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A Social Issue Neglected Tropical Diseases and Three Major Infectious Diseases

The Leishmaniases

< Appearance of a cutaneous leishmaniasis patient > CDC

Leishmaniasis, a disease caused by protozoan parasites of the genus Leishmania, is transmitted by the bite of a species of sand fly, a tiny flying insect. It is widely observed in more than 90 countries and territories in southern Europe or tropical and subtropical regions. More than 12 million people are currently infected, while an additional 900,000 to 1.3 million are infected every year.

Causes of Infection

Disease Agent

Protozoan parasite Leishmania

< Promastigote stage of leishmania > CDC

Vector

A species of the sand fly

< Sand fly > CDC

When a female sand fly infected with Leishmania bites people to suck up blood, promastigote of leishmania is transmitted to them. Aside from this kind of transmission (via sand fly), cases of infection via injection needles, blood transfusions, and mother-to-child infection have been reported. Infection is possible even in areas where there are no sand flies via people and goods moving from areas where leishmaniasis is epidemic.

感染経路

U.S. Centers for Disease Control and Prevention,
"Parasites - Leishmaniasis." Accessed March 19, 2014,
http://www.cdc.gov/parasites/leishmaniasis/biology.html

There are varieties of the leishmaniases distinctive to each infected region. Symptoms of infection are categorized into three types according to the variety: cutaneous leishmaniasis, mucocutaneous leishmaniasis, and visceral leishmaniasis.

Symptoms

Among the above three types of the leishmaniases, the most common is cutaneous leishmaniasis. Symptoms vary widely from no serious symptoms to death.

< Appearance of a cutaneous leishmaniasis patient > CDC

Cutaneous Leishmaniasis

This is the most common type of leishmaniasis by far. When the macrophage of a person’s skin is infected by Leishmania parasite, bumps or lumps develop in a few weeks to a few months, and they continue to grow until they become ulcers. Ulcers are accompanied by pain and, when the same areas are infected by other bacteria or when an ulcer is formed near joints, they are sometimes accompanied by acute pain. These symptoms usually disappear without any treatment, but it takes a few months to sometimes a few years for them to disappear, and it leaves scars on the skin.

 
Visceral Leishmaniasis

For this form, which is caused by infection of visceral macrophage, it takes a few months to a few years before symptoms emerge, such as fever, weight loss, and lower blood cell counts.

 
Mucocutaneous Leishmaniasis

This disease occurs when infected macrophage from cutaneous leishmaniasis (infected by a protozoa, mainly Leishmania belonging to subgenus Viannia) is transferred to the nose, mouth, or pharynx. When cutaneous leishmaniasis is untreated or poorly treated, it can develop into mucocutaneous leishmaniasis in a few years. The early symptoms include tenacious nasal congestion, nose bleeding, and discomfort in the mouth or pharynx, but it may lead to severe mucocutaneous damage, affecting patient’s appearance.

 

Diagnosis and Treatment

Diagnostic Methods

When leishmaniasis symptoms are spotted, diagnoses are made according to the symptoms, starting with a medical interview on whether the patient has been in areas where leishmaniasis is epidemic.

Cutaneous Leishmaniasis

A skin sample is taken from the infected area to verify the presence of Leishmania, using stained specimens and other methods.

Visceral Leishmaniasis

The presence of Leishmania is tested in bone marrow aspiration, the liver, or in their cultures.

 
Treatment

Mucocutaneous leishmaniasis and visceral leishmaniasis must be treated effectively. While, in principle, cutaneous leishmaniasis also calls for treatment, administration of drugs may not be necessary in some cases. In addition, different treatment are required based on the condition of the patient (pregnant woman, breast-feeding mother, child, immune compromised, or those without complications, etc.), as well as the portion of the body that is affected and the type of vector insect.

Mucocutaneous Leishmaniasis and Visceral Leishmaniasis

Treatment with Oral Medicine

Oral medicines for these infections include azole antifungal drugs and miltefosine, but their efficacy differs greatly according to the type of the Leishmania.

Treatment other than oral medicine

Mainly drugs such as pentavalent antimonials and amphotericin B are administered, generally via infusion (intravenous injection) or hypodermic injection.

Other Treatment

For cutaneous leishmaniasis that does not have a risk of developing into mucocutaneous leishmaniasis, liquid nitrogen cryotherapy or radiofrequency hyperthermia can be used.

Visceral Leishmaniasis

The types of medicines include miltefosine, pentavalent antimonials, liposome-encapsulated amphotericin B, amphotericin B deoxycholate, paromomycin sulfate, and pentamidine isethionate. Of these, the most highly recommended is the oral medicine miltefosine. It is commonly administered for 28 days. It should be noted, however, that miltefosine must not be administered to pregnant women.

 

Prevention

Currently, no vaccine or drug has been developed to prevent infection, and the most basic preventive measure is to avoid being bitten by a phlebotomus, a type of sand fly. Phlebotomus are very difficult to spot because they are tiny, about one-third the size of a mosquito, and they do not make a buzzing noise. Therefore, it is necessary to use insecticides and mosquito nets impregnated with an insecticide. The Olyset® Net developed by Sumitomo Chemical Co., Ltd. is known as such an insecticide impregnated mosquito net which is safe and has long-lasting insecticidal efficacy.

Regions at High Risk of Infection

According to data released in 2013 by the Centers for Disease Control and Prevention (CDC), this disease is widely epidemic in rural areas in more than 90 countries/regions in the tropical or subtropical and southern European regions. Specifically, there is a high risk of infection in the following countries in the eastern and western hemispheres:

[ Eastern Hemisphere ]

Asia, the Middle East, Africa (particularly tropical area and North Africa), South Europe
※ No infection has been observed in Australia and the Pacific countries.

[ Western Hemisphere ]

Mexico, Latin America
※ No infection has been observed in Chile and Uruguay.

Estimated Number of Infected People

It is estimated that about 12 million people worldwide are infected, while about 900,000 to 1.3 million are infected every year. It is also estimated that about 350 million people are susceptible to infection.

Estimated Number of Deaths

About 20,000 to 30,000 people die of leishmaniasis every year. Of the types of the leishmaniases, visceral leishmaniasis is believed to kill those infected within two years when left untreated.

Initiatives by Pharmaceutical Companies and NGOs

The number of leishmaniasis patients has grown rapidly since 1993 due to the inflow of rural populations to urban centers and other environmental changes. As of 2013, pharmaceutical companies were conducting the following activities to eliminate leishmaniasis:

Eisai

Aiming to support the development of a new vaccine for the leishmaniases and Chagas’ disease, Eisai formed a partnership with Sabin Vaccine Institute. Through this partnership, Eisai provides Sabin Vaccine Institute with vaccine adjuvant (E6020) and related information.

Gilead Sciences

Gilead Sciences is supplying amphotericin B free of charge from 2012 for the benefit of visceral leishmaniasis patients in Asia and Africa through WHO.

Eisai, AstraZeneca, Celegene, Shionogi and Takeda

The above pharmaceutical companies launched a partnership (NTD Drug Discovery Booster) with DNDi, an independent nonprofit organization. This partnership aims to jointly discover lead compounds to develop new drugs for chagas disease and visceral leishmaniasis.

References
WHO- Neglected Tropical Diseases, accessed April 2, 2015,
http://www.who.int/neglected_diseases/mediacentre/factsheet/en/
CDC- Neglected Tropical Diseases, accessed April 2, 2015,
http://www.cdc.gov/globalhealth/ntd/diseases/