infected cells during blood meals ( , ). In sandflies, amastigotes transform into promastigotes, develop in the gut (in the hindgut for leishmanial organisms in the Viannia subgenus; in the midgut for organisms in the Leishmania subgenus), and migrate to the proboscis .

Geographic Distribution:
Leishmaniasis is found in parts of about 88 countries. Approximately 350 million people live in these areas. Most of the affected countries are in the tropics and subtropics. The settings in which leishmaniasis is found range from rain forests in Central and South America to deserts in West Asia. More than 90 percent of the world's cases of visceral leishmaniasis are in India, Bangladesh, Nepal, Sudan, and Brazil. Leishmaniasis is found in Mexico, Central America, and South Americafrom northern Argentina to Texas (not in Uruguay, Chile, or Canada), southern Europe (leishmaniasis is not common in travelers to southern Europe), Asia (not Southeast Asia), the Middle East, and Africa (particularly East and North Africa, with some cases elsewhere).

Clinical Features:
Human leishmanial infections can result in 2 main forms of disease, cutaneous leishmaniasis and visceral leishmaniasis (kala-azar). The factors determining the form of disease include leishmanial species, geographic location, and immune response of the host. Cutaneous leishmaniasis is characterized by one or more cutaneous lesions on areas where sandflies have fed. Persons who have cutaneous leishmaniasis have one or more sores on their skin. The sores can change in size and appearance over time. They often end up looking somewhat like a volcano, with a raised edge and central crater. A scab covers some sores. The sores can be painless or painful. Some people have swollen glands near the sores (for example, in the armpit if the sores are on the arm or hand). Persons who have visceral leishmaniasis usually have fever, weight loss, and an enlarged spleen and liver (usually the spleen is bigger than the liver). Some patients have swollen glands. Certain blood tests are abnormal. For example, patients usually have low blood counts, including a low red blood cell count (anemia), low white blood cell count, and low platelet count. Some patients develop post kalaazar dermal leishmaniasis. Visceral leishmaniasis is becoming an important opportunistic infection in areas where it coexists with HIV.

Laboratory Diagnosis:
Examination of Giemsa stained slides of the relevant tissue is still the technique most commonly used to detect the parasite. Diagnostic findings Microscopy

Isolation of the organism in culture (using for example the diphasic NNN medium) or in experimental animals (hamsters) constitutes another method of parasitilogic confirmation of the diagnosis, and in addition can provide material for further investigations (e.g., isoenzyme analysis). Antibody detection can prove useful in visceral leishmaniasis but is of limited value in cutaneous disease, where most patients do not develop a significant antibody response. In addition, cross reactivity can occur with Trypanosoma cruzi, a fact to consider when investigating Leishmania antibody response in patients who have been in Central or South America. Other diagnostic techniques exist that allow parasite detection and/or species identification using biochemical (isoenzymes), immunologic (immunoassays), and molecular (PCR) approaches. Such techniques, however, are not readily available in general diagnostic laboratories.

Treatment:
Physicians may consult CDC to obtain information on how to treat leishmaniasis. The drug sodium stibogluconate is available under an Investigational New Drug protocol from the CDC Drug Service.

Causal Agent:
The protozoan parasite, Trypanosoma cruzi, causes Chagas disease, a zoonotic disease that can be transmitted to humans by blood-sucking triatomine bugs. To see drawings of some common species of triatomine bugs found in the United States, click here and for pictures, click here.

Life Cycle:

An infected triatomine insect vector (or kissing bug) takes a blood meal and releases trypomastigotes in its feces near the site of the bite wound. Trypomastigotes enter the host through the wound or through intact mucosal membranes, such as the conjunctiva . Common triatomine vector species for trypanosomiasis belong to the genera Triatoma, Rhodnius, and Panstrongylus. Inside the host, the trypomastigotes invade cells near the site of inoculation, where they differentiate into intracellular amastigotes . The amastigotes multiply by binary fission and differentiate into trypomastigotes, and then are released into the circulation as bloodstream trypomastigotes . Trypomastigotes infect cells from a variety of tissues and transform into intracellular amastigotes in new infection sites. Clinical manifestations can result from this infective cycle. The bloodstream trypomastigotes do not replicate (different from the African trypanosomes). Replication resumes only when the parasites enter another cell or are ingested by another vector. The kissing bug becomes infected by feeding on human or animal blood that contains circulating parasites . The ingested trypomastigotes transform into epimastigotes in the vectors midgut . The parasites multiply and differentiate in the midgut and differentiate into infective metacyclic trypomastigotes in the hindgut . Trypanosoma cruzi can also be transmitted through blood transfusions, organ transplantation, transplacentally, and in laboratory accidents.

Geographic Distribution:
The Americas from the southern United States to southern Argentina. Mostly in poor, rural areas of Mexico, Central America, and South America. Chronic Chagas disease is a major health problem in many Latin American countries.

Clinical Features:
The acute phase is usually asymptomatic, but can present with manifestations that include fever, anorexia, lymphadenopathy, mild hepatosplenomegaly, and myocarditis. Romaa's sign (unilateral palpebral and periocular swelling) may appear as a result of conjunctival contamination with the vector's feces. A nodular lesion or furuncle, usually called chagoma, can appear at the site of inoculation. Most acute cases resolve over a period of a few weeks or months into an asymptomatic chronic form of the disease. The symptomatic chronic form may not occur for years or even decades after initial infection. Its manifestations include cardiomyopathy (the most serious manifestation); pathologies of the digestive tract such as megaesophagus and megacolon; and weight loss. Chronic Chagas disease and its complications can be fatal.

Laboratory Diagnosis:
Demonstration of the causal agent is the diagnostic procedure in acute Chagas disease. It almost always yields positive results, and can be achieved by: Microscopic examination: a) of fresh anticoagulated blood, or its buffy coat, for motile parasites; and b) of thin and thick blood smears stained with Giemsa, for visualization of parasites. Isolation of the agent: a) inoculation in culture with specialized media (e.g. NNN, LIT); b) inoculation into mice; and c) xenodiagnosis, where uninfected triatomine bugs are fed on the patient's blood, and their gut contents examined for parasites 4 weeks later.

Note: In certain circumstances, investigational molecular diagnostic tools, such as PCR, may be useful. Diagnostic Findings Microscopy Antibody detection

Treatment:
Medication for Chagas disease is usually effective when given during the acute phase of infection and may be indicated for patients in the chronic phase as well. The drugs of choice are benznidazole or nifurtimox (under an Investigational New Drug protocol from the CDC Drug Service). For additional information, see the recommendations on CDC's Division of Parasitic Diseases