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Leishmaniasis

Leishmaniasis

The Leishmaniases are diseases caused by protozoan parasites from more than 20 species belonging to the genus Leishmania. They are transmitted to humans by the bites of infected female phlebotomine sandflies. After malaria, leishmaniasis is the most dangerous parasitic infection in the world. There are three main forms of the disease: cutaneous leishmaniasis, visceral leishmaniasis or kala-azar, and mucocutaneous leishmaniasis.

Epidemiology

Leishmaniasis is found in more than 90 countries globally, but mainly in the tropics, subtropics, and southern Europe. The ecologic settings range from rain forests to deserts. Leishmaniasis is usually more common in rural than in urban areas, but it is found in the outskirts of some cities. Climate and other environmental changes have the potential to expand the geographic range of the sand fly vectors and the areas in the world where leishmaniasis is found. Leishmaniasis is found on every continent except Australia and Antarctica.

  • In the Old World (the Eastern Hemisphere), leishmaniasis is found in some parts of Asia, the Middle East, Africa (particularly in the tropical region and North Africa), and southern Europe. It is not found in Australia or the Pacific islands.
  • In the New World (the Western Hemisphere), it is found in some parts of Mexico, Central America, and South America. It is not found in Chile or Uruguay. Occasional cases of cutaneous leishmaniasis have been acquired in Texas and Oklahoma.

     • 90% of visceral leishmaniasis cases occur in Bangladesh, Brazil, India, Nepal and Sudan

     • 90% of mucocutaneos leishmaniasis occurs in Bolivia, Brazil, and Peru

     • 90% of cutaneous leishmaniasis cases occur in Afghanistan, Brazil, Iran, Peru, Saudi Arabia and Syria

the  the prevalence of leishmaniasis

Aetiology

It’s mainly linked to areas where there is 

  • Poverty
  • Malnutrition
  • Displacement
  • Poor housing
  • Illiteracy 
  • Gender discrimination
  • Immunosupression following renal transplant or HIV
  • Contamination of blood transfusion
  • Lack of resources 
  • Environmental changes,such as deforestation, building of dams, new irrigation schemes and urbanization
  • Migration of non-immune people to endemic areas.

 

The causative 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. Different species show prevalence in certain regions throughout the world.

 

Typically associated with visceral leishmaniasis is:

  • L. donovani complex with 2 species (L. donovani, L. infantum [also known as L. chagasi in the New World]).

 

    Typically associated with cutaneous leishmaniasis:

    • L. Mexicana complex with 3 main species (L. Mexicana, L. amazonensis, and L. venezuelensis)
    • L. tropica is less immunogenic and causes less inflamed slow healing sores with relapsing lesions and a tuberculoid histology
    • L. major causes the most necrosis and is the most immunogenic and allergenic cause of cutaneous leishmania
    • L. aethiopica
    • 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.

    Clinical features

    Visceral leishmaniasis (VL)

    Caused by the L. donovani complex. Following malaria, this is the worlds second most deadly parasitic infection. Typically affects small children and infants, except in HIV co-infection or India, where adults are affected as well. The incubation period ranges from months to years.

    The first sign of infection is fever +/- rigors and chills that increases overtime and its interrupted by periods of normal body temperature. This is followed in the next week by splenomegaly which can be massive , there may be a moderate hepatomegaly. Lymphadenopathy is seen in the majority of African, South american and Mediterranean patients. In advance disease the patient may develop a black (hyperpigmented), warty discoloration of the skin ( the disease derived its name from this as Kalazar means black water in Hindi) other features may include:

    • Pancytopenia with resultant increase in infection (TB, pneumonia, severe amoebic or bacillary dysentery and skin manifestation like scabies) and bleeding
    • Anaemia which can cause congestive cardiac failure
    • Retinal and gastro intestinal bleeding
    • Pedal oedema and ascites from hypoalbumineamia
    • Arthralgia
    • Burning feet
    • Abdominal pain

    Without treatment, the mortality of VL approaches 100%.

    Symptoms of Leishmaniasis

    Cutaneous leishmaniasis

    Incubation occurs over weeks to months followed by the appearance of an itchy erythematous papule. The crust may fall off evolving into a plaque or ulcer (chiclero's ulcer). New World disease usually presents with a solitary nodule, and typically causes greater disfigurement. For example parasites such as L. Mexicana may cause destruction of the pinna (Chiclero's ear).

    Old World disease is associated with multiple lesions.

    Systemic symptoms are absent. Wound progression occurs over time and may exhibit localized lymphangitic spread. Spontaneous recovery may occur.

     

    Mucocutaneous leishmaniasis

    • inital symptoms are similar to that of cutanous leishmaniasis
    • single or multpile lesions and ulcers develop at the mucosal regions (nose, mouth, throat cavities) and in the adjacent tissue
    • extensive disfiguring of the nasal septum, lips, and palate (does not include the bones)

    DDx:leprosy, TB, syphilis, yaws and cancer.

     

    Investigation

    • FBC which usually demonstrates pancytopenia (the most dominant feature)
    • Polyclonal hypergammaglobulinaemia (IgG and IgM)
    • Hypoalbumineamia
    • Demonstration of Amastigotes leishman donvani bodies is diagnostic (95% sensitivity) it can be obtained from the bone marrow, lymph nodes or the spleen. Splenic puncture gives a high yield but its risky with a potential hazard of bleeding
    • PCR is also useful as it can detects the DNA
    • ELISA for serodiagnosis
    • K39 strip test as a rapid screening test

    For cutaneous leishmaniasis a skin biopsy is used to demonstrate the infectious agents and wedge biopsies from the edge of cutaneous nodules are taken rather than the necrotic centre, where the parasite is likely to be.

    In mucocutaneous leishmaniasis parasites may be scanty, so a Leishmania skin test may be indicated.

    Although splenic puncture is the most specific diagnostic test it’s still a risky procedure so there are some contraindications:

    • Spleen barely or not palpable
    • Jaundice (a sign of possible liver dysfunction)
    • Signs of active bleeding (nose, skin, digestive, etc…). A history of recent nose bleeding without active bleeding is not a contraindication for spleen aspiration
    • Severe anaemia (Haemoglobin  < 5.5 mg/dl)
    • Pregnancy
    • Patient in very poor general condition
    • Low blood pressure
    • Uncooperative patient or caretaker
    • Lack of informed consent from patient or caretaker

    In patients with contra-indication(s) to spleen puncture, lymph node aspirates can be done, provided that enlarged lymph nodes are present.

     

    There are 3 limitations of serology testing in visceral leishmaniasis:

    1) Ab levels will remain detectable for several years after treatment, therefore relapse cannot be identified

    2) There are false +'s in healthy people with no history of the disease

    3) False -'s in HIV+ people.

     

    Differential diagnosis

    • Malaria
    • Typhoid
    • TB
    • Schistosomiasis
    • Leprosy (can mimic cutaneous)
    • Neoplastic conditions  like CML

     

    Management

    When treating a patient with leishmaniasis the following should be taken into consideration:

    • the parasite must be eradicated from the patient's  body
    • the drugs used in the treatment have serious side effects
    • nutritional support cannot be overstated
    • remain vigilant for complications

     treatment of V.L should include

    • pharmacotherapy 
    • treat co infection 
    • optimize haemoglobin and transfuse if severely anaemic
    • good hydration 
    • nutritional support

    Pentavalent antimony is the first line drug and remains as the drug of choice for the treatment of leishmaniasis.

    Sodium stibogluconate 100 mg/ml, the daily dose is 20mg /kg body weight IV or IM for 28 -30 days.

    Side effects of sodium stibogluconate are common and include

    • Arthralgia
    • Myalgia
    • Raised hepatic enzymes
    • Pancreatitis
    • ECG changes (T wave inversion and reduced amplitude)
    • Cardiotoxicity which manifests as concave ST segment elevation and ventricular arrhythmias

     

      Amphotericin B I is also used as first line drug in many countries it has a cure rate of 100%. It is used 0.75 -1.00 mg/kg for 15 – 20 doses.

      Amphotericin B has many serious side effects including

      • hepatic toxicity
      • renal toxicity
      • hypokalemia
      • thrombocytopenia

      Alternative medicines include pentamidine, miltefosine and paromomycin especially in countries like India where there is increased resistance.

      Treatment of cutaneous leishmaniasis with antimonials will heal lesions faster and prevent relapse, local dissemination, mucosal disease (usually), and transmission. Not all lesions require treatment. Old World disease tends to be self-healing, and systemic treatment is seldom used. New World lesions more often require systemic treatment. Management of cutaneous leishmaniasis is difficult to achieve and it needs patient compliance and it recurs frequently. Treatment of mucocutaneous leishmaniasis is inadequate once there is mucosal involvement, so there is a focus on early treatment of cutaneous lesions. 

      Prognosis and Prevention

      Indicators of response to treatment

      1) Disappearance of fever and improved well-being

      2) Reduction in spleen size

      3) Return in normal weight

      4) Recovery of blood counts occur

      Patients should be closely followed up for 6-12 months as some relapse following successful treatment. 

      Travel advice to avoid Leishmaniasis (from the CENTER FOR DISEASE CONTROL AND PREVENTION (CDC) website advice to travelers)

      The best way for travelers to prevent infection is to protect themselves from sand fly bites. To decrease the risk of being bitten, follow these preventive measures:

      Avoid outdoor activities, especially from dusk to dawn, when sand flies generally are the most active.

      When outdoors (or in unprotected quarters):

      • Minimize the amount of exposed (uncovered) skin. To the extent that is tolerable in the climate, wear long-sleeved shirts, long pants, and socks; and tuck your shirt into your pants. (See below about wearing insecticide-treated clothing.)
      • Apply insect repellent to exposed skin and under the ends of sleeves and pant legs. Follow the instructions on the label of the repellent. The most effective repellents generally are those that contain the chemical DEET (N,N-diethylmetatoluamide).

      When indoors:

      • Stay in well-screened or air-conditioned areas.
      • Keep in mind that sand flies are much smaller than mosquitoes and therefore can get through smaller holes.
      • Spray living/sleeping areas with an insecticide to kill insects.
      • If you are not sleeping in a well-screened or air-conditioned area, use a bed net and tuck it under your mattress. If possible, use a bed net that has been soaked in or sprayed with a pyrethroid-containing insecticide. The same treatment can be applied to screens, curtains, sheets, and clothing (clothing should be retreated after five washings).

      Summary

      • leishmaniasis is caused by the leishmania species (donvani, tropica , mexicana , major)
      • the main types are visceral ,cutenous and mucocutenous
      • the visceral type affects the reticuloendothelial system presenting with heptosplenomegaly and pancytopenia the diagnosis is best confirmed with splenic puncture or bone marrow examination
      • the cutanous type affects the skin and causes considerable disfigurement along with the mucocutenous type it can cause a nose destruction and it resembles leprosy
      • when investigating a patient with lieshmaniasis the following investigations are usefull FBC ESR , K39 STRIP TEST , BONE MARROW EXAMINATION and SPLENIC PUNCTURE
      • nonpharmacological mangement should focus on nutrition and bed rest 
      • pharmacological treatment involoves sodium stibogluconate and amphotercin B 

      References

      • Nicki R.Colledge , Brian R.Walker ,Stuart H.Ralston (2010). Davidson`s Principle & Practice of Medicine. 21sted. Edinburgh: Churchill Livingstone Elsevier. p356-361.
      • WHO. (2014). Leishmaniasis. Available: http://www.who.int/leishmaniasis/en/. Last accessed 16th february 2014.
      • CDC. (2014). Leishmaniasis. Available: http://www.cdc.gov/parasites/leishma niasis. Last accessed 16th february 2014.
      • William H. Markle, M.D., and Khaldoun Makhoul, M.D.. (2004). Cutaneous Leishmaniasis: Recognition and Treatment. Available: http://www.aafp.org/afp/2004/0315/p1455.html. Last accessed 16th february 2014.
      • Craig G Stark, MD; Chief Editor: Burke A Cunha, MD. (2013).Leishmaniasis . Available: http://emedicine.medscape.com/article/220298-overview. Last accessed 16th february 2014.
      • Stanford. (2014). Mucocutaneous Leishmaniasis. Available: http://www.stanford.edu/class/humbio103/ParaSites2006/Leishmaniasis/Mucocutaneous.htm. Last accessed 16th february 2014.
      • Ministry of Health Uganda (April 2nd 2007). THE DIAGNOSIS, TREATMENT AND PREVENTION OF VISCERAL LEISHMANIASIS IN UGANDA Guidelines for clinicians and health workers. Uganda: Ministry of Health Uganda. 56.

       

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