Leishmaniasis

What is Leishmaniasis?

Leishmaniasis is a disease caused by a microscopic parasite called Leishmania, usually passed on by infected sandflies. This disease is quite common across various continents, especially in tropical climates like Europe, Africa, Asia, and America. In humans, these parasites multiply inside our cells and typically cause a disease that mainly affects the skin or internal organs.

Leishmaniasis is a very old disease with records of its existence dating back thousands of years. Studies on Egyptian mummies from around 3500 to 2800 BCE revealed evidence of Leishmaniasis. Interestingly, it is believed that the disease was brought to Egypt through trade and military interactions with Nubia (now Sudan). There’s also an ancient medical document from 1500 BC that describes a potential case of skin-based leishmaniasis, referred to as “Nile Pimple.”

In the years following, skin sores resembling leishmaniasis were reported, and there were records of a disease in northern Afghanistan, now thought to have been caused by a specific type of Leishmania. The disease continued to appear in various places like Asia and the Middle East, leading to several localized names like the “Aleppo boil,” “Jericho boil,” and the “Baghdad boil.”

The breakthrough into understanding leishmaniasis came when a Scottish doctor noticed parasites present in a specific type of skin sore. However, it wasn’t until a Russian physician found similar indications that they finally identified the disease’s cause to be a type of protozoa, in 1898. Around this period, the disease was also recognized by various other names, including “dum-dum fever.” As more research uncovered different variations of the parasite, the disease was identified as being caused by Leishmania donovani and its subspecies.

A system was then created to classify the disease as either new world or old world leishmaniasis, based on the particular organisms causing the disease and where they were found.

What Causes Leishmaniasis?

Leishmaniasis is an illness caused by a specific type of single-celled organism called a protozoa, belonging to the Leishmania genus. This protozoa goes through two stages of growth: the amastigote stage, which infects certain cells in the body that eat harmful things, like bacteria or damaged cells; and the promastigote stage, where it attaches to small, hair-like structures in certain insects.

The insect that spreads this disease is the sandfly. There are several species of sandfly, but the most common ones that spread leishmaniasis are Phlebotomus and Sergentomyia, which are responsible for most cases in the Old World (Africa, Asia, and Europe), while Lutzomyia is mostly responsible for cases in the New World (the Americas).

Sandflies, which are much smaller than a small mosquito or are less than 3.5 mm in length, prefer to live in damp environments as they can easily get dehydrated. This also dictates where the disease occurs most frequently. Sandflies are most active at night and hide under rocks and in holes during the day. When a female sandfly needs a blood meal to survive, she may bite a human. During this bite, the sandfly can transmit the protozoa causing Leishmaniasis to a person.

Risk Factors and Frequency for Leishmaniasis

Leishmaniasis is a disease that is common in many regions of the world such as Asia, Middle East, Northern Africa, the Mediterranean, and South and Central America. It is present in 89 countries and each year, between 1.5 and 2 million new cases are reported. The disease can cause problems in the skin and mucous membranes or internal organs, and is responsible for approximately 70,000 deaths every year. According to a 2012 report by the World Health Organization (WHO), most cases of the disease affecting the skin and internal organs were found in specific countries.

Signs and Symptoms of Leishmaniasis

Leishmaniasis is a disease that typically manifests in three main forms: cutaneous, mucocutaneous, and visceral. Each form is caused by different organisms.

• Cutaneous leishmaniasis: This is the most common form of the disease. It can further be categorized into localized and diffuse cutaneous disease. Symptoms begin with an unnoticed bump or bumps that appear 2 to 4 weeks after infection. They then grow larger and turn into distinct ulcers with a violet border and damaged epidermis. These ulcers often heal on their own within 2 to 5 years, leaving a depressed scar. The diffuse cutaneous type can start the same way but might progress to cover the whole skin surface, often affecting the face, ears, and joints like the knees and elbows. A third of patients may have the disease spread to their nose and mouth areas. This can lead to “leonine facies”, a condition that changes a person’s facial appearance. Skin issues might further develop into widespread light-coloured patches.
• Mucocutaneous leishmaniasis: This often occurs after the resolution of cutaneous lesions and is as a result of the disease spreading through the blood or lymphatic system. Symptoms usually appear within two years after the first infection but can also take several decades. The disease mostly affects the mouth and nose areas, although ulcers can also occur in the voice box and windpipe. It does not, however, affect bony structures. Mucocutaneous leishmaniasis can become serious and life-threatening.
• Visceral leishmaniasis or kala-azar: This form of the disease affects internal organs and often comes with other symptoms such as fever, an enlarged spleen, hypergammaglobulinemia, and pancytopenia. The liver, spleen, bone marrow, or other internal organs can be directly infected. This form of the disease also peaks in the spring. After treatment, there may be some mild skin manifestations termed “post-kala-azar dermal leishmaniasis”. These skin lesions are not disfiguring and are usually temporary.

Testing for Leishmaniasis

If your doctor thinks you might have leishmaniasis, a disease caused by parasites, they’ll use a variety of tests to confirm the diagnosis. In general, the most reliable way to diagnose this condition is by examining tissue samples under a microscope. However, this method isn’t very sensitive, meaning it might miss the disease.

One way to increase sensitivity is to use the press-imprint-smear method. This method improves the chance of detecting the parasite. Other tests, like using a parasite culture tube with a special medium called Novy-MacNeal-Nicolle, could be used too, but this method is technically difficult and also not very sensitive. That said, newer micro-culture technologies have dramatically improved the sensitivity – up to 98.4% – and offer 100% specificity, meaning they are very accurate in identifying the disease.

Serologic tests look for specific immune responses to the parasite in your blood. Examples are the enzyme-linked immunosorbent assays, western blot, and the direct agglutination test. However, these tests are rarely used for leishmaniasis because the body’s immune response to the parasite is usually low, which means the tests are not very sensitive. To improve the performance of these tests, some labs use purified antigen preparations or genetically engineered antigens.

Testing for elevated levels of a certain antibody (anti-alpha-Gal IgG) in the blood has been shown to be useful in diagnosing leishmaniasis types caused by L. tropica and L. major. It might also be helpful in confirming that a treatment has worked for certain forms of the disease.

Skin tests involve injecting a small amount of the parasite’s antigens into the skin, with a reaction greater than or equal to 5mm usually considered positive for leishmaniasis. However, this test can’t tell the difference between a past or a current infection, so it’s not very useful for ongoing monitoring.

Finally, methods like Polymerase chain reaction (PCR)–which amplifies the parasite’s DNA–and nucleic acid amplification tests are being increasingly used. These tests are both sensitive and specific.

For suspected cases of systemic leishmaniasis–where the disease has spread to organs such as the spleen and liver–it can be challenging to get tissue samples. In these cases, the direct agglutination and rK39 dipstick blood tests might be more useful. The direct agglutination test’s sensitivity ranges from 97-100%, and specificity from 86% to 92%. If these tests don’t provide a clear answer, a bone marrow biopsy may be used, which is typically positive in patients with bone marrow involvement.

In summary, diagnosing leishmaniasis often depends on the resources available, as not all medical clinics or hospitals have access to all these tests.

Treatment Options for Leishmaniasis

For infectious diseases like Leishmaniasis (a disease caused by the bite of tiny sandflies), the initial steps typically focus on prevention. This includes understanding which areas are prone to the disease, being aware of sandfly activity which typically increases at night, and being cautious around animals in areas known to harbor the disease. Because sandflies are tiny, even smaller than mosquitos, you would need a bed net with very small holes, for protection while sleeping. Some people also treat their nets with permethrin (an insect repellent) to further decrease the risk of sandfly bites. In some cases, vaccinating dogs and using insecticide collars on them have also helped to reduce the spread of the disease.

Leishmaniasis may appear on the skin (cutaneous leishmaniasis or CL) and can often heal on its own over time. However, it may also create complications such as secondary infections or leave permanent scars. To prevent this, treatments may be necessary. These often involve injections of certain drugs into the lesion and medications such as miltefosine, amphotericin B, and pentamidine isethionate. Other systemic agents can be used as well. Some of these treatments may have strong side effects. For lesions that are less than 5 in number, heat or cryotherapy (use of extremely cold temperatures for treatment) can also be used.

When Leishmaniasis impacts both the skin and mucous membranes (mucocutaneous leishmaniasis), more comprehensive treatment is often needed. Certain drugs are typically recommended by the World Health Organization for this type of disease. These drugs can effectively treat the disease if administered at high doses, but lower doses are often used to minimize side effects. Other treatments such as azole therapies (a group of antifungal drugs) can also be used alone or in combination with amphotericin B, which has been proven to be effective. However, their use may be limited due to variants of the disease and potential resistance to these therapies.

Leishmaniasis that impacts the internal organs (visceral leishmaniasis) needs to be treated with specific medications, often determined by the kind of Leishmaniasis species causing the infection, as resistance to drugs can greatly differ. Overall, this disease can require a variety of treatment options based on the location and symptoms. It is important to recognize that the best treatment option can be influenced by where you live, as some drugs may work better than others based on regional differences.

What else can Leishmaniasis be?

In tropical regions, skin ulcers can be caused by a variety of conditions such as:

• Furuncular myiasis
• Staphylococcal infection
• Lepromatous leprosy (characterized by changes in facial appearance, known as leonine facies)
• Tuberculoid leprosy (leads to hypopigmented or lighter patches and plaques on the skin)
• Yaws (mainly seen at the primary stage causing ulcerative or nodular lesions on lower extremities)

What to expect with Leishmaniasis

Limited cutaneous disease often clears up on its own, depending on the body’s natural immune system strength.

When it comes to visceral disease, which affects the internal organs, death rates can vary. This depends on whether we’re looking at patients in hospitals or individuals in the wider community. According to the World Health Organization, they have tentatively determined a death rate of 10% for this type of disease.

With treatment, many people can be completely cured, with cure rates discussed in previous sections of this information. However, for patients with HIV, the death rate is significantly higher. For example, a study found that the mortality rate for HIV-positive individuals in Ethiopia was 33.6%, compared to 3.6% for HIV-negative individuals in the same country.

Despite the availability of good treatments, it’s common for patients to experience side effects from the medications, and these side effects are often severe.