Visceral Leishmaniasis

Incubation period: average is four to six months (varies from 2 weeks to 18 months)

Synonyms: Kala-azar (Indian name for "Black Disease"), Black fever/sickness, Dum dum fever

Epidemiology:

Source: http://www.who.int/leishmaniasis/leishmaniasis_maps/en/index.html

For the past 10 years, epidemics consistently reoccur in Bangladesh, India, Sudan, and Brazil, where more than 90% of the cases occur. Each year, 500,000 new cases are reported of visceral leishmaniasis (VL)and of this, 5,000 have resulted in death. Infection with L. donovani is particularly rampant in India. Unlike other countries endemic with visceral leishmaniasis, India is unique in that transmission may occur without an animal reservoir. A human reservoir and competent sandfly vector is sufficient to transmit the parasite and cause disease.

The epidemiology of visceral leishmaniasis is changing due to the increasing rate of co-infection with HIV. Spain, Italy, and Southern France are experiencing a high incidence of co-infection with HIV and VL among youth who have had previous exposure to L. infantum or use intravenous drugs. For the HIV infected individuals in Spain, the fourth most common HIV-related infection is VL. Individuals with HIV have a lower immunity to infection; thus, they are more susceptible to VL which requires a strong immunological response to contain infection.

Visceral Leishmaniasis and co-infection with HIV/AIDS:

With the spread of HIV/AIDS, co-infection with Leishmaniasis has risen to epidemic proportions. Recently, visceral leishmaniasis, a disease typically found in rural areas, is now commonly seen in urban areas among the HIV-infected population. Co-infection with Leishmania is reported in 34 countries in Africa, Asia, Europe, and South America. According to the WHO, over 70% of HIV cases in southern Europe are also co-infected with visceral leishmaniasis.

Infection with visceral leishmaniasis and HIV is particularly harmful due to the parasites' ability to suppress immunity and stimulate the replication of the HIV virus. Co-infection with visceral leishmaniasis and HIV is usually spread between individuals who share needles, usually intravenous drug users.

Currently, the WHO and UNAIDS is working to control the epidemic by setting up surveillance systems in 28 institutions worldwide. By providing common guidelines for diagnosis and computerized case report forms, the WHO and UNAIDS can continue to track the trajectory of the disease.

Source: http://www.who.int/leishmaniasis/burden/hiv_coinfection/burden_hiv_coinfection/en/

Pathogenesis:

For visceral Leishmaniasis, the pathogenesis is complex. Three species of L. Donovoni cause visceral leishmaniasis: L. donovani, L. infantum, and L. chagasi. Initially, the infection is asymptomatic. If the infection spreads, the severe symptoms of kal-azar disease become increasingly apparent. Once the species causing VL parsitize reticuloendothelial cells (RE), the disease, if left untreated, may result in a 75% to 95% mortality rate within the first two years of infection.

As the disease progresses, the spleen and liver may become enlarged with the invasion of parasites in the (RE) cells. As a consequence of infection in the bone marrow, individuals may become anemic and further destruction of red and white blood cells may occur. Although ocular complications are rare, they sometimes manifest as retinal hemorrhages, keratitis, and central retinal vein thrombosis to name a few.

Clinical Manifestations:

Photos courtesy of (L-R):pathmicro.med.sc.edu/ parasitology/blood-proto.htm, http://pubs.acs.org/cen/80th/images/, http://gsbs.utmb.edu/microbook/images/

Although VL patients may be asymptomatic or have a very mild disease burden, this form of Leishmaniasis can be the most severe form. It affects many of the internal organs leaving causing the patient extreme debilitation.

Diagnosis:

Treatment:

Drug

mechanism of action

dosing

Therapy Duration

side effects

Results

Sodium Stibogluconate (Pentostam)

*Not licensed for use in the US

Cause parasite death by inhibiting glycolytic enzymes and fatty acid oxidation

Administered intravenously or intra-muscularly

20 mg/kg body weight daily for 28 days

Coughing, headache, vomiting

Cutaneous lesions may not usually require antimonials to heal. After several weeks, the lesions tend to heal on their own.

Pentamidine

Inhibits dihydrofolate reductase and interferes with aerobic glycolysis in protozoa, also inhibits protein synthesis

intramuscular

2-4 mg/kg body weight for 10-15 days

Nausea, anorexia, dizziness, pruritus, hypotensions, pain at site of infection, occasional seizures

Because of the drug's toxicity, pentamidine is only usually used if antimonials are uneffective. Pentamidine helps heal lesions.

Allopurinol

*may be used to treat VL patients who have AIDS

Inhibits xantine oxidase and the production of uric acid

Oral, IV

20 mg/kg 3x day

Gas, nausea, vomiting, risk of renal impairment

Lesion healing

Amphotericin B (Fungizone)

*preferred treatment in India and Mediterranean because of poor response to antimonials

Causes parasite death

intravenously

Gradually increase dose to 1mg/kg lb every other day until 2-3g is given

Slightly toxic

Cutaneous lesions may not usually require antimonials to heal. After several weeks, the lesions tend to heal on their own.

Miltefosine (Impavido)

*new drug being tested

Effects cell-signaling pathways and synthesis of the cell-membrane

oral

Renal and liver toxicity, nausea, diarrhea, vomitting

According to trials, there is a risk of relapse and lower rate of success

Photos (Top-bottom): http://www.usp.org/patientSafety/newsletters/practitionerReportingNews/prn1202004-09-30.html?USP_Print , http://www.plantexusa.com/products/commercial/allopurinol.htm , http://www.noprescriptiondrugs.com/pharm253.html

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Sources:

Melby, PC. Experimental leishmaniasis in humans: review. Rev Infect Dis 1991; 13:1009.

Personal Interview. 17 May 2006. Dr. Brian Blackburn, Stanford Medical School- Infectious Diseases

http://www.cdc.gov/ncidod/dpd/parasites/leishmania/factsht_leishmania.htm

http://www.utdol.com/utd/content/topic.do?topicKey=parasite/16332

http://pathmicro.med.sc.edu/parasitology/blood-proto.htm

David, J. Petri, W. “Leishmaniasis.” Markell and Voge's Medical Parasitology . Elsevier, Inc. Ninth Edition. 2006. 127-139.